Study of GS-3242 in Participants With HIV-1; Substudy-05

An Umbrella Phase 1b, Open-label, Multi-Cohort Study to Evaluate Safety, Pharmacokinetics, and Antiviral Activity of Novel Antiretrovirals in Participants With HIV-1 Substudy-05: GS-3242

This study is part of a master study. The goal of master protocol (GS-US-544-5905, NCT05585307) 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 GS-US-544-5905-05 is to learn more about the study drug GS-3242 in PWH.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: GS-3242; Drug: BVY; Drug: Standard of Care

Detailed Description

To refer master study protocol (GS-US-544-5905), refer to NCT05585307 on https://clinicaltrials.gov/

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 6170
    • ProcliniQ Investigación Clínica S.A. de C.V
• Thailand
  • Bangkok, Thailand, 10700
    • Faculty of Medicine Siriraj Hospital, Mahidol University
  • Bangkok, Thailand, 10400
    • Faculty of Medicine Ramathibodi Hospital, Mahidol University
  • Bangkok, Thailand, 10330
    • Institute of HIV Research and Innovation (IHRI)
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital, Faculty of Medicine, Khon Kaen University
  • Nonthaburi, Thailand, 11000
    • Bamrasnaradura Infectious Diseases Institute
  • Pathumwan, Thailand, 10330
    • The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT),Thai Red Cross AIDS and Infectious Disease Research Center
• United States
  • California
    • Bakersfield, California, United States, 93301
      • Franco Felizarta, MD
    • Los Angeles, California, United States, 90069
      • Mills Clinical Research
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group, Inc
    • San Francisco, California, United States, 94115
      • Quest Clinical Research
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20017
      • Washington Health Institute
  • Florida
    • DeLand, Florida, United States, 32720
      • Midland Florida Clinical Research Center, LLC
    • Fort Lauderdale, Florida, United States, 33308
      • Aids Healthcare Foundation - Northpoint
    • Ft. Pierce, Florida, United States, 34982
      • Midway Immunology & Research Center, LLC
    • Orlando, Florida, United States, 32803
      • Bliss Health
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center, PA
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute, P.A.
  • Georgia
    • Savannah, Georgia, United States, 31401
      • Chatham County Health Department
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • KC Care health Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati College of Medicine
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Dallas, Texas, United States, 75208
      • Prism Health North Texas
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Diseases Consultant's, P.A.
    • El Paso, Texas, United States, 79902
      • AXCES Research Group, LLC
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • AXCES Research Group, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key 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), injectable rilpivirine (RPV) or injectable Lenacapavir (LEN) 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-05:

• Willing to initiate BVY provided by the sponsor, or an alternative SOC ART regimen selected by the investigator on Day 11 or upon ET.
• Participants must also be willing to comply with meal requirements on dosing days.

Key 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:

  • 1. Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit, or
  • 2. 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, or injectable LEN, for treatment or prophylaxis (PrEP, PEP).

Substudy-05:

• Requirement for ongoing therapy with any prohibited medication.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cohort 1: Single Dose of GS-3242; Participants in cohort 1 will receive single dose of GS-3242 450 mg on Days 1 and 2 in the fasted condition. After assessments on Day 11 or upon early termination (ET), the participants initiate a regimen of bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy®) (BVY), 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. Following the completion of Cohort 1, additional cohorts may be opened for enrollment if further data are needed. Doses of GS-3242 will be based on safety and pharmacokinetic (PK) data from ongoing Phase 1a studies.

Drug: GS-3242; Administered orally; Drug: BVY; Administered orally; Other Names: Biktarvy®; Drug: Standard of Care; Antiretroviral therapy, administered orally Non-NNRTIs, examples: ABC/ DTG/3TC; DTG plus (TAF or TDF) plus (FTC or 3TC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma HIV-1 RNA (log10 Copies/mL) at Day 8 Relative to Historical Placebo Data		Baseline, Day 8
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)		First dose up to Day 39
Percentage of Participants With Graded Laboratory Abnormalities		First dose up to Day 39
Pharmacokinetic (PK) Parameter: Cmax of GS-3242	Cmax is defined as the maximum observed concentration of drug.	Day 1 Predose up to Day 11
PK Parameter: Ct of GS-3242	Ct is defined as the concentration at specified time "t".	Any day between Day 1 Predose up to Day 11
Percentage of Participants at Any Measurement Achieving HIV-1 RNA < 50 Copies/mL by Day 11 at Each Dose Level		Up to Day 11
Percentage of Participants With Emergence of Viral Resistance to the ARV Class of the Given Drug (GS-3242)		Up to Day 11
PK Parameter: AUC of GS-3242	AUC is defined as the area under the concentration versus time curve (AUC).	Day 1 Predose up to Day 11
Correlation Between Ct and/ or AUC versus the Change in Plasma HIV-1 RNA (Log10 Copies/mL) from Day 1 Through Day 11		Day 1 up to Day 11

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2025
• Primary Completion (Actual): March 3, 2026
• Study Completion (Actual): April 16, 2026

Study Registration Dates

• First Submitted: May 23, 2025
• First Submitted That Met QC Criteria: May 23, 2025
• First Posted (Actual): June 3, 2025

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care; bictegravir, emtricitabine, tenofovir alafenamide, drug combination
• Other Study ID Numbers: GS-US-544-5905-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No