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

Investigating Safety and Effects of Investigational Medications that Stop the Virus from Multiplying in HIV-1 Patients

S
Samir Gupta, MD

Primary Investigator

Enrolling By Invitation
18 years - 100 years
All
Phase 1/2
30 participants needed
2 Locations

Brief description of study

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.

THIS STUDY IS ENROLLING BY INVITATION ONLY

Detailed description of study

This is an open-label, Phase 1b, single or multiple dose, multicenter, umbrella study designed
to evaluate safety, PK, and antiviral activity of novel ARV agents given as monotherapy in
PWH who are either treatment-naive or treatment-experienced but naive to the study drug
class under investigation and have not received any ARVs within 12 weeks of screening,
including medications received for pre-exposure prophylaxis (PrEP) or postexposure
prophylaxis (PEP). Any current or prior receipt of long-acting parenteral ARVs such as
monoclonal antibodies (mAbs) targeting HIV-1, injectable cabotegravir, or injectable
rilpivirine is exclusionary.


This umbrella study will consist of a master protocol describing information relevant to all
substudies which will be associated with substudy protocols for each of the novel ARVs being
evaluated. This flexible clinical study design allows for opening new substudies as new agents
become available and closing substudies with study drugs that demonstrate minimal clinical
activity and/or unacceptable toxicity.


This umbrella study will begin with a substudy of GS-5894 (Substudy-01), and new substudies
may be added in the future. Substudies evaluating additional study drugs will be added in a
staggered manner when relevant nonclinical and/or clinical data become available.
After screening and meeting all eligibility criteria, study drug dosing will be initiated on Day 1
in the clinic for each participant. Participants will be required to return to the clinic for visits
on Days 2, 3, 4, 7, 8, 9, 10, and 11 (primary endpoint assessment). After assessments on
Day 11 or upon early termination, participants will initiate a standard-of-care (SOC)
antiretroviral therapy (ART) regimen. More details on eligible SOC ART regimens will be
provided in each substudy protocol. Participants will then be required to return to the clinic for
visits periodically over a specified duration as defined in each substudy protocol. The
follow-up duration during this period will be up to 5 half-lives since the last dose of the study
drug.
 

Each substudy may enroll approximately 5 cohorts of up to 8 participants per cohort.
Participants will be enrolled in Cohort 1 initially and then dosing in subsequent cohorts will
proceed after safety review team (SRT) review of emerging data. Additional optional SRT
reviews may also be conducted as applicable.

For each substudy, the doses and dosing regimen for study drug in each cohort will be selected
based on a review of available PK, cumulative safety and HIV-1 RNA data through the
primary endpoint (Day 11), and/or relevant and available safety and PK data from the ongoing
Phase 1a first-in-human (FIH) study of each study drug.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: HIV-1 Infection
  • Age: 18 years - 100 years
  • Gender: All

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.

Updated on 26 Aug 2025. Study ID: INFD-GILEAD-GS-US-544-5905-05, 27460

This study investigates the safety, pharmacokinetics, and antiviral activity of investigational antiretroviral agents in people living with HIV-1. The purpose is to understand how these agents affect the virus, which is responsible for HIV infection. Antiretrovirals are medications that stop the virus from multiplying, thereby managing the infection.

Participants will receive either a single or multiple doses of the investigational medication as monotherapy. The study will involve several visits to the clinic for assessments, including monitoring of safety and effectiveness of the treatment. Participants will then transition to a standard antiretroviral therapy after the initial study period.

  • Who can participate: Adults with HIV-1 who have a viral load between 5,000 and 400,000 copies/mL and a CD4 cell count over 200 cells/mm³ can participate. They must be treatment-naive or have not received antiretrovirals within 12 weeks of screening.
  • Study details: Participants will take the investigational medication and return for clinic visits for monitoring. After the study drug phase, they will switch to a standard antiretroviral therapy.
  • Study visits: The study requires 9 visits.
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Interested in the study?

This study is accepting only persons who receive care at a certain clinic or doctor or who are part of an invited group. Questions about this study can be directed to the study team listed in the description or contact your doctor to see if you are eligible.

Accepting Referrals by Invitation Only