Study of Novel Antiretrovirals in Participants With HIV-1

NCT ID: NCT05585307

Last Updated: 2025-05-08

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

49 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-26

Study Completion Date

2024-03-18

Brief Summary

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Master protocol: The goal of this master clinical trial study is to learn how novel antiretrovirals (medicines that stop the virus from multiplying) affect the human immunodeficiency virus-1 (HIV-1) infection in people living with HIV (PWH).

Substudy-01 (GS-US-544-5905-01) will evaluate bavtavirine in PWH.

Substudy-02 (GS-US-544-5905-02) will evaluate GS-1720 in PWH.

Substudy-03 (GS-US-544-5905-03) will evaluate GS-6212 in PWH.

Detailed Description

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This umbrella study will begin with a substudy of bavtavirine (Substudy-01), and later substudies GS-1720 (Substudy-02) and GS-6212 (Substudy-03) will be added. Substudies evaluating additional study drugs will be added in a staggered manner when relevant nonclinical and/or clinical data become available.

* Substudy-01 enrollment closed, actual enrollment is 13.
* Substudy-02 enrollment closed, actual enrollment is 28.
* Substudy-03 enrollment closed, actual enrollment is 8.

Conditions

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HIV-1-infection

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

The Substudies were conducted in parallel. However, the cohorts within the Substudies received drug assignment sequentially.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Substudy 01: Cohort 1: Bavtavirine 675 mg (High-Fat Meal)

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.

Group Type EXPERIMENTAL

Bavtavirine

Intervention Type DRUG

Administered orally

B/F/TAF

Intervention Type DRUG

Administered orally

Standard of Care (Substudy 01)

Intervention Type DRUG

Antiretroviral therapy, administered orally

Non-NNRTIs, examples: ABC/DTG/3TC; DTG plus (TAF or TDF) plus (FTC or 3TC)

Substudy 01: Cohort 2: Bavtavirine 1200 mg (Low-Fat Meal)

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 Type EXPERIMENTAL

Bavtavirine

Intervention Type DRUG

Administered orally

B/F/TAF

Intervention Type DRUG

Administered orally

Standard of Care (Substudy 01)

Intervention Type DRUG

Antiretroviral therapy, administered orally

Non-NNRTIs, examples: ABC/DTG/3TC; DTG plus (TAF or TDF) plus (FTC or 3TC)

Substudy 01: Cohort 3: Bavtavirine 900 mg (High-Fat Meal)

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 Type EXPERIMENTAL

Bavtavirine

Intervention Type DRUG

Administered orally

B/F/TAF

Intervention Type DRUG

Administered orally

Standard of Care (Substudy 01)

Intervention Type DRUG

Antiretroviral therapy, administered orally

Non-NNRTIs, examples: ABC/DTG/3TC; DTG plus (TAF or TDF) plus (FTC or 3TC)

Substudy 02: Cohort 1: GS-1720 450 mg

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 Type EXPERIMENTAL

B/F/TAF

Intervention Type DRUG

Administered orally

GS-1720

Intervention Type DRUG

Administered orally

Standard of Care (Substudy 02)

Intervention Type DRUG

Antiretroviral therapy, administered orally

Example INSTIs: DTG/ABC/3TC or DTG/3TC

Substudy 02: Cohort 2: GS-1720 150 mg

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 Type EXPERIMENTAL

B/F/TAF

Intervention Type DRUG

Administered orally

GS-1720

Intervention Type DRUG

Administered orally

Standard of Care (Substudy 02)

Intervention Type DRUG

Antiretroviral therapy, administered orally

Example INSTIs: DTG/ABC/3TC or DTG/3TC

Substudy 02: Cohort 3: GS-1720 30 mg

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 Type EXPERIMENTAL

B/F/TAF

Intervention Type DRUG

Administered orally

GS-1720

Intervention Type DRUG

Administered orally

Standard of Care (Substudy 02)

Intervention Type DRUG

Antiretroviral therapy, administered orally

Example INSTIs: DTG/ABC/3TC or DTG/3TC

Substudy 02: Cohort 4: GS-1720 900 mg

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 Type EXPERIMENTAL

B/F/TAF

Intervention Type DRUG

Administered orally

GS-1720

Intervention Type DRUG

Administered orally

Standard of Care (Substudy 02)

Intervention Type DRUG

Antiretroviral therapy, administered orally

Example INSTIs: DTG/ABC/3TC or DTG/3TC

Substudy 03: Cohort 1: GS- 6212 100 mg

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 Type EXPERIMENTAL

B/F/TAF

Intervention Type DRUG

Administered orally

GS-6212

Intervention Type DRUG

Administered orally

Standard of Care (Substudy 03)

Intervention Type DRUG

Antiretroviral therapy, administered orally

Interventions

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Bavtavirine

Administered orally

Intervention Type DRUG

B/F/TAF

Administered orally

Intervention Type DRUG

Standard of Care (Substudy 01)

Antiretroviral therapy, administered orally

Non-NNRTIs, examples: ABC/DTG/3TC; DTG plus (TAF or TDF) plus (FTC or 3TC)

Intervention Type DRUG

GS-1720

Administered orally

Intervention Type DRUG

Standard of Care (Substudy 02)

Antiretroviral therapy, administered orally

Example INSTIs: DTG/ABC/3TC or DTG/3TC

Intervention Type DRUG

GS-6212

Administered orally

Intervention Type DRUG

Standard of Care (Substudy 03)

Antiretroviral therapy, administered orally

Intervention Type DRUG

Other Intervention Names

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GS-5894 Biktarvy®

Eligibility Criteria

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Inclusion Criteria

All Substudies:

* 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.
* Antiretroviral (ARV) treatment-naive or treatment-experienced but naive to the investigational ARV drug class being investigated in the given substudy and have not received any ARV within 12 weeks of screening, including medications received for pre-exposure prophylaxis (PrEP) or postexposure prophylaxis (PEP) (note that current or prior receipt of long acting (LA) parenteral ARVs such as monoclonal antibodies (mAbs) targeting HIV-1, injectable cabotegravir (CAB), or injectable rilpivirine (RPV) is exclusionary).
* Have adequate renal function (estimated glomerular filtration rate (eGFR) ≥ 70 mL/min/1.73 m\^2)
* No clinically significant abnormalities in electrocardiogram (ECG) at screening.

Substudy-01, Substudy-02, and Substudy-03:

* Participants in substudy-01 should be willing to initiate a non-NNRTI based SOC ART on Day 11.
* Participants in substudy-02 and Substudy-03 should be willing to initiate any SOC ART on Day 11.
* Willing and able to comply with meal requirements on dosing days.

Exclusion Criteria

All Substudies:

* Known historical genotypic or phenotypic resistance to 4 major ARV classes (nucleoside reverse transcriptase inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI), integrase strand-transfer inhibitor (INSTI)).
* History of an AIDS-defining condition including present at the time of screening.
* Active, serious infections (other than HIV-1) requiring therapy and including active tuberculosis infection \< 30 days prior to randomization.
* History of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).
* Any other serious or active clinical condition or prior therapy that, in the opinion of the investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements.
* Hepatitis C virus (HCV) antibody positive and detectable HCV RNA.
* Chronic hepatitis B virus (HBV) infection, as determined by either:

* Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit, or
* Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit.
* Hepatic transaminases (aspartate aminotransferase (AST) or alanine aminotransferase (ALT)) \> 5 x upper limit of normal (ULN).
* Current alcohol or substance use judged by the investigator to potentially interfere with individual study compliance.
* Positive serum pregnancy test at screening or a positive pregnancy test prior to Day 1.
* Individuals with plan to breastfeed during the study period including the protocol-defined follow-up period.
* Requirement for ongoing therapy with or prior use of any prohibited medications listed in the protocol. Any prescription medications or over the counter medications, including herbal products, within 28 days prior to start of study drug dosing must be reviewed and approved by the sponsor, with the exception of vitamins and/or acetaminophen and/or ibuprofen.
* Any current or prior receipt of LA parenteral ARVs such as mAbs targeting HIV-1, injectable CAB, or injectable RPV, for treatment or prophylaxis (PrEP, PEP).

Substudy-01, Substudy-02, Substudy-03:

* Requirement for ongoing therapy with any prohibited medications listed in protocol.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Long Beach Education and Research Consultants,Substudy-03

Long Beach, California, United States

Site Status

Mills Clinical Research,Substudy-02

Los Angeles, California, United States

Site Status

Mills Clinical Research,Substudy-03

Los Angeles, California, United States

Site Status

Quest Clinical Research,Substudy-01

San Francisco, California, United States

Site Status

Quest Clinical Research,Substudy-02

San Francisco, California, United States

Site Status

Quest Clinical Research,Substudy-03

San Francisco, California, United States

Site Status

Yale University; School of Medicine; AIDS Program (Administrative & Study Supplies),Substudy-03

New Haven, Connecticut, United States

Site Status

Yale University,Substudy-02

New Haven, Connecticut, United States

Site Status

Washington Health Institute,Substudy-01

Washington D.C., District of Columbia, United States

Site Status

Washington Health Institute,Substudy-02

Washington D.C., District of Columbia, United States

Site Status

Washington Health Institute,Substudy-03

Washington D.C., District of Columbia, United States

Site Status

Midland Florida Clinical Research Center, LLC,Substudy-02

DeLand, Florida, United States

Site Status

Midland Florida Clinical Research, LLC,Substudy-03

DeLand, Florida, United States

Site Status

Midway Immunology and Research Center,Substudy-01

Ft. Pierce, Florida, United States

Site Status

Midway Immunology and Research Center,Substudy-02

Ft. Pierce, Florida, United States

Site Status

Midway Immunology and Research Center,Substudy-03

Ft. Pierce, Florida, United States

Site Status

Bliss Health,Substudy-02

Orlando, Florida, United States

Site Status

Bliss Health,Substudy-03

Orlando, Florida, United States

Site Status

Orlando Immunology Center,Substudy-01

Orlando, Florida, United States

Site Status

Orlando Immunology Center,Substudy-03

Orlando, Florida, United States

Site Status

Triple O Research Institute, P.A.,Substudy-01

West Palm Beach, Florida, United States

Site Status

Triple O Research Institute, P.A.,Substudy-03

West Palm Beach, Florida, United States

Site Status

Infectious Disease Specialists of Atlanta,Substudy-01

Decatur, Georgia, United States

Site Status

Indiana CTSI Clinical Research Center,Substudy-01

Indianapolis, Indiana, United States

Site Status

University of Cincinnati College of Medicine,Substudy-02

Cincinnati, Ohio, United States

Site Status

University of Cincinnati College of Medicine,Substudy-03

Cincinnati, Ohio, United States

Site Status

Central Texas Clinical Research,Substudy-01

Austin, Texas, United States

Site Status

Central Texas Clinical Research,Substudy-03

Austin, Texas, United States

Site Status

Prism Health North Texas,Substudy-02

Dallas, Texas, United States

Site Status

Prism Health North Texas,Substudy-03

Dallas, Texas, United States

Site Status

North Texas Infectious Diseases Consultant, P.A.,Substudy-02

Dallas, Texas, United States

Site Status

North Texas Infectious Diseases Consultants, P.A.,Substudy-03

Dallas, Texas, United States

Site Status

AXCES Research,Substudy-02

El Paso, Texas, United States

Site Status

AXES Research Group LLC,Substudy-03

El Paso, Texas, United States

Site Status

Therapeutic Concepts, PA,Substudy-02

Houston, Texas, United States

Site Status

Therapeutic Concepts, PA,Substudy-03

Houston, Texas, United States

Site Status

The Crofoot Research Center, Inc.,Substudy-01

Houston, Texas, United States

Site Status

MultiCare Rockwood Main Clinic- Research,Substudy-03

Spokane, Washington, United States

Site Status

Instituto Dominicano de Estudio Virologicos - IDEV,Substudy-02

Santo Domingo, , Dominican Republic

Site Status

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT),Substudy-02

Bangkok, , Thailand

Site Status

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT),Substudy-03

Bangkok, , Thailand

Site Status

Faculty of Medicine, Srinagarind Hospital, Khon Kaen University,Substudy-03

Khon Kaen, , Thailand

Site Status

Countries

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United States Dominican Republic Thailand

References

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Carl J. Fichtenbaum, Mezgebe Berhe, Jose Bordon, et al, Antiviral Activity, Safety, and Pharmacokinetics of GS-1720: A Novel Weekly Oral INSTI. Conference on Retroviruses and Opportunistic Infections, 2024, 3-6 March.

Reference Type BACKGROUND

Provided Documents

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Document Type: Study Protocol: Substudy 01 Protocol Amendment 01

View Document

Document Type: Study Protocol: Substudy 02 Protocol Amendment 02

View Document

Document Type: Study Protocol: Substudy 03 Protocol Amendment 01

View Document

Document Type: Statistical Analysis Plan: Substudy 01 Statistical Analysis Plan

View Document

Document Type: Statistical Analysis Plan: Substudy 02 Statistical Analysis Plan

View Document

Document Type: Statistical Analysis Plan: Substudy 03 Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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GS-US-544-5905

Identifier Type: -

Identifier Source: org_study_id

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