HIV InfectionsPhase 1/2NCT01933594
Evaluating the Safety and Efficacy of Romidepsin in Combination With Antiretroviral Therapy in HIV-Infected Adults With Suppressed Viral Load
A Phase 1/2 study testing Romidepsin in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 sites in United States.
Trial summary
Antiretroviral therapy (ART) can reduce HIV to very low levels in the blood, but it cannot cure HIV infection because a small amount of virus remains in cells as a hidden (latent) form. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Romidepsin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 10 sitesUnited States
- Study dates
- 5 May 2014to 16 Apr 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infection, documented by any licensed rapid HIV test or HIV E/CIA test kit at any time prior to study entry \& confirmed by a licensed Western blot or a 2nd antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA
- Receiving 2 (or more) nucleoside or nucleotide reverse transcriptase inhibitors with raltegravir, dolutegravir, or efavirenz for at least 90 days prior to study entry with no intention to change for the duration of the study
- Documentation of at least 2 historical HIV-1 RNA measurements <50 copies/mL while on ART obtained by standard ultrasensitive assay. Documentation of the 1st measurement must be from a result obtained between 365-91 days, inclusive, prior to study entry. Documentation of the 2nd measurement must be from a result obtained between 730-366 days, inclusive, prior to study entry. In addition, there must be no HIV-1 RNA values ≥50 copies/mL for at least 365 days prior to study entry.
- CD4 cell count ≥300 cells/mm^3 obtained within 90-50 days prior to study entry at any US laboratory that has a CLIA certification or equivalent
- HIV-1 RNA level of <50 copies/mL obtained by standard ultrasensitive assay within 90-50 days prior to study entry
- HIV-1 RNA level of ≥0.4 copies/mL obtained by SCA within 90-50 days prior to study entry. This result must be available prior to the pre-entry visit
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- The following laboratory values obtained within 21-0 days prior to study entry by any laboratory that has a CLIA certification or equivalent
- ANC ≥1500 cells/mm^3
- Hemoglobin ≥12.0 g/dL for men \& >11.0 g/dL for women
- Platelet count ≥120,000/mm^3
- The following laboratory values obtained within 21-7 days prior to study entry by any laboratory that has a CLIA certification or equivalent
- CrCl ≥60 mL/min
- Potassium \& magnesium within normal limits
- AST (SGOT) <2.0 x ULN
- ALT (SGPT) <2.0 x ULN
- Alkaline phosphatase <2.0 x ULN
- Total bilirubin <2.5 x ULN
- HCV antibody negative result within 90-50 days prior to study entry or, for study candidates who are HCV antibody positive (based on testing performed at any time prior to study entry), a negative HCV RNA result obtained within 90-50 days prior to study entry
- Negative HBsAg result obtained within 90-50 days prior to study entry or a positive HBsAb result at any time prior to study entry
- For females of reproductive potential, negative serum or urine pregnancy test (latter with sensitivity of ≤25 mIU/mL) at the screening visit, pre-entry visit within 21-7 days prior to study entry, \& at entry prior to romidepsin infusion, by any US laboratory that has a CLIA certification or equivalent
- Female candidates of reproductive potential must refrain from participating in active attempts to become pregnant, \&, if participating in sexual activity that could lead to pregnancy, must agree to use at least 2 reliable forms of contraception that are non-estrogen based. All female participants of reproductive potential must be instructed to use contraceptives for 6 months/180 days after completing RMD or placebo infusion
- Karnofsky performance score ≥80 within 21-7 days prior to study entry
- Men and women age ≥ 18 years
- Ability \& willingness to provide written informed consent
- Investigator anticipates that a fully active alternative ART regimen could be constructed in the event of virologic failure on the current ART regimen
- HIV-1 infection, documented by any licensed rapid HIV test or HIV E/CIA test kit at any time prior to study entry \& confirmed by a licensed Western blot or a 2nd antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA
- Receiving 2 or more nucleoside or nucleotide reverse transcriptase inhibitors with raltegravir or dolutegravir for at least 90 days prior to study entry with no intention to change for the duration of the study
- Documentation of at least 2 historical HIV-1 RNA measurements <50 copies/mL while on ART obtained by standard ultrasensitive assay. Documentation of the first measurement must be from a result obtained between 365-61 days, inclusive, prior to study entry. Documentation of the second measurement must be from a result obtained between 730-366 days, inclusive, prior to study entry. In addition, there must be no HIV-1 RNA values ≥50 copies/mL for at least 365 days prior to study entry
- CD4 cell count ≥300 cells/mm^3 obtained between 36-60 days prior to study entry (screening visit) at any US laboratory that has a CLIA certification or equivalent
- HIV-1 RNA level of <50 copies/mL obtained by standard ultrasensitive assay at screening (between 36-60 days prior to study entry)
- The following laboratory values obtained at pre-entry (between 3-14 days prior to study entry) by any laboratory that has a CLIA certification or equivalent
- ANC ≥1500 cells/mm^3
- Hemoglobin ≥12.0 g/dL for men \& >11.0 g/dL for women
- Platelet count ≥120,000/mm^3
- CrCl ≥60 mL/min
- Potassium \& magnesium within normal limits
- AST (SGOT) <2.0 x ULN
- ALT (SGPT) <2.0 x ULN
- Alkaline phosphatase <2.0 x ULN
- Total bilirubin <2.5 x ULN
- HCV antibody negative result at screening (between 36-60 days prior to study entry) or, for study candidates who are HCV antibody positive (based on testing performed at any time prior to study entry), a negative HCV RNA result obtained at screening
- Negative HBsAg result obtained at screening (between 36-60 days prior to study entry) or a positive HBsAb result at any time prior to study entry
- For females of reproductive potential, negative urine pregnancy test (with a sensitivity of ≤25 mIU/mL) at screening (between 36-60 days prior to study entry), at pre-entry (between 3-14 days prior to study entry), \& at entry prior to infusion, by any US laboratory that has a CLIA certification or equivalent
