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HIV-1-infectionPhase 4ReSTARTNCT04388904

Rapid Reinitiation of a Single Tablet Antiretroviral Therapy Using Symtuza® in HIV-1 Infected Treatment-Experienced Patients Off Therapy. (ReSTART)

A Phase 4 study testing Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (FDC) in people with HIV-1-infection, run by The Crofoot Research Center, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to demonstrate the effectiveness of Symtuza® in a rapid reinitiation model of care in patients with HIV-1 infection and who are treatment-experienced but have been off of antiretroviral therapy (ART) for 12 or more weeks. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV-1-infection
What is being tested?
Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (FDC)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
1 siteUnited States
Study dates
1 Sep 2021to 5 Apr 2024
Phase
Phase 4
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

  • At least 18 years of age at screening/baseline visit.
  • Antiretroviral treatment-experienced and have not received any anti-HIV treatment within 12 weeks prior to screening.
  • Contraceptive use by men or women should be consistent with the local regulations regarding the use of contraceptive methods for subject participating in clinical studies.
  • Men must agree not to donate sperm during the study until 90 days after receiving the last dose of study drug (or longer, if dictated by local regulations).
  • Must be able to swallow whole tablets or swallow tablets cut into halves.

Who cannot join

  • Known active cryptococcal infection, active toxoplasmic encephalitis, Mycobacterium tuberculosis infection, or another AIDS-defining condition that in the judgment of the investigator would increase the risk of morbidity or mortality.
  • Known resistance to any of the components of D/C/F/TAF; subjects with known or identified FTC resistance attributed to an M184V mutation alone will be permitted to remain in the study.
  • Prior virologic failure on a DRV-containing regimen from known history or from medical records.
  • Known history of clinically relevant hepatic disease or hepatitis that in the investigator's judgment is not compatible with D/C/F/TAF.
  • Known history of severe hepatic impairment as diagnosed based on documented history of severe hepatic impairment (Child-Pugh C).
  • Known history of chronic (≥3 months) renal insufficiency, defined as having an eGFR<30 mL/min according to the MDRD formula.
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  • Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study treatment.
  • Plans to father a child while enrolled in this study or within 90 days after the last dose of study treatment.
  • Current alcohol or substance use judged by the investigator to potentially interfere with subject study adherence.
  • Known history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma.
  • Known active, severe infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy that in the judgment of the investigator would increase the risk of morbidity or mortality.
  • Any other condition or prior therapy for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the wellbeing) or that could prevent, limit, or confound the protocol-specified assessments.
  • Subject unlikely to comply with the protocol requirements based on clinical judgment.
  • Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 90 days before the planned first dose of study treatment or is currently enrolled in an investigational study.
  • Subjects receiving ongoing therapy with contraindicated, not recommended, drugs that cannot be adequately dose-adjusted, or subjects with any known allergies to the excipients of the D/C/F/TAF.
  • Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator, or employees of Johnson \& Johnson.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • The Crofoot Research Center, Inc.

    Houston, Texas, 77098

Other trials in United States

About this study

Official title: A Phase 4, Single-arm, Open-label Study to Evaluate the Efficacy and Safety of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Once Daily Fixed-dose Combination (FDC) Regimen in Antiretroviral Treatment-experienced Human Immunodeficiency Virus Type 1 (HIV-1) Infected Subjects Not Currently Receiving Any Antiretroviral Therapy.

The purpose of this study is to demonstrate the effectiveness of Symtuza® in a rapid reinitiation model of care in patients with HIV-1 infection and who are treatment-experienced but have been off of antiretroviral therapy (ART) for 12 or more weeks.

Read the detailed description

In the United States, only 49 percent of persons living with HIV infection are currently retained in care (Centers for Disease Control, 2018). Many individuals initially start antiretroviral therapy (ART) but fall out of care and discontinue treatment, only to reenter care at a later date. Gaps in care contribute to the likelihood that a patient might not have a recent viral load or CD4 count, as well as knowledge of previous ART regimens or resistance data. Furthermore, high plasma HIV-1 RNA is a major risk factor for HIV transmission, and effective ART can reduce viremia and transmission of HIV to sexual partners by more than 96% (Cohen et al., 2011; Palella et al., 1998). Thus, a secondary goal of ART is to reduce the risk of HIV transmission.

