Novel Antiretroviral Therapy for HIV

No longer recruiting at 67 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Gilead Sciences

Must not be taking: Long-acting ARVs

Disqualifiers: AIDS, Active infections, Liver cirrhosis, HCV, HBV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 11 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new antiretroviral treatments to assess their impact on HIV-1 in people living with HIV. It tests three different treatments in separate substudies: bavtavirine, GS-1720 (an experimental treatment), and GS-6212. The goal is to determine how these new medicines stop the virus from multiplying. Individuals diagnosed with HIV, who have not received these investigational drugs, and have been off antiretroviral treatment for at least 12 weeks might be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive these new treatments.

Will I have to stop taking my current medications?

The trial protocol requires that any prescription or over-the-counter medications, including herbal products, taken within 28 days before starting the study drug must be reviewed and approved by the sponsor, except for vitamins, acetaminophen, and ibuprofen. This means you might need to stop or adjust some of your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found Bavtavirine to be safe when used in a treatment plan called B/F/TAF. People with HIV generally tolerated this combination well, experiencing fewer side effects compared to other HIV treatments.

For GS-1720, early information suggests it is mostly safe, with no serious side effects reported. However, a decrease in important immune cells (CD4+ T-cells) in some patients raised concerns. This issue caused some studies to pause, indicating the need for careful monitoring.

Regarding GS-6212, past research shows it has been tested without major safety concerns, but detailed safety information remains limited. Since this trial is in the early stages, it mainly focuses on checking safety and tolerance. While the treatment's safety is being tested, the full effects are still being learned.

Overall, while some safety information is available for Bavtavirine and GS-1720, GS-6212 is still in the early testing phase. Joining this trial helps to understand how safe these new treatments are for HIV. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these new antiretroviral treatments for HIV because they offer potential innovations over current options like dolutegravir-based regimens. Bavtavirine, a new active ingredient, is being tested at different doses and meal conditions, which could optimize its effectiveness and absorption. GS-1720 is another experimental drug being investigated in various doses and fasting conditions, potentially offering flexibility in dosing and improved patient adherence. Both drugs may work differently than existing treatments, potentially targeting the virus in new ways or improving convenience, thus offering hope for more effective and user-friendly HIV therapies.

What evidence suggests that this trial's treatments could be effective for HIV?

Research has shown that B/F/TAF, which participants in this trial may receive as part of their regimen, effectively treats HIV-1. Studies found that 92% of people with HIV maintained viral control after 12 months of treatment.

GS-1720, a new treatment tested in this trial, is administered to some participants in different dosages. It demonstrated stronger virus-fighting power than bictegravir, a well-known HIV drug. Considered safe, it might also serve as a long-lasting treatment.

Bavtavirine, another new drug under study in this trial, is given to participants in various dosages. Although data is limited, it works by stopping the virus from multiplying, which is crucial for managing HIV.

These treatments are being explored in this trial to provide more options for people living with HIV. ^{3 6 7 8 9}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

This trial is for adults with HIV-1 who have a certain level of viral load, CD4 cell count above 200 cells/mm^3, and good kidney function. They should be new to the drug class being tested or haven't taken any antiretrovirals in the last 12 weeks. People can't join if they've had AIDS-defining conditions, resistance to major ARV classes, hepatitis B or C infections, significant liver issues, are pregnant/breastfeeding, need prohibited medications or have serious health problems.

Inclusion Criteria

Willing and able to comply with meal requirements on dosing days

Plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) ≥ 5000 copies/mL but ≤ 400,000 copies/mL at screening

Cluster of differentiation 4 (CD4) cell count > 200 cells/mm^3 at screening

Exclusion Criteria

I am not on any medications that the study does not allow.

I have had an AIDS-defining condition.

Hepatic transaminases (aspartate aminotransferase (AST) or alanine aminotransferase (ALT)) > 5 x upper limit of normal (ULN)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of the study drug (bavtavirine, GS-1720, or GS-6212) followed by assessments and initiation of a standard antiretroviral regimen

11 days

Multiple visits for assessments and drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants continue on a standard antiretroviral regimen for additional monitoring

Up to Day 39 for Substudy 01, Day 60 for Substudy 02, and Day 25 for Substudy 03

What Are the Treatments Tested in This Trial?

Interventions

• B/F/TAF
• GS-1720
• GS-5894
• Standard of Care

Trial Overview

The study tests novel antiretrovirals GS-5894 and GS-1720 against standard HIV treatments in two substudies. Participants will start on a standard care regimen after Day 11. The aim is to see how these new drugs affect HIV-1 levels compared to usual treatments.

How Is the Trial Designed?

Group I: Substudy 03: Cohort 1: GS- 6212 100 mg Experimental Treatment 3 Interventions

Participants receive GS-6212 100 mg tablet twice daily on Days 1 through 10. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 25.

Group II: Substudy 02: Cohort 4: GS-1720 900 mg Experimental Treatment 3 Interventions

Participants receive a single dose of GS-1720 900 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.

Group III: Substudy 02: Cohort 3: GS-1720 30 mg Experimental Treatment 3 Interventions

Participants receive a single dose of GS-1720 30 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.

Group IV: Substudy 02: Cohort 2: GS-1720 150 mg Experimental Treatment 3 Interventions

Participants receive a single dose of GS-1720 150 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.

Group V: Substudy 02: Cohort 1: GS-1720 450 mg Experimental Treatment 3 Interventions

Participants receive a single dose of GS-1720 450 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.

Group VI: Substudy 01: Cohort 3: Bavtavirine 900 mg (High-Fat Meal) Experimental Treatment 3 Interventions

Participants receive bavtavirine 900 mg tablet with a high-fat meal on Days 1 and 2. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 39.

Group VII: Substudy 01: Cohort 2: Bavtavirine 1200 mg (Low-Fat Meal) Experimental Treatment 3 Interventions

Participants receive a single dose of bavtavirine 1200 mg tablet with a low-fat meal on Day 1. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 39.

Group VIII: Substudy 01: Cohort 1: Bavtavirine 675 mg (High-Fat Meal) Experimental Treatment 3 Interventions

Participants receive a single dose of bavtavirine 675 mg tablet with a high-fat meal on Day 1. After assessments on Day 11 or upon early termination (ET), the participants initiate a regimen of B/F/TAF, or an alternative standard of care (SOC) antiretroviral (ART) regimen (example INSTI + NRTIs: dolutegravir (DTG)/abacavir (ABC)/3TC or DTG/3TC) up to Day 39.

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Published Research Related to This Trial

In a study of ART-naive adults, the tenofovir alafenamide (TAF) regimen showed similar viral suppression rates to the tenofovir disoproxil fumarate (TDF) regimen at 24 weeks, but had a slightly lower rate at 48 weeks due to higher discontinuation rates in the TAF group.

TAF demonstrated significantly better renal and bone safety profiles compared to TDF, with less proteinuria and less reduction in bone mineral density, making it a promising option for initial HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate in the First Protease Inhibitor-Based Single-Tablet Regimen for Initial HIV-1 Therapy: A Randomized Phase 2 Study. Mills, A., Crofoot, G., McDonald, C., et al.[2022]

In a Phase 2 study involving 170 antiretroviral naive adults, both tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) showed high rates of virologic suppression in HIV-1 patients after 48 weeks, with 88.4% and 87.9% respectively achieving less than 50 copies of HIV RNA per milliliter.

Patients treated with TAF experienced significantly less impact on kidney function and bone mineral density compared to those treated with TDF, indicating a potentially safer profile for TAF in terms of renal and bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study. Sax, PE., Zolopa, A., Brar, I., et al.[2022]

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