- Female candidates of reproductive potential must refrain from participating in active attempts to become pregnant, \&, if participating in sexual activity that could lead to pregnancy, must agree to use at least 2 reliable forms of contraception that are non-estrogen based. All participants of reproductive potential will be instructed to use contraceptives for 6 months or 180 days after completing RMD/placebo infusion
- Karnofsky performance score ≥80 at pre-entry (between 3-14 days prior to study entry)
- Men and women age ≥ 18 years
- Ability \& willingness to provide written informed consent
- Investigator anticipates that a fully active alternative ART regimen could be constructed in the event of virologic failure on the current ART regimen
Who cannot join
- History of or current malignancy requiring cytotoxic therapy
- Bacterial, fungal, or viral infection (other than HIV) requiring systemic therapy within 30 days prior to entry
- History of or current CMV end organ disease (eg, retinitis)
- History of or current AIDS-related syndromes or symptoms that pose a perceived excessive risk for study drug-related morbidity, as determined by the investigator
- Chronic, acute, or recurrent infections that are current \& serious in the opinion of the investigator \& for which the participant has not completed at least 14 consecutive days of therapy within 30 days prior to study entry and/or is not clinically stable
- Active autoimmune disorders including but not limited to: inflammatory bowel diseases, scleroderma, severe psoriasis as determined by the investigator, systemic lupus erythematosus, rheumatoid arthritis \& optic neuritis
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- History of seizure disorders
- History of anticonvulsant use within 60 days prior to study entry
- History of MI within 6 months prior to study entry, history of QTc prolongation (defined as ECG with QTc intervals >450 ms) at any time prior to study entry, NYHA class III or IV heart failure at any time prior to study entry, or family history of prolonged QTc syndrome
- Breastfeeding
- Use of immunomodulators (eg, interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry
- Any vaccination within 30 days prior to entry or intent to receive an elective vaccination (eg, flu shot, hepatitis A or B vaccine) during the course of the study
- Intent to use cytokines (e.g., IL-2 or IL-12) during the course of the study. Prior administration of cytokines is not an exclusion criterion; however, at least 60 days between the most recent cycle of any cytokine and study entry is required
- Within 60 days prior to study entry, use of systemic azole antifungals (voriconazole, itraconazole, ketoconazole); dexamethasone; macrolide antibiotics (azithromycin, clarithromycin, erythromycin); ARVs that are inhibitors of, or are metabolized by, CYP3A4 (atazanavir, ritonavir, nelfinavir, indinavir, saquinavir, darunavir, lopinavir, rilpivirine, maraviroc); cobicistat; warfarin; nefazodone; rifamycins (rifabutin, rifampin, rifapentine); St. John's Wort; carbamazepine; phenytoin; phenobarbital; amiodarone; dofetilide; pimozide; procainamide; quinidine; sotalol; \& birth control products containing estrogen; drugs that are p-glycoprotein inhibitors; \& drugs that prolong the QTc interval with a risk of Torsades de Pointes
- Known allergy, sensitivity, or any hypersensitivity to components of RMD or its formulation
- Use of histone deacetylase inhibitors (eg, vorinostat, valproic acid) at any time prior to study entry
- Active illicit drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
- Acute or serious illness requiring systemic treatment and/or hospitalization that is not resolved within 30 days prior to entry
- Psychosocial conditions that would prevent study compliance and follow-up, as determined by the investigator
- Documented opportunistic infections within 60 days prior to entry
- History of or current malignancy requiring cytotoxic therapy
- Bacterial, fungal or viral infection (other than HIV) requiring systemic therapy within 30 days prior to entry
- History of or current CMV end organ disease (eg, retinitis)
- History of or current AIDS-related syndromes or symptoms that pose a perceived excessive risk for study drug-related morbidity, as determined by the investigator
- Chronic, acute, or recurrent infections that are current \& serious, in the opinion of the investigator, for which the participant has not completed at least 14 consecutive days of therapy within 30 days prior to study entry and/or is not clinically stable
- Active autoimmune disorders including but not limited to inflammatory bowel diseases, scleroderma, severe psoriasis as determined by the investigator, systemic lupus erythematosus, rheumatoid arthritis, \& optic neuritis
- History of seizure disorders
- History of anticonvulsant use within 60 days prior to study entry
- History of MI within 6 months prior to study entry, history of QTc prolongation (defined as ECG with QTc intervals >450 ms) at any time prior to study entry, NYHA class III or IV heart failure at any time prior to study entry, or family history of prolonged QTc syndrome
- Breastfeeding
- Use of immunomodulators (eg, interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry
- Any vaccination within 30 days prior to entry or intent to receive an elective vaccination (eg, flu shot, hepatitis A or B vaccine) during the course of the study
- Intent to use cytokines (eg, IL-2 or IL-12) during the course of the study
- Within 60 days prior to study entry, use of systemic azole antifungals (voriconazole, itraconazole, ketoconazole), dexamethasone, macrolide antibiotics (azithromycin, clarithromycin, erythromycin), antiretrovirals that are inhibitors of, or are metabolized by CYP3A4 (atazanavir, ritonavir, nelfinavir, indinavir, saquinavir, darunavir, lopinavir, rilpivirine, maraviroc), cobicistat, warfarin, nefazodone, rifamycins (rifabutin, rifampin, rifapentine), St. John's Wort, carbamazepine, phenytoin, phenobarbital, amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, \& birth control products containing estrogen, drugs that are p-glycoprotein inhibitors, \& drugs that prolong the QTc interval with a risk of Torsades de Pointes
- Known allergy/sensitivity or any hypersensitivity to components of RMD or its formulation
