HivPhase 2eCLEARNCT03041012
Early Administration of Romidepsin and 3BNC117 in Treatment-naïve HIV Patients Starting ART
A Phase 2 study testing Romidepsin, 3BNC117 and Antiretrovirals in people with Hiv, run by Aarhus University Hospital at 7 sites in 2 countries.
Trial summary
To evaluate the effect of early viral reactivation by latency reversing agents (LRA) and/or administration of potent broadly neutralizing antibodies (bNAb) on the size of the latent HIV-1 reservoir in treatment naïve HIV-1 patients initiating antiretroviral therapy (ART) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hiv
- What is being tested?
- Romidepsin, 3BNC117 and Antiretrovirals
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 20 Jan 2017to 30 Dec 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Documented HIV-1 infection
- CD4+ T cell count >200/µL on last visit prior to study entry
- ART naïve
- Able to give informed consent
Who cannot join
- Any significant acute medical illness (not including primary HIV infection) in the past 8 weeks
- Any evidence of an active AIDS-defining opportunistic infection
- Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy
- The following laboratory values at screening, but the values can be repeated within the screening period, but test results must be available before baseline (day 0) and checked for eligibility:
- Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN)
- Serum total bilirubin ≥3 ULN
Show all 27Show fewer
- Estimated glomerular filtration rate (eGFR) ≤60 mL/min (based on serum creatinine or other appropriate validated markers)
- Platelet count ≤100 x10^9/L
- Absolute neutrophil count ≤1x10^9/L
- Serum potassium, magnesium, phosphorus outside ≥1.5 ULN/LLN
- Total calcium (corrected for serum albumin) or ionized calcium ≥1.5 ULN/LLN
- Hepatitis B or C infection as indicated by the presence of hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood
- ECG at screening that shows QTc >450 ms when calculated using the Fridericia formula from either lead V3 or V4 [86]
- Use of:
- Warfarin or warfarin-derivatives
- HDACi
- An agent definitely or possibly associated with effects on QT intervals within 2 weeks of screening
- Drugs that induce or inhibit CYP3A4 or P-gp
- History of:
- Clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for Torsades de pointes (e.g. heart failure)
- Malignancy or transplantation, including skin cancers or Kaposi sarcoma
- Diabetes mellitus
- Receipt of strong immunosuppressive or systemic chemotherapeutic agents within 28 days prior to study entry
- Known resistance to >2 classes of ART
- Known hypersensitivity to the components of romidepsin, 3BNC117 or their analogues
- Women who are pregnant or breastfeeding, or with a positive pregnancy test during screening or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of non-estrogen containing contraceptions (according to the Danish Medicines Agency guidelines) to avoid pregnancy for the 3 week study period and 4 weeks after study treatment or until undetectable plasma HIV-1 RNA using standard assays
- Males or females who are unwilling or unable to use barrier contraception during sexual intercourse for the 3-week study period, and 4 weeks after study treatment or until undetectable plasma HIV-1 RNA using standard assays
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
Denmark5 sites
Department of Infectious Diseases
Aalborg
Dept. of Infectious Diseases, Aarhus University Hospital
Aarhus, 8200
Department of Infectious Diseases
Copenhagen
Department of Infectious Diseases
Hvidovre
Department of Infectious Diseases
Odense
United Kingdom2 sites
Guy's and St Thomas'
London
Imperial College Healthcare NHS Trust
London
About this study
Official title: Early Administration of Latency Reversing Therapy and Broadly Neutralizing Antibodies to Limit the Establishment of the HIV-1 Reservoir During Initiation of Antiretroviral Treatment - a Randomized Controlled Trial
To evaluate the effect of early viral reactivation by latency reversing agents (LRA) and/or administration of potent broadly neutralizing antibodies (bNAb) on the size of the latent HIV-1 reservoir in treatment naïve HIV-1 patients initiating antiretroviral therapy (ART)
Read the detailed description
The study will be conducted among ART naïve HIV-1-infected patients.
Subjects will continue ART while receiving LRA romidepsin and/or bNAb 3BNC117.
- Conditions
- Hiv
- Being tested
- Romidepsin, 3BNC117, Antiretrovirals
- Keywords
- HIV-1, Latency Reversal Agent, Immunotherapy
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RomidepsinDrug
Also called Istodax
5mg/m2 romidepsin will be administered IV on days 10, 17, and 24 after initiating ART
3BNC117Drug
Also called Broadly neutralizing antibody
30 mg/kg 3BNC117 will be administered IV on day 7 and 21 after initiating ART
AntiretroviralsDrug
Also called ART
Combination antiretroviral therapy
| Study group | Role | What they receive |
|---|---|---|
| antiretrovirals | Placebo comparator | Standard of care Receives: Drug: Antiretrovirals |
| antiretrovirals + romidepsin | Active comparator | Standard of care + LRA Receives: Drug: Romidepsin; Drug: Antiretrovirals |
| antiretrovirals + 3BNC117 | Active comparator | Standard of care + bNAb Receives: Drug: 3BNC117; Drug: Antiretrovirals |
| antiretrovirals + romidepsin + 3BNC117 | Active comparator | Standard of care + LRA + bNAb Receives: Drug: Romidepsin; Drug: 3BNC117; Drug: Antiretrovirals |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma HIV RNA kinetics
Time to undetectable (<20 c/mL)
Measured: 3 months
Quantification of the size of the proviral HIV reservoir
Copies of total HIV-1 DNA per 10⁶ CD4+ T cells as measured by digital droplet PCR
Measured: 1 year
Time to viral rebound during ATI
Days from stopping ART to plasma HIV RNA >5,000 on two consecutive measurements
Measured: 12 weeks
Secondary outcomes (7)
Incidence of treatment emerging events (Safety and tolerability)
Frequence and severity of adverse events (AE), adverse reactions (AR), serious adverse events (SAE), serious adverse reactions (SAR) and suspected unexpected serious adverse reactions (SUSAR).
Measured: 1 year
Quantification of the intact proviral DNA
Intact HIV-1 DNA in CD4+ T cells (copies per million cells) as measured by dd-PCR.
Measured: 1 year
Quantification of HIV mRNA and/or p24 positive cells
Frequency of mRNA/p24 postive per 1 million CD4+ T cells by FISH-flow
Measured: 30 days from study entry
Immune reconstitution
Absolute CD4+ and CD8+ T cell count
Measured: 1 year
Analytic treatment interruption (ATI) study
Time to first plasma HIV RNA >5000 c/mL
Measured: 64 weeks
Impact of pre-ART virus sensitivity to 3BNC117 on ATI outcomes
3BNC117 sensitivity determined by PhenoSense and/or HIV env sequencing
Measured: Baseline and at viral rebound
T cell mediated HIV specific immunity
T cell immunity as determined by the HIV AIM assay
Measured: First of 365 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2017 (estimated)
- Study start20 Jan 2017
- Primary completion20 Aug 2021
- Study completion30 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HivStudies of the same condition, open and under way.
- More trials run by Aarhus University HospitalThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Hvidovre University Hospital, Odense University Hospital, Aalborg University Hospital, Herning Hospital, Hammersmith Hospitals NHS Trust, St Mary's Hospital, London
- Responsible party
- Sponsor
- Investigators
- Ole S Søgaard, MD PhD, Principal investigator, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03041012
- Sponsor's protocol ID
- eCLEAR-001
- Other IDs
- 2015-002234-53, 2015
- Acronym
- eCLEAR
- Status last verified
- Apr 2025
- First submitted
- 20 Jan 2017
- Last updated
- 18 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual deidentified participant data (including data dictionaries) will be shared following the publication of the primary and secondary endpoints as outlined in this protocol. Data to be shared includes deidentified data points in published, peer-reviewed articles. Additional, related documents will also be available (study protocol, informed consent form). Data will become available following publication with no planned end date.
Publications
Gunst JD, Pahus MH, Rosas-Umbert M, Lu IN, Benfield T, Nielsen H, Johansen IS, Mohey R, Ostergaard L, Klastrup V, Khan M, Schleimann MH, Olesen R, Stovring H, Denton PW, Kinloch NN, Copertino DC, Ward AR, Alberto WDC, Nielsen SD, Puertas MC, Ramos V, Reeves JD, Petropoulos CJ, Martinez-Picado J, Brumme ZL, Jones RB, Fox J, Tolstrup M, Nussenzweig MC, Caskey M, Fidler S, Sogaard OS. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial. Nat Med. 2022 Nov;28(11):2424-2435. doi: 10.1038/s41591-022-02023-7. Epub 2022 Oct 17.
PubMed 36253609
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Administration of Latency Reversing Therapy and Broadly Neutralizing Antibodies to Limit the Establishment of the HIV-1 Reservoir During Initiation of Antiretroviral Treatment - a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03041012
- Acronym / sponsor ID
- eCLEAR / eCLEAR-001
- Conditions
- Hiv
- Keywords
- HIV-1, Latency Reversal Agent, Immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Aarhus University HospitalUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Hvidovre University Hospital, Odense University Hospital, Aalborg University Hospital, Herning Hospital, Hammersmith Hospitals NHS Trust, St Mary's Hospital, London
- Study start
- 20 Jan 2017 (actual)
- Primary completion
- 20 Aug 2021 (actual)
- Study completion
- 30 Dec 2022 (actual)
- First posted
- 2 Feb 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the effect of early viral reactivation by latency reversing agents (LRA) and/or administration of potent broadly neutralizing antibodies (bNAb) on the size of the latent HIV-1 reservoir in treatment naïve HIV-1 patients initiating antiretroviral therapy (ART)
Detailed description
The study will be conducted among ART naïve HIV-1-infected patients.
Subjects will continue ART while receiving LRA romidepsin and/or bNAb 3BNC117.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| antiretrovirals | Placebo comparator | Drug: AntiretroviralsStandard of care |
| antiretrovirals + romidepsin | Active comparator | Drug: Romidepsin, Drug: AntiretroviralsStandard of care + LRA |
| antiretrovirals + 3BNC117 | Active comparator | Drug: 3BNC117, Drug: AntiretroviralsStandard of care + bNAb |
| antiretrovirals + romidepsin + 3BNC117 | Active comparator | Drug: Romidepsin, Drug: 3BNC117, Drug: AntiretroviralsStandard of care + LRA + bNAb |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Documented HIV-1 infection
- CD4+ T cell count >200/µL on last visit prior to study entry
- ART naïve
- Able to give informed consent
Key exclusion criteria (27 listed)
- Any significant acute medical illness (not including primary HIV infection) in the past 8 weeks
- Any evidence of an active AIDS-defining opportunistic infection
- Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy
- The following laboratory values at screening, but the values can be repeated within the screening period, but test results must be available before baseline (day 0) and checked for eligibility:
- ECG at screening that shows QTc >450 ms when calculated using the Fridericia formula from either lead V3 or V4 [86]
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: Istodax5mg/m2 romidepsin will be administered IV on days 10, 17, and 24 after initiating ART | Drug | antiretrovirals + romidepsin, antiretrovirals + romidepsin + 3BNC117 |
| 3BNC117Also: Broadly neutralizing antibody30 mg/kg 3BNC117 will be administered IV on day 7 and 21 after initiating ART | Drug | antiretrovirals + 3BNC117, antiretrovirals + romidepsin + 3BNC117 |
| AntiretroviralsAlso: ARTCombination antiretroviral therapy | Drug | antiretrovirals, antiretrovirals + 3BNC117, antiretrovirals + romidepsin, antiretrovirals + romidepsin + 3BNC117 |
Primary outcome
Plasma HIV RNA kinetics
Time frame: 3 months
Time to undetectable (<20 c/mL)
Quantification of the size of the proviral HIV reservoir
Time frame: 1 year
Copies of total HIV-1 DNA per 10⁶ CD4+ T cells as measured by digital droplet PCR
Time to viral rebound during ATI
Time frame: 12 weeks
Days from stopping ART to plasma HIV RNA >5,000 on two consecutive measurements
7 secondary outcomes
Incidence of treatment emerging events (Safety and tolerability)
Time frame: 1 year
Quantification of the intact proviral DNA
Time frame: 1 year
Quantification of HIV mRNA and/or p24 positive cells
Time frame: 30 days from study entry
Immune reconstitution
Time frame: 1 year
Analytic treatment interruption (ATI) study
Time frame: 64 weeks
Impact of pre-ART virus sensitivity to 3BNC117 on ATI outcomes
Time frame: Baseline and at viral rebound
T cell mediated HIV specific immunity
Time frame: First of 365 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2025.
- Derived from this study: PubMed 36253609Gunst JD, Pahus MH, Rosas-Umbert M, Lu IN, Benfield T, Nielsen H, Johansen IS, Mohey R, Ostergaard L, Klastrup V, Khan M, Schleimann MH, Olesen R, Stovring H, Denton PW, Kinloch NN, Copertino DC, Ward AR, Alberto WDC, Nielsen SD, Puertas MC, Ramos V, Reeves JD, Petropoulos CJ, Martinez-Picado J, Brumme ZL, Jones RB, Fox J, Tolstrup M, Nussenzweig MC, Caskey M, Fidler S, Sogaard OS. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial. Nat Med. 2022 Nov;28(11):2424-2435. doi: 10.1038/s41591-022-02023-7. Epub 2022 Oct 17.
- Individual participant dataSharing planned: Yes. Individual deidentified participant data (including data dictionaries) will be shared following the publication of the primary and secondary endpoints as outlined in this protocol. Data to be shared includes deidentified data points in published, peer-reviewed articles. Additional, related documents will also be available (study protocol, informed consent form). Data will become available following publication with no planned end date.
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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.
Ole S Søgaard, MD PhD principal investigator
Aarhus University Hospital
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Romidepsin, 3BNC117 and Antiretrovirals in people with Hiv, run by Aarhus University Hospital at 7 sites in 2 countries.
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 4 inclusion and 27 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 18 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Denmark, United Kingdom. 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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Plasma HIV RNA kinetics (time frame: 3 months). The study lists 3 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 NCT03041012, which also lists 1 linked publication.
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 18 Apr 2025.