Study of Novel Antiretrovirals in Participants With HIV-1

NCT05585307 | Completed Phase 1 Results FDA Drug

• 1 other identifier: GS-US-544-5905
• Study Type: interventional
• Target: 49
• Locations: 3 countries
• Sites: 42

Brief Summary

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.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (1)

• Substudies 01, 02 and 03: Change From Baseline in Plasma Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) (log10 Copies/mL) at Day 11 Relative to Historical Placebo Data

  Baseline, Day 11

Secondary Outcomes (20)

• Substudies 01, 02 and 03: Change From Baseline in Plasma HIV-1 RNA (log10 Copies/mL) at Day 8 Relative to Historical Placebo Data

  Baseline, Day 8

• Substudies 01, 02 and 03: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)

  First dose up to last dose (Substudy 01: Up to Day 39; Substudy 02: Up to Day 60; Substudy 03: Up to Day 25)

• Substudies 01, 02 and 03: Percentage of Participants With Graded Laboratory Abnormalities

  First dose up to last dose (Substudy 01: Up to Day 39; Substudy 02: Up to Day 60; Substudy 03: Up to Day 25)

• Substudy 01: Pharmacokinetic (PK) Parameter: Cmax of Bavtavirine

  Cohorts 1, 2 and 3 (Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, and 12 hours postdose); Cohort 3: Day 2: Predose, 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose

• Substudy 01: PK Parameter: AUC of Bavtavirine

  Day 1 up to Day 11

Study Arms (8)

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

EXPERIMENTAL

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.

Drug: Bavtavirine; Drug: B/F/TAF; Drug: Standard of Care (Substudy 01)

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

EXPERIMENTAL

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.

Drug: Bavtavirine; Drug: B/F/TAF; Drug: Standard of Care (Substudy 01)

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

EXPERIMENTAL

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.

Drug: Bavtavirine; Drug: B/F/TAF; Drug: Standard of Care (Substudy 01)

Substudy 02: Cohort 1: GS-1720 450 mg

EXPERIMENTAL

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.

Drug: B/F/TAF; Drug: GS-1720; Drug: Standard of Care (Substudy 02)

Substudy 02: Cohort 2: GS-1720 150 mg

EXPERIMENTAL

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.

Drug: B/F/TAF; Drug: GS-1720; Drug: Standard of Care (Substudy 02)

Substudy 02: Cohort 3: GS-1720 30 mg

EXPERIMENTAL

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.

Drug: B/F/TAF; Drug: GS-1720; Drug: Standard of Care (Substudy 02)

Substudy 02: Cohort 4: GS-1720 900 mg

EXPERIMENTAL

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.

Drug: B/F/TAF; Drug: GS-1720; Drug: Standard of Care (Substudy 02)

Substudy 03: Cohort 1: GS- 6212 100 mg

EXPERIMENTAL

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.

Drug: B/F/TAF; Drug: GS-6212; Drug: Standard of Care (Substudy 03)

Interventions

Bavtavirine DRUG

Administered orally

Also known as: GS-5894

Substudy 01: Cohort 1: Bavtavirine 675 mg (High-Fat Meal); Substudy 01: Cohort 2: Bavtavirine 1200 mg (Low-Fat Meal); Substudy 01: Cohort 3: Bavtavirine 900 mg (High-Fat Meal)

B/F/TAF DRUG

Administered orally

Also known as: Biktarvy®

Substudy 01: Cohort 1: Bavtavirine 675 mg (High-Fat Meal); Substudy 01: Cohort 2: Bavtavirine 1200 mg (Low-Fat Meal); Substudy 01: Cohort 3: Bavtavirine 900 mg (High-Fat Meal); Substudy 02: Cohort 1: GS-1720 450 mg; Substudy 02: Cohort 2: GS-1720 150 mg; Substudy 02: Cohort 3: GS-1720 30 mg; Substudy 02: Cohort 4: GS-1720 900 mg; Substudy 03: Cohort 1: GS- 6212 100 mg

Standard of Care (Substudy 01) DRUG

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

Substudy 01: Cohort 1: Bavtavirine 675 mg (High-Fat Meal); Substudy 01: Cohort 2: Bavtavirine 1200 mg (Low-Fat Meal); Substudy 01: Cohort 3: Bavtavirine 900 mg (High-Fat Meal)

GS-1720 DRUG

Administered orally

Substudy 02: Cohort 1: GS-1720 450 mg; Substudy 02: Cohort 2: GS-1720 150 mg; Substudy 02: Cohort 3: GS-1720 30 mg; Substudy 02: Cohort 4: GS-1720 900 mg

Standard of Care (Substudy 02) DRUG

Antiretroviral therapy, administered orally Example INSTIs: DTG/ABC/3TC or DTG/3TC