Traditional models of care have an initial period where a person is brought back into care and assessed by a healthcare provider on various factors, including HIV RNA level, genotypic/ phenotypic resistance, immune status, renal/hepatic function, and general medical comorbidities before reinitiating ART. These steps can add weeks without treatment and, in turn, delay resupression of the virus and immune system improvement, as well as continuing to contribute to the community viral load and offering more opportunities for the person to fall out of care again. (Horburg et al., 2013) This traditional model places a burden on both the patient and the healthcare system as multiple visits are required, each one a potential point where the patient can be lost again to follow-up.

A rapid reinitiation of ART for persons who have fallen out of care is a potential intervention that could improve retention rates, patient satisfaction, and clinical outcomes. Given these factors, the single-tablet regimen of D/C/F/TAF (Symtuza®) may serve as an ideal regimen for a Rapid Reinitiation model of care, combining potency, sustained efficacy, a high genetic barrier to resistance, with a well-described safety profile of the individual components, and practical, convenient dosing.

This prospective, multicenter study will follow subjects for 48 weeks with subjects either returning to the site or having a virtual visit (TeleVisit) for Weeks 2, 4, 12, 24, 36, and 48. Baseline safety labs will dictate whether the ART regimen will need to be modified but will not be required to be completed at the initiation of ART. Assessment of drug accountability, reasons for non-adherence, recording of concomitant therapies, adverse events, weight, physical examinations (complete or symptom-directed), laboratory evaluations (for efficacy and safety), and health outcome assessments will be performed from baseline onwards.

Conditions
HIV-1-infection
Being tested
Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (FDC)
Keywords
Acquired Immunodeficiency Syndrome, HIV Infections, Sexually Transmitted Diseases, Viral, Anti-Retroviral Agents, Antiviral Agents
Medical subject headings
Acquired Immunodeficiency Syndrome, HIV Infections, Sexually Transmitted Diseases, Viral

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (FDC)Drug

    Participants will receive Symtuza®. An oral tablet containing Darunavir 800 mg /Cobicistat 150 mg /Emtricitabine 200 mg /Tenofovir Alafenamide 10 mg FDC, once daily within 24 hours of the screening/ baseline visit.

Study groups in NCT04388904
Study groupRoleWhat they receive
Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (FDC)ExperimentalParticipants will receive oral tablet containing Darunavir 800 milligram (mg)/ Cobicistat 150 mg/ Emtricitabine 200 mg/ Tenofovir Alafenamide 10 mg (D/C/F/TAF) fixed-dose combination (FDC) once daily within 24 hours of the screening/baseline visit.
Receives: Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (FDC)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The proportion of subjects who have HIV-1 RNA <50 copies/mL at week 48

    The proportion of subjects who have HIV-1 RNA <50 copies/mL at week 48 as defined by the FDA snapshot analysis (ITT)

    Measured: 48 week

Secondary outcomes (19)
  1. Proportion of subjects who have HIV-1 RNA <50 copies/mL at week 48

    Proportion of subjects who have HIV-1 RNA <200 copies/mL at week 48 as defined by the per-protocol (PP) analysis set

    Measured: Week 48

  2. Proportion of subjects who have HIV-1 RNA <50 copies/mL at week 48

    Proportion of subjects who have HIV-1 RNA <200 copies/mL at week 48 as defined by the FDA snapshot analysis (ITT)

    Measured: Week 48

  3. Proportion of subjects who have HIV-1 RNA <200 copies/mL at week 24

    Proportion of subjects who have HIV-1 RNA <200 copies/mL at week 24 as defined by the FDA snapshot analysis (ITT)

    Measured: Week 24

  4. Change from baseline in HIV-1 RNA viral load

    Change from baseline in log10 HIV-1 RNA viral load at Weeks 24 and 48

    Measured: Weeks 24 and 48

  5. Change in baseline CD4 cell count

    Change in baseline CD4 cell count at Weeks 12, 24, and 48

    Measured: Weeks 12, 24, and 48

  6. Discontinuation after enrollment based on study stopping rules

    Proportion of subjects that required discontinuation after enrollment based on study stopping rules