- Use of histone deacetylase inhibitors (eg, vorinostat, valproic acid) at any time prior to study entry
- Active illicit drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
- Acute or serious illness requiring systemic treatment and/or hospitalization that is not resolved within 30 days prior to entry
- Psychosocial conditions that would prevent study compliance \& follow-up as determined by the investigator
- Documented opportunistic infections within 60 days prior to entry
- Use of any of the medications listed in the Prohibited Medications table in the protocol
- See the protocol for Inclusion and Exclusion Criteria for Cohort 4, Steps 2, 3, and 4.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
University of Colorado Hospital CRS
Aurora, Colorado, 80045
Alabama CRS
Birmingham, Alabama, 35294
Massachusetts General Hospital CRS (MGH CRS)
Boston, Massachusetts, 02114
Chapel Hill CRS
Chapel Hill, North Carolina, 27599
Ohio State University CRS
Columbus, Ohio, 43210
UCLA CARE Center CRS
Los Angeles, California, 90035
Penn Therapeutics, CRS
Philadelphia, Pennsylvania, 19104
University of Pittsburgh CRS
Pittsburgh, Pennsylvania, 15213
University of Rochester Adult HIV Therapeutic Strategies Network CRS
Rochester, New York, 14642
University of Washington AIDS CRS
Seattle, Washington, 98104-9929
About this study
Official title: A Phase I/II Study of Romidepsin in HIV-Infected Adults With Suppressed Viremia on Antiretroviral Therapy to Assess Safety, Tolerability, and Activation of HIV-1 Expression
Antiretroviral therapy (ART) can reduce HIV to very low levels in the blood, but it cannot cure HIV infection because a small amount of virus remains in cells as a hidden (latent) form. The purpose of this study was to evaluate the safety and efficacy of single dose and multiple dose administration of romidepsin (RMD) in HIV-infected adults.
Read the detailed description
A major challenge in eradicating HIV-1 infection is the persistence of virus in long-lived cells, such as latently infected memory CD4 T cells. One approach for eliminating the HIV-1 reservoir is to activate viral replication in these latently infected CD4 T cells by targeting cellular mechanisms that repress proviral transcription. Histone deacetylase inhibitors (HDACis), such as RMD, induce HIV-1 expression by increasing acetylation and facilitating transcriptional activation of HIV-1. RMD administered in combination with ART may serve as an important component of a strategy to eradicate the HIV-1 latent reservoir. The purpose of this study was to evaluate the safety and efficacy of single dose and multiple dose administration of RMD in HIV-infected adults.
Participants were sequentially enrolled into four cohorts and randomly assigned to receive either RMD or placebo. The cohorts differed in the dose of RMD given. Participants in Cohorts 1, 2, and 3 had one intravenous (IV) infusion of RMD or placebo at Day 0. Participants in Cohort 4 had four IV infusions of RMD or placebo at Days 0, 14, 28, and 42.
For participants in Cohorts 1, 2, and 3, study duration was 4 weeks. For participants in Cohort 4, study duration was a minimum of 24 weeks and a maximum of 48 weeks.
Participants attended several study visits, which could include a physical examination, blood and urine collection, pharmacokinetic (PK) sampling, and an electrocardiogram (ECG).
- Conditions
- HIV Infections
- Being tested
- Romidepsin, Placebo for Romidepsin
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RomidepsinDrug
Also called RMD, Istodax
RMD administered over 4 hours via an intravenous (IV) catheter.
Placebo for RomidepsinDrug
Also called 0.9% NaCl, 0.9% sodium chloride
Placebo for RMD administered over 4 hours via an IV catheter.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1-Arm 1A (Romidepsin) | Experimental | Participants in Cohort 1, Arm 1A received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of Romidepsin was 0.5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). Receives: Drug: Romidepsin |
| Cohort 1-Arm 1B (Placebo for Romidepsin) | Placebo comparator | Participants in Cohort 1, Arm 1B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of sodium chloride for injection placebo was 0.5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). Receives: Drug: Placebo for Romidepsin |
| Cohort 2-Arm 2A (Romidepsin) | Experimental | Participants in Cohort 2, Arm 2A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of Romidepsin was 2 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). Receives: Drug: Romidepsin |
| Cohort 2-Arm 2B (Placebo for Romidepsin) | Placebo comparator | Participants in Cohort 2, Arm 2B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of sodium chloride for injection placebo was 2 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). Receives: Drug: Placebo for Romidepsin |
| Cohort 3-Arm 3A (Romidepsin) | Experimental | Participants in Cohort 3, Arm 3A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of Romidepsin was 5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). Receives: Drug: Romidepsin |
| Cohort 3-Arm 3B (Placebo for Romidepsin) | Placebo comparator | Participants in Cohort 3, Arm 3B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of sodium chloride for injection placebo was 5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). Receives: Drug: Placebo for Romidepsin |
| Cohort 4-Arm 4A (Romidepsin) | Experimental | Participants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits. Dose of Romidepsin was 5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). Receives: Drug: Romidepsin |
| Cohort 4-Arm 4B (Placebo for Romidepsin) | Placebo comparator | Participants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits. Dose of sodium chloride for injection placebo was 5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). Receives: Drug: Placebo for Romidepsin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants With Grade 3 or Higher Adverse Events (AEs) in Cohorts 1-3 Romidepsin Arms
Proportion of participants with Grade 3 or higher adverse events (AEs) in Cohorts 1-3 Romidepsin Arms, including signs/symptoms, lab toxicities, and /or clinical events probably, possibly, or definitely related to study treatment (as judged by the core team, blinded to treatment arm). The DAIDS AE Grading Table (Version 1.0) was used.
Measured: Measured from the time of Romidepsin administration (at entry) until 28 days after the administration
Proportion of Participants With Grade 3 or Higher Adverse Events (AEs) in Cohort 4 Romidepsin Arm
Proportion of participants with Grade 3 or Higher Adverse Events (AEs) in Cohort 4 Romidepsin Arm, including signs/symptoms, lab toxicities, and /or clinical events probably, possibly, or definitely related to study treatment (as judged by the core team, blinded to treatment arm). The DAIDS AE Grading Table (Version 1.0) was used.
Measured: Measured from the time of the first Romidepsin administration through 28 days after the last administration (at day 42)
Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohorts 1-3
Baseline is defined as the average of the pre-entry and entry values. Hour 24/48 is defined as the average of values at 24 and 48 hours after the single administration of Romidepsin or placebo (at study entry).
Change was calculated as the value at hour 24/48 minus the value at baseline.
Measured: Pre-entry, entry, 24 and 48 hours after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohort 4
Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) minus the value at baseline.
Measured: Pre-entry, entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)
Change From Baseline in Cell-associated HIV-1 RNA Levels in Resting CD4 T-cells in Cohorts 1-3
Baseline is defined as the pre-entry value. Change was calculated as the value at 24 hours after administration of Romidepsin or placebo (at entry) minus the value at baseline.
Measured: Pre-entry and 24 hours after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Cell-associated HIV-1 RNA Levels in PBMCs in Cohort 4
Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) minus the value at baseline.
Measured: Pre-entry, entry and 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)
Secondary outcomes (33)
Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohorts 1-3
Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 6 hours, 12 hours, 7 days, 14 days and 28 days after administration of Romidepsin or placebo (at entry) minus the value at baseline.
Measured: Pre-entry, entry, 6 hours, 12 hours, 7 days, 14 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohort 4
Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 72 hours after the second administration of Romidepsin or placebo (at day 14) minus the value at baseline.
Measured: Pre-entry, entry and 72 hours after the second administration of Romidepsin or placebo (at day 14)
Change From Baseline in Cell-associated HIV-1 RNA Levels in Resting CD4 T Cells in Cohorts 1-3
Baseline is defined as the pre-entry value. Change was calculated as the value at 14 days after administration of Romidepsin or placebo (at entry) minus the value at baseline.
Measured: Pre-entry and 14 days after the administration of RMD or placebo (at entry)
Change From Baseline in Cell-associated HIV-1 RNA Levels in PBMCs in Cohort 4
Baseline is defined as the pre-entry value. Change was calculated as the value at 72 hours after the second administration of Romidepsin or placebo (at day 14) minus the value at baseline.
Measured: Pre-entry and 72 hours after the second administration of Romidepsin or placebo (at day 14)
Change From Baseline in Histone Acetylation (Median FITC Ac-Histone) in CD3+ Cells in Cohorts 1-3
Baseline is defined as the value at Hour 0, right before the single administration of Romidepsin or placebo.
Change was calculated as the value at 24 hours after administration of Romidepsin or placebo (at entry) minus the value at baseline.
Median Fluorescent Intensity (MFI) data describes a shift in the expression of a fluorescently labeled marker on a population of cells. The reported MFI is an arbitrary value dependent on the voltage applied to the corresponding flow cytometer detector.
Measured: Hour 0 and 24 hours after the single administration of RMD or placebo (at entry)
Change From Baseline in Histone Acetylation in (Median FITC Ac-histone) in CD3+ Cells in Cohort 4
Baseline is defined as the value right before the first administration of Romidepsin or placebo (at entry).
Change was calculated as the value at 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration minus the value at baseline.
Median Fluorescent Intensity (MFI) data describes a shift in the expression of a fluorescently labeled marker on a population of cells. The reported MFI is an arbitrary value dependent on the voltage applied to the corresponding flow cytometer detector.
Measured: Entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42), and 72 hours after the second administration (at day 14)
Change From Baseline in Total HIV-1 DNA in Resting or Total CD4 T Cells in Cohorts 1-3
Baseline is defined as the pre-entry value. Change was calculated as the value at 24 hours and 14 days after administration of Romidepsin or placebo (at entry) minus the value at baseline.
Measured: Pre-entry, 24 hours and 14 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Total HIV-1 DNA in PBMCs in Cohort 4
Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration minus the value at baseline.
Measured: Pre-entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration (at day 14)
PK Parameters for Romidepsin and Co-administered Antiretroviral Drugs (Efavirenz, Dolutegravir, or Raltegravir) in Cohorts 1-3
Hour 0 is right before the single administration of Romidepsin or placebo (at entry).
Hour 4 is at the completion of Romidepsin or placebo administration. Hours 6, 12 and 24 are 2, 8 and 20 hours after the completion of Romidepsin or placebo administration.
PK concentration (ng/mL) for Romidepsin at hours 0, 4, 6, 12 and 24. PK concentration (ng/mL) for co-administered antiretroviral drugs (Efavirenz [EFV], Dolutegravir [DTG], or Raltegravir [RAL]) at hours 0 and 24.
Measured: At hours 0, 4, 6, 12 and 24
PK Parameters for Romidepsin and Co-administered Antiretroviral Drugs (Dolutegravir or Raltegravi) in Cohort 4
PK concentration (ng/mL) for Romidepsin pre and post the third and fourth administrations of Romidepsin or placebo.
PK concentration (ng/mL) for co-administered antiretroviral drugs (Dolutegravir [DTG], or Raltegravir [RAL]) 24 hours after the third and fourth administrations of Romidepsin or placebo.
Measured: Pre, post and 24 hours after the third and fourth administrations of Romidepsin or placebo (at days 28 and 42)
HIV-1 RNA Levels in Cohorts 1-3
HIV-1 RNA levels at 7 days after the single administration of Romidepsin or placebo (at entry)
Measured: 7 days after the administration of Romidepsin or placebo (at entry)
HIV-1 RNA Levels in Cohort 4
HIV-1 RNA levels at 7 days after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)
Measured: 7 days after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)
Number of Participants With Reported Grade 2-4 AEs in Cohorts 1-3
Number of participants with reported grade 2-4 adverse events including signs/symptoms, lab toxicities, and clinical events that are at least possibly related to study treatment. The DAIDS AE Grading Table (Version 1.0) was used.