Substudy 02: Cohort 1: GS-1720 450 mg; Substudy 02: Cohort 2: GS-1720 150 mg; Substudy 02: Cohort 3: GS-1720 30 mg; Substudy 02: Cohort 4: GS-1720 900 mg

GS-6212 DRUG

Administered orally

Substudy 03: Cohort 1: GS- 6212 100 mg

Standard of Care (Substudy 03) DRUG

Antiretroviral therapy, administered orally

Substudy 03: Cohort 1: GS- 6212 100 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (42)

Long Beach Education and Research Consultants,Substudy-03

Long Beach, California, 90813, United States

Location

Mills Clinical Research,Substudy-02

Los Angeles, California, 90069, United States

Location

Mills Clinical Research,Substudy-03

Los Angeles, California, 90069, United States

Location

Quest Clinical Research,Substudy-01

San Francisco, California, 94115, United States

Location

Quest Clinical Research,Substudy-02

San Francisco, California, 94115, United States

Location

Quest Clinical Research,Substudy-03

San Francisco, California, 94115, United States

Location

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

New Haven, Connecticut, 06510, United States

Location

Yale University,Substudy-02

New Haven, Connecticut, 06520, United States

Location

Washington Health Institute,Substudy-01

Washington D.C., District of Columbia, 20017, United States

Location

Washington Health Institute,Substudy-02

Washington D.C., District of Columbia, 20017, United States

Location

Washington Health Institute,Substudy-03

Washington D.C., District of Columbia, 20017, United States

Location

Midland Florida Clinical Research Center, LLC,Substudy-02

DeLand, Florida, 32720, United States

Location

Midland Florida Clinical Research, LLC,Substudy-03

DeLand, Florida, 32720, United States

Location

Midway Immunology and Research Center,Substudy-01

Ft. Pierce, Florida, 34982, United States

Location

Midway Immunology and Research Center,Substudy-02

Ft. Pierce, Florida, 34982, United States

Location

Midway Immunology and Research Center,Substudy-03

Ft. Pierce, Florida, 34982, United States

Location

Bliss Health,Substudy-02

Orlando, Florida, 32803, United States

Location

Bliss Health,Substudy-03

Orlando, Florida, 32803, United States

Location

Orlando Immunology Center,Substudy-01

Orlando, Florida, 32803, United States

Location

Orlando Immunology Center,Substudy-03

Orlando, Florida, 32803, United States

Location

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

West Palm Beach, Florida, 33407, United States

Location

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

West Palm Beach, Florida, 33407, United States

Location

Infectious Disease Specialists of Atlanta,Substudy-01

Decatur, Georgia, 30033, United States

Location

Indiana CTSI Clinical Research Center,Substudy-01

Indianapolis, Indiana, 46202, United States

Location

University of Cincinnati College of Medicine,Substudy-02

Cincinnati, Ohio, 45267, United States

Location

University of Cincinnati College of Medicine,Substudy-03

Cincinnati, Ohio, 45267, United States

Location

Central Texas Clinical Research,Substudy-01

Austin, Texas, 78705, United States

Location

Central Texas Clinical Research,Substudy-03

Austin, Texas, 78705, United States

Location

Prism Health North Texas,Substudy-02

Dallas, Texas, 75208, United States

Location

Prism Health North Texas,Substudy-03

Dallas, Texas, 75215, United States

Location

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

Dallas, Texas, 75246, United States

Location

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

Dallas, Texas, 75246, United States

Location

AXCES Research,Substudy-02

El Paso, Texas, 79902, United States

Location

AXES Research Group LLC,Substudy-03

El Paso, Texas, 79902, United States

Location

Therapeutic Concepts, PA,Substudy-02

Houston, Texas, 77004, United States

Location

Therapeutic Concepts, PA,Substudy-03

Houston, Texas, 77004, United States

Location

The Crofoot Research Center, Inc.,Substudy-01

Houston, Texas, 77098, United States

Location

MultiCare Rockwood Main Clinic- Research,Substudy-03

Spokane, Washington, 99202, United States

Location

Instituto Dominicano de Estudio Virologicos - IDEV,Substudy-02

Santo Domingo, 10103, Dominican Republic

Location

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

Bangkok, 10330, Thailand

Location

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

Bangkok, 10330, Thailand

Location

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

Khon Kaen, 40002, Thailand

Location

Related Publications (1)

• 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.

  BACKGROUND

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

bictegravir, emtricitabine, tenofovir alafenamide, drug combination; Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The Substudies were conducted in parallel. However, the cohorts within the Substudies received drug assignment sequentially.

Study Record Dates

• First Submitted: October 14, 2022
• First Posted: October 18, 2022
• Study Start: October 26, 2022
• Primary Completion: February 17, 2024
• Study Completion: March 18, 2024
• Last Updated: May 8, 2025
• Results First Posted: May 8, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

TH (3); DO (1); US (38)