    Measured: Week 48

  7. Discontinuation due to adverse events

    Proportion of subjects discontinuing therapy due to adverse events

    Measured: Week 48

  8. Proportion of subjects experiencing grade 3 and 4 adverse events

    Proportion of subjects experiencing grade 3 and 4 adverse events

    Measured: Week 48

  9. Proportion of subjects experiencing serious adverse events

    Proportion of subjects experiencing serious adverse events

    Measured: Week 48

  10. Proportion of subjects experiencing grade 3 and 4 laboratory abnormalities

    Proportion of subjects experiencing grade 3 and 4 laboratory abnormalities

    Measured: Week 48

  11. Proportion of subjects meeting resistance stopping rules requiring discontinuation of study drugs due baseline resistance findings

    Proportion of subjects meeting resistance stopping rules requiring discontinuation of study drugs due baseline resistance findings

    Measured: Week 48

  12. Proportion of subjects with baseline RT, INI, and PR (primary and secondary) RAMs

    Proportion of subjects with baseline RT, INI, and PR (primary and secondary) RAMs

    Measured: Week 48

  13. Proportion of subjects developing RAMs and loss of phenotypic susceptibility, when available, upon meeting PDVF

    Proportion of subjects developing RAMs and loss of phenotypic susceptibility, when available, upon meeting PDVF

    Measured: Week 48

  14. Proportion of subjects with PDVF at Week 24 and Week 48

    Proportion of subjects with PDVF at Week 24 and Week 48

    Measured: Weeks 24 and 48

  15. Proportion of subjects lost to follow-up throughout the 48 Weeks of treatment

    Proportion of subjects lost to follow-up throughout the 48 Weeks of treatment

    Measured: Week 48

  16. Proportion of subjects taking study drug at Week 48 who have a documented clinic visit with a healthcare provider within 90 days of Week 48 visit.

    Proportion of subjects taking study drug at Week 48 who have a documented clinic visit with a healthcare provider within 90 days of Week 48 visit.

    Measured: Week 48

  17. Mean total satisfaction scores on the HIVTSQs at Weeks 4, 24, and 48

    Mean total satisfaction scores on the HIVTSQs at Weeks 4, 24, and 48

    Measured: Weeks 4, 24, and 48

  18. Mean total depression scores on the PHQ-9 at baseline and Weeks 4, 24, and 48

    Mean total depression scores on the PHQ-9 at baseline and Weeks 4, 24, and 48

    Measured: Weeks 4, 24, and 48

  19. Adherence as measured by pill count at Weeks 4, 12, 24, and 48

    Adherence as measured by pill count at Weeks 4, 12, 24, and 48

    Measured: Weeks 4, 12, 24, and 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 May 2020
  2. Study start1 Sep 2021
  3. Primary completion5 Apr 2024
  4. Study completion5 Apr 2024

Resources

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 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04388904
Sponsor's protocol ID
TMC114FD2HTX4007
Acronym
ReSTART
Status last verified
Apr 2024
First submitted
12 May 2020
Last updated
26 Apr 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Mehendale S, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Wang L, Makhema J, Mills LA, de Bruyn G, Sanne I, Eron J, Gallant J, Havlir D, Swindells S, Ribaudo H, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Fleming TR; HPTN 052 Study Team. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011 Aug 11;365(6):493-505. doi: 10.1056/NEJMoa1105243. Epub 2011 Jul 18.

    PubMed 21767103
  • Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998 Mar 26;338(13):853-60. doi: 10.1056/NEJM199803263381301.

    PubMed 9516219
  • Centers for Disease Control and Prevention. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data-United States and 6 dependent areas, 2016. HIV Surveillance Supplemental Report 2018;23(No. 4). http://www.cdc.gov/hiv/library/reports/ hiv-surveillance.html. Accessed [February 4, 2020]

  • Horberg MA, Hurley LB, Silverberg MJ, Klein DB, Quesenberry CP, Mugavero MJ. Missed office visits and risk of mortality among HIV-infected subjects in a large healthcare system in the United States. AIDS Patient Care STDS. 2013 Aug;27(8):442-9. doi: 10.1089/apc.2013.0073. Epub 2013 Jul 19.

    PubMed 23869466

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (FDC) in people with HIV-1-infection, run by The Crofoot Research Center, Inc. at 1 site 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 5 inclusion and 16 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 26 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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?

The proportion of subjects who have HIV-1 RNA <50 copies/mL at week 48 (time frame: 48 week). 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 NCT04388904, which also lists 4 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 26 Apr 2024.

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