Clinical trial NCT07001319: Study of GS-3242 in Participants With HIV-1
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: HIV-1-infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2025-06-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: To refer master study protocol (GS-US-544-5905), refer to NCT05585307 on www.clincialtrials.gov.

Eligibility 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.

Primary outcomes:
measure: Change From Baseline in Plasma Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) (log10 Copies/mL) at Day 11 Relative to Historical Placebo Data
timeFrame: Baseline, Day 11
Secondary outcomes:
measure: Change From Baseline in Plasma HIV-1 RNA (log10 Copies/mL) at Day 8 Relative to Historical Placebo Data
timeFrame: Baseline, Day 8
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: First dose up to Day 39
measure: Percentage of Participants With Graded Laboratory Abnormalities
timeFrame: First dose up to Day 39
measure: Pharmacokinetic (PK) Parameter: Cmax of GS-3242
timeFrame: Day 1 Predose up to Day 11
measure: PK Parameter: AUC of GS-3242
timeFrame: Day 1 Predose up to Day 11
measure: PK Parameter: Ct of GS-3242
timeFrame: Any day between Day 1 Predose up to Day 11
measure: Correlation Between Ct and/ or AUC versus the Reduction of Plasma HIV-1 RNA (Log10 Copies/mL) from Day 1 Through Day 11
timeFrame: Day 1 up to Day 11
measure: Percentage of Participants at Any Measurement Achieving HIV-1 RNA < 50 Copies/mL by Day 11 at Each Dose Level
timeFrame: Up to Day 11
measure: Percentage of Participants With Emergence of Viral Resistance to the ARV Class of the Given Drug (GS-3242)
timeFrame: Up to Day 11
Other outcomes:
Locations:
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: