Purpose

Master protocol: The goal of this master clinical trial study 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-01 (GS-US-544-5905-01) will evaluate GS-5894 in PWH. Substudy-02 (GS-US-544-5905-02) will evaluate GS-1720 in PWH. Substudy-03 (GS-US-544-5905-03) will evaluate GS-6212 in PWH.

Condition

Eligibility

Eligible Ages
Between 18 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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), or injectable rilpivirine (RPV) 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-01, Substudy-02, and Substudy-03: - Participants in substudy-01 should be willing to initiate a non-NNRTI based SOC ART on Day 11. - Participants in substudy-02 and Substudy-03 should be willing to initiate any SOC ART on Day 11. - Willing and able to comply with meal requirements on dosing days.

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: - 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. - 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, for treatment or prophylaxis (PrEP, PEP). Substudy-01, Substudy-02, Substudy-03: - Requirement for ongoing therapy with any prohibited medications listed in protocol. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Substudy-01: GS-5894
Participants will receive GS-5894. After assessments on Day 11 or upon early termination (ET), participants will initiate a regimen of Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY)), or other non-nonnucleoside reverse transcriptase inhibitor (NNRTI) based standard of care (SOC) antiretroviral therapy (ART) regimen up to Day 39. Non-NNRTI SOC ART regimen may include: abacavir (ABC)/dolutegravir (DTG)/lamivudine (3TC), (ABC/DTG/3TC) DTG plus (tenofovir alafenamide fumarate (TAF) or tenofovir disoproxil fumarate (TDF) plus (emtricitabine (FTC) or 3TC) Approximately 5 cohorts may enroll. 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.
  • Drug: GS-5894
    Administered orally
  • Drug: B/F/TAF
    Administered orally
    Other names:
    • Biktarvy®
  • Drug: Standard of Care (Substudy 01)
    Antiretroviral therapy, administered orally Non-NNRTIs, examples: ABC/DTG/3TC; DTG plus (TAF or TDF) plus (FTC or 3TC)
Experimental
Substudy-02: GS-1720
Participants will receive GS-1720. After assessments on Day 11 or upon ET, participants will initiate a regimen of Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY)), or an alternative SOC ART regimen up to Day 60. SOC ART regimen, example INSTIs: DTG/ABC/3TC or DTG/3TC Approximately 5 cohorts may enroll. 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.
  • Drug: B/F/TAF
    Administered orally
    Other names:
    • Biktarvy®
  • Drug: GS-1720
    Administered orally
  • Drug: Standard of Care (Substudy 02)
    Antiretroviral therapy, administered orally Example INSTIs: DTG/ABC/3TC or DTG/3TC
Experimental
Substudy-03: GS-6212
Participants will receive GS-6212. After assessment on Day 11 or upon ET, participants will initiate a regimen of Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY)), or an alternative SOC ART regimen up to Day 25. Approximately 5 cohorts may enroll. 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.
  • Drug: B/F/TAF
    Administered orally
    Other names:
    • Biktarvy®
  • Drug: GS-6212
    Administered orally
  • Drug: Standard of Care (Substudy 03)
    Antiretroviral therapy, administered orally

Recruiting Locations

More Details

Status
Recruiting
Sponsor
Gilead Sciences

