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

Gilead Sciences

Status and phase: Enrolling; Phase 1

Conditions: HIV-1-infection

Treatments: Drug: Standard of Care; Drug: GS-3242; Drug: BVY

Study type: Interventional

Funder types: Industry

Identifiers

NCT07001319

GS-US-544-5905-05

Details and patient eligibility

About

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.

Full description

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

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Cohort 1: Single Dose of GS-3242

Experimental group

Description:

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.

Treatment:

Drug: BVY

Drug: Standard of Care

Drug: GS-3242