Study of GS-3242 in Participants With HIV-1
- Conditions
- HIV-1-infection
- Interventions
- Registration Number
- NCT07001319
- Lead Sponsor
- Gilead Sciences
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 30
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
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.
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Hepatitis C virus (HCV) antibody positive and detectable HCV RNA.
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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.
-
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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.
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Positive serum pregnancy test at screening or a positive pregnancy test prior to Day 1.
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Individuals with plan to breastfeed during the study period including the protocol-defined follow-up period.
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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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1: Single Dose of GS-3242 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. Cohort 1: Single Dose of GS-3242 BVY 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. Cohort 1: Single Dose of GS-3242 Standard of Care 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 Day 1 Predose up to Day 11 Cmax is defined as the maximum observed concentration of drug.
PK Parameter: AUC of GS-3242 Day 1 Predose up to Day 11 AUC is defined as the area under the concentration versus time curve.
PK Parameter: Ct of GS-3242 Any day between Day 1 Predose up to Day 11 Ct is defined as the concentration at specified time "t".
Correlation Between Ct and/ or AUC versus the Reduction of Plasma HIV-1 RNA (Log10 Copies/mL) from Day 1 Through Day 11 Day 1 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