Measured: Measured from study entry to off study
Number of Participants With Reported Grade 2-4 AEs in Cohort 4
Number of participants with reported grade 2-4 adverse events including signs/symptoms, lab toxicities, and clinical events that are at least possibly related to study treatment. The DAIDS AE Grading Table (Version 1.0) was used.
Measured: Measured from study entry to off study
Change From Baseline in CD4+ and CD8+ T Cell Percent in Cohorts 1-3
Change in CD4+ and CD8+T cell percent from baseline to after the single administration of Romidepsin or placebo
Measured: Measured through participant's last study visit
Change From Baseline in CD4+ T Cell Percent in Cohort 4
Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 24 hours post each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 2, 5, 10 and 18 weeks post the fourth administration minus the value at baseline
Measured: Pre-entry, entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42), and 2, 5, 10 and 18 weeks after the fourth administration (at day 42)
Change From Baseline in CD8+ T Cell Percent in Cohort 4
Change in CD8+ T cell percent from baseline to after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)
Measured: Measured through 28 days after the single administration of RMD or placebo (at entry, and days 14, 28 and 42)
Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD4+ T-cells) in Cohorts 1-3
Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).
Change was calculated as the value at 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo minus the value at baseline.
Measured: Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD8+ T-cells) in Cohorts 1-3
Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).
Change was calculated as the value at 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo minus the value at baseline.
Measured: Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD4+ T-cells) in Cohorts 1-3
Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).
Change was calculated as the value at 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo minus the value at baseline.
Measured: Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD8+ T-cells) in Cohorts 1-3
Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).
Change was calculated as the value at 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo minus the value at baseline.
Measured: Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD4+ T-cells) in Cohort 4
Baseline is defined as the average of the two pre-entry values. Change was calculated as the value at 24 hours post first and fourth administration of Romidepsin or placebo (at entry and day 42) and 10 weeks post the fourth administration (at day 42) minus the value at baseline.
Measured: Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at entry and day 42), and 10 weeks after the fourth administration (at day 42)
Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD8+ T-cells) in Cohort 4
Baseline is defined as the average of the two pre-entry values. Change was calculated as the value at 24 hours post first and fourth administration of Romidepsin or placebo (at entry and day 42) and 10 weeks post the fourth administration (at day 42) minus the value at baseline.
Measured: Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at entry and day 42), and 10 weeks after the fourth administration (at day 42)
Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD4+ T-cells) in Cohort 4
Baseline is defined as the average of the two pre-entry values. Change was calculated as the value at 24 hours post first and fourth administration of Romidepsin or placebo (at etnry and day 42) and 10 weeks post the fourth administration (at day 42) minus the value at baseline.
Measured: Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at etnry and day 42), and 10 weeks after the fourth administration (at day 42)
Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD8+ T-cells) in Cohort 4
Baseline is defined as the average of the two pre-entry values. Change was calculated as the value at 24 hours post first and fourth administration of Romidepsin or placebo (at etnry and day 42) and 10 weeks post the fourth administration (at day 42) minus the value at baseline.
Measured: Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at etnry and day 42), and 10 weeks after the fourth administration (at day 42
Change From Baseline in Percentage of CD4+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohorts 1-3
Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).
Change was calculated as the value at 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry) minus the value at baseline.
Measured: Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Percentage of CD8+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohorts 1-3
Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).
Change was calculated as the value at 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry) minus the value at baseline.
Measured: Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Percentage of CD4+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohort 4
Baseline is defined as the average of the two pre-entry values. Change was calculated as the value at 24 hours post first and fourth administration of Romidepsin or placebo (at entry and day 42) and 10 weeks post the fourth administration (at day 42) minus the value at baseline.
Measured: Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at entry and day 42), and 10 weeks after the fourth administration (at day 42)
Change From Baseline in Percentage of CD8+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohort 4
Baseline is defined as the average of the two pre-entry values. Change was calculated as the value at 24 hours post first and fourth administration of Romidepsin or placebo (at entry and day 42) and 10 weeks post the fourth administration (at day 42) minus the value at baseline.
Measured: Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at entry and day 42), and 10 weeks after the fourth administration (at day 42)
Change From Baseline in PTEF-b Phosphorylation (pNFKB+% and pS175%) in CD4+ T-cells in Cohorts 1-3
Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).
Change was calculated as the value at 24 hours after the single administration of Romidepsin or placebo (at entry) minus the value at baseline.
Measured: Hour 0 and 24 hours after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in PTEF-b Phosphorylation (pNFKB+% and pS175%) in CD8+ T-cells in Cohorts 1-3
Baseline is defined as the value at hour 0, where hour 0 is right before the single administration of Romidepsin or placebo (at entry).
Change was calculated as the value at 24 hours after the single administration of Romidepsin or placebo (at entry) minus the value at baseline.
Measured: Hour 0 and 24 hours after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in PTEF-b Phosphorylation (pNFKB+%) in CD4+ T-cells in Cohort 4
Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration (at day 14) minus the value at baseline.
Measured: Pre-entry, entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration (at day 14)
Change From Baseline in PTEF-b Phosphorylation (pS175+%) in CD4+ T-cells in Cohort 4
Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration (at day 14) minus the value at baseline.
Measured: Pre-entry, entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration (at day 14)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2013 (estimated)
- Study start5 May 2014
- Primary completion16 Apr 2018
- Study completion16 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- John Mellors, MD, Study chair, University of PittsburghDeborah McMahon, MD, Study chair, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01933594
- Sponsor's protocol ID
- A5315
- Other IDs
- 11892, ACTG 5315
- Status last verified
- Oct 2021
- First submitted
- 28 Aug 2013
- Last updated
- 1 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ylisastigui L, Archin NM, Lehrman G, Bosch RJ, Margolis DM. Coaxing HIV-1 from resting CD4 T cells: histone deacetylase inhibition allows latent viral expression. AIDS. 2004 May 21;18(8):1101-8. doi: 10.1097/00002030-200405210-00003.
PubMed 15166525Klimek VM, Fircanis S, Maslak P, Guernah I, Baum M, Wu N, Panageas K, Wright JJ, Pandolfi PP, Nimer SD. Tolerability, pharmacodynamics, and pharmacokinetics studies of depsipeptide (romidepsin) in patients with acute myelogenous leukemia or advanced myelodysplastic syndromes. Clin Cancer Res. 2008 Feb 1;14(3):826-32. doi: 10.1158/1078-0432.CCR-07-0318.
PubMed 18245545McMahon DK, Zheng L, Cyktor JC, Aga E, Macatangay BJ, Godfrey C, Para M, Mitsuyasu RT, Hesselgesser J, Dragavon J, Dobrowolski C, Karn J, Acosta EP, Gandhi RT, Mellors JW. A Phase 1/2 Randomized, Placebo-Controlled Trial of Romidespin in Persons With HIV-1 on Suppressive Antiretroviral Therapy. J Infect Dis. 2021 Aug 16;224(4):648-656. doi: 10.1093/infdis/jiaa777.
PubMed 34398236
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Romidepsin in HIV-Infected Adults With Suppressed Viremia on Antiretroviral Therapy to Assess Safety, Tolerability, and Activation of HIV-1 Expression
- ClinicalTrials.gov ID
- NCT01933594
- Acronym / sponsor ID
- A5315
- Conditions
- HIV Infections
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 5 May 2014 (actual)
- Primary completion
- 16 Apr 2018 (actual)
- Study completion
- 16 Apr 2018 (actual)
- First posted
- 2 Sep 2013 (estimated)
- Results
- Posted 23 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Antiretroviral therapy (ART) can reduce HIV to very low levels in the blood, but it cannot cure HIV infection because a small amount of virus remains in cells as a hidden (latent) form. The purpose of this study was to evaluate the safety and efficacy of single dose and multiple dose administration of romidepsin (RMD) in HIV-infected adults.
Detailed description
A major challenge in eradicating HIV-1 infection is the persistence of virus in long-lived cells, such as latently infected memory CD4 T cells. One approach for eliminating the HIV-1 reservoir is to activate viral replication in these latently infected CD4 T cells by targeting cellular mechanisms that repress proviral transcription. Histone deacetylase inhibitors (HDACis), such as RMD, induce HIV-1 expression by increasing acetylation and facilitating transcriptional activation of HIV-1. RMD administered in combination with ART may serve as an important component of a strategy to eradicate the HIV-1 latent reservoir. The purpose of this study was to evaluate the safety and efficacy of single dose and multiple dose administration of RMD in HIV-infected adults.
Participants were sequentially enrolled into four cohorts and randomly assigned to receive either RMD or placebo. The cohorts differed in the dose of RMD given. Participants in Cohorts 1, 2, and 3 had one intravenous (IV) infusion of RMD or placebo at Day 0. Participants in Cohort 4 had four IV infusions of RMD or placebo at Days 0, 14, 28, and 42.
For participants in Cohorts 1, 2, and 3, study duration was 4 weeks. For participants in Cohort 4, study duration was a minimum of 24 weeks and a maximum of 48 weeks.
Participants attended several study visits, which could include a physical examination, blood and urine collection, pharmacokinetic (PK) sampling, and an electrocardiogram (ECG).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Cohort 1-Arm 1A (Romidepsin) | Experimental | Drug: RomidepsinParticipants in Cohort 1, Arm 1A received Romidepsin intravenously (IV) over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of Romidepsin was 0.5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). |
| Cohort 1-Arm 1B (Placebo for Romidepsin) | Placebo comparator | Drug: Placebo for RomidepsinParticipants in Cohort 1, Arm 1B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of sodium chloride for injection placebo was 0.5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). |
| Cohort 2-Arm 2A (Romidepsin) | Experimental | Drug: RomidepsinParticipants in Cohort 2, Arm 2A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of Romidepsin was 2 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). |
| Cohort 2-Arm 2B (Placebo for Romidepsin) | Placebo comparator | Drug: Placebo for RomidepsinParticipants in Cohort 2, Arm 2B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of sodium chloride for injection placebo was 2 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). |
| Cohort 3-Arm 3A (Romidepsin) | Experimental | Drug: RomidepsinParticipants in Cohort 3, Arm 3A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of Romidepsin was 5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). |
| Cohort 3-Arm 3B (Placebo for Romidepsin) | Placebo comparator | Drug: Placebo for RomidepsinParticipants in Cohort 3, Arm 3B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0 study visit. Dose of sodium chloride for injection placebo was 5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). |
| Cohort 4-Arm 4A (Romidepsin) | Experimental | Drug: RomidepsinParticipants in Cohort 4, Arm 4A received Romidepsin IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits. Dose of Romidepsin was 5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). |
| Cohort 4-Arm 4B (Placebo for Romidepsin) | Placebo comparator | Drug: Placebo for RomidepsinParticipants in Cohort 4, Arm 4B received 0.9% sodium chloride for injection IV over 4 hours (beginning at Hour 0) at the Day 0, 14, 28, and 42 study visits. Dose of sodium chloride for injection placebo was 5 mg/m^2, with total dose based on the participant's body surface area (determined by participant's height and weight). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (48 listed)
- HIV-1 infection, documented by any licensed rapid HIV test or HIV E/CIA test kit at any time prior to study entry \& confirmed by a licensed Western blot or a 2nd antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA
- Receiving 2 (or more) nucleoside or nucleotide reverse transcriptase inhibitors with raltegravir, dolutegravir, or efavirenz for at least 90 days prior to study entry with no intention to change for the duration of the study
- Documentation of at least 2 historical HIV-1 RNA measurements <50 copies/mL while on ART obtained by standard ultrasensitive assay. Documentation of the 1st measurement must be from a result obtained between 365-91 days, inclusive, prior to study entry. Documentation of the 2nd measurement must be from a result obtained between 730-366 days, inclusive, prior to study entry. In addition, there must be no HIV-1 RNA values ≥50 copies/mL for at least 365 days prior to study entry.
- CD4 cell count ≥300 cells/mm^3 obtained within 90-50 days prior to study entry at any US laboratory that has a CLIA certification or equivalent
- HIV-1 RNA level of <50 copies/mL obtained by standard ultrasensitive assay within 90-50 days prior to study entry
Key exclusion criteria (42 listed)
- History of or current malignancy requiring cytotoxic therapy
- Bacterial, fungal, or viral infection (other than HIV) requiring systemic therapy within 30 days prior to entry
- History of or current CMV end organ disease (eg, retinitis)
- History of or current AIDS-related syndromes or symptoms that pose a perceived excessive risk for study drug-related morbidity, as determined by the investigator
- Chronic, acute, or recurrent infections that are current \& serious in the opinion of the investigator \& for which the participant has not completed at least 14 consecutive days of therapy within 30 days prior to study entry and/or is not clinically stable
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RomidepsinAlso: RMD, IstodaxRMD administered over 4 hours via an intravenous (IV) catheter. | Drug | Cohort 1-Arm 1A (Romidepsin), Cohort 2-Arm 2A (Romidepsin), Cohort 3-Arm 3A (Romidepsin), Cohort 4-Arm 4A (Romidepsin) |
| Placebo for RomidepsinAlso: 0.9% NaCl, 0.9% sodium chloridePlacebo for RMD administered over 4 hours via an IV catheter. | Drug | Cohort 1-Arm 1B (Placebo for Romidepsin), Cohort 2-Arm 2B (Placebo for Romidepsin), Cohort 3-Arm 3B (Placebo for Romidepsin), Cohort 4-Arm 4B (Placebo for Romidepsin) |
Primary outcome
Proportion of Participants With Grade 3 or Higher Adverse Events (AEs) in Cohorts 1-3 Romidepsin Arms
Time frame: Measured from the time of Romidepsin administration (at entry) until 28 days after the administration
Proportion of participants with Grade 3 or higher adverse events (AEs) in Cohorts 1-3 Romidepsin Arms, including signs/symptoms, lab toxicities, and /or clinical events probably, possibly, or definitely related to study treatment (as judged by the core team, blinded to treatment arm). The DAIDS AE Grading Table (Version 1.0) was used.
Proportion of Participants With Grade 3 or Higher Adverse Events (AEs) in Cohort 4 Romidepsin Arm
Time frame: Measured from the time of the first Romidepsin administration through 28 days after the last administration (at day 42)
Proportion of participants with Grade 3 or Higher Adverse Events (AEs) in Cohort 4 Romidepsin Arm, including signs/symptoms, lab toxicities, and /or clinical events probably, possibly, or definitely related to study treatment (as judged by the core team, blinded to treatment arm). The DAIDS AE Grading Table (Version 1.0) was used.
Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohorts 1-3
Time frame: Pre-entry, entry, 24 and 48 hours after the single administration of Romidepsin or placebo (at entry)
Baseline is defined as the average of the pre-entry and entry values. Hour 24/48 is defined as the average of values at 24 and 48 hours after the single administration of Romidepsin or placebo (at study entry). Change was calculated as the value at hour 24/48 minus the value at baseline.
Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohort 4
Time frame: Pre-entry, entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)
Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) minus the value at baseline.
Change From Baseline in Cell-associated HIV-1 RNA Levels in Resting CD4 T-cells in Cohorts 1-3
Time frame: Pre-entry and 24 hours after the single administration of Romidepsin or placebo (at entry)
Baseline is defined as the pre-entry value. Change was calculated as the value at 24 hours after administration of Romidepsin or placebo (at entry) minus the value at baseline.
Change From Baseline in Cell-associated HIV-1 RNA Levels in PBMCs in Cohort 4
Time frame: Pre-entry, entry and 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)
Baseline is defined as the average of the pre-entry and entry values. Change was calculated as the value at 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) minus the value at baseline.
33 secondary outcomes
Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohorts 1-3
Time frame: Pre-entry, entry, 6 hours, 12 hours, 7 days, 14 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Plasma HIV-1 RNA Levels as Detected by Single Copy Assay in Cohort 4
Time frame: Pre-entry, entry and 72 hours after the second administration of Romidepsin or placebo (at day 14)
Change From Baseline in Cell-associated HIV-1 RNA Levels in Resting CD4 T Cells in Cohorts 1-3
Time frame: Pre-entry and 14 days after the administration of RMD or placebo (at entry)
Change From Baseline in Cell-associated HIV-1 RNA Levels in PBMCs in Cohort 4
Time frame: Pre-entry and 72 hours after the second administration of Romidepsin or placebo (at day 14)
Change From Baseline in Histone Acetylation (Median FITC Ac-Histone) in CD3+ Cells in Cohorts 1-3
Time frame: Hour 0 and 24 hours after the single administration of RMD or placebo (at entry)
Change From Baseline in Histone Acetylation in (Median FITC Ac-histone) in CD3+ Cells in Cohort 4
Time frame: Entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42), and 72 hours after the second administration (at day 14)
Change From Baseline in Total HIV-1 DNA in Resting or Total CD4 T Cells in Cohorts 1-3
Time frame: Pre-entry, 24 hours and 14 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Total HIV-1 DNA in PBMCs in Cohort 4
Time frame: Pre-entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration (at day 14)
PK Parameters for Romidepsin and Co-administered Antiretroviral Drugs (Efavirenz, Dolutegravir, or Raltegravir) in Cohorts 1-3
Time frame: At hours 0, 4, 6, 12 and 24
PK Parameters for Romidepsin and Co-administered Antiretroviral Drugs (Dolutegravir or Raltegravi) in Cohort 4
Time frame: Pre, post and 24 hours after the third and fourth administrations of Romidepsin or placebo (at days 28 and 42)
HIV-1 RNA Levels in Cohorts 1-3
Time frame: 7 days after the administration of Romidepsin or placebo (at entry)
HIV-1 RNA Levels in Cohort 4
Time frame: 7 days after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42)
Number of Participants With Reported Grade 2-4 AEs in Cohorts 1-3
Time frame: Measured from study entry to off study
Number of Participants With Reported Grade 2-4 AEs in Cohort 4
Time frame: Measured from study entry to off study
Change From Baseline in CD4+ and CD8+ T Cell Percent in Cohorts 1-3
Time frame: Measured through participant's last study visit
Change From Baseline in CD4+ T Cell Percent in Cohort 4
Time frame: Pre-entry, entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42), and 2, 5, 10 and 18 weeks after the fourth administration (at day 42)
Change From Baseline in CD8+ T Cell Percent in Cohort 4
Time frame: Measured through 28 days after the single administration of RMD or placebo (at entry, and days 14, 28 and 42)
Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD4+ T-cells) in Cohorts 1-3
Time frame: Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD8+ T-cells) in Cohorts 1-3
Time frame: Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD4+ T-cells) in Cohorts 1-3
Time frame: Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD8+ T-cells) in Cohorts 1-3
Time frame: Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD4+ T-cells) in Cohort 4
Time frame: Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at entry and day 42), and 10 weeks after the fourth administration (at day 42)
Change From Baseline in Cellular Markers of Immune Activation (CD38/HLA-DR Expression on CD8+ T-cells) in Cohort 4
Time frame: Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at entry and day 42), and 10 weeks after the fourth administration (at day 42)
Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD4+ T-cells) in Cohort 4
Time frame: Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at etnry and day 42), and 10 weeks after the fourth administration (at day 42)
Change From Baseline in Cellular Markers of Immune Activation (CD69/CD25 Expression on CD8+ T-cells) in Cohort 4
Time frame: Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at etnry and day 42), and 10 weeks after the fourth administration (at day 42
Change From Baseline in Percentage of CD4+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohorts 1-3
Time frame: Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Percentage of CD8+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohorts 1-3
Time frame: Hour 0 and 48 hours, 7 days and 28 days after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in Percentage of CD4+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohort 4
Time frame: Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at entry and day 42), and 10 weeks after the fourth administration (at day 42)
Change From Baseline in Percentage of CD8+ T-cells Expressing Annexin V and/or 7 Amino-actinomycin D (7-AAD) in Cohort 4
Time frame: Pre-entry, 24 hours after the first and fourth administration of Romidepsin or placebo (at entry and day 42), and 10 weeks after the fourth administration (at day 42)
Change From Baseline in PTEF-b Phosphorylation (pNFKB+% and pS175%) in CD4+ T-cells in Cohorts 1-3
Time frame: Hour 0 and 24 hours after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in PTEF-b Phosphorylation (pNFKB+% and pS175%) in CD8+ T-cells in Cohorts 1-3
Time frame: Hour 0 and 24 hours after the single administration of Romidepsin or placebo (at entry)
Change From Baseline in PTEF-b Phosphorylation (pNFKB+%) in CD4+ T-cells in Cohort 4
Time frame: Pre-entry, entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration (at day 14)
Change From Baseline in PTEF-b Phosphorylation (pS175+%) in CD4+ T-cells in Cohort 4
Time frame: Pre-entry, entry, 24 hours after each administration of Romidepsin or placebo (at entry, and days 14, 28 and 42) and 72 hours after the second administration (at day 14)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15166525Ylisastigui L, Archin NM, Lehrman G, Bosch RJ, Margolis DM. Coaxing HIV-1 from resting CD4 T cells: histone deacetylase inhibition allows latent viral expression. AIDS. 2004 May 21;18(8):1101-8. doi: 10.1097/00002030-200405210-00003.
- Background: PubMed 18245545Klimek VM, Fircanis S, Maslak P, Guernah I, Baum M, Wu N, Panageas K, Wright JJ, Pandolfi PP, Nimer SD. Tolerability, pharmacodynamics, and pharmacokinetics studies of depsipeptide (romidepsin) in patients with acute myelogenous leukemia or advanced myelodysplastic syndromes. Clin Cancer Res. 2008 Feb 1;14(3):826-32. doi: 10.1158/1078-0432.CCR-07-0318.
- Derived from this study: PubMed 34398236McMahon DK, Zheng L, Cyktor JC, Aga E, Macatangay BJ, Godfrey C, Para M, Mitsuyasu RT, Hesselgesser J, Dragavon J, Dobrowolski C, Karn J, Acosta EP, Gandhi RT, Mellors JW. A Phase 1/2 Randomized, Placebo-Controlled Trial of Romidespin in Persons With HIV-1 on Suppressive Antiretroviral Therapy. J Infect Dis. 2021 Aug 16;224(4):648-656. doi: 10.1093/infdis/jiaa777.
- DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014. Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Mellors, MD study chair
University of Pittsburgh
Deborah McMahon, MD study chair
University of Pittsburgh
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Romidepsin in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 48 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants With Grade 3 or Higher Adverse Events (AEs) in Cohorts 1-3 Romidepsin Arms (time frame: Measured from the time of Romidepsin administration (at entry) until 28 days after the administration). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01933594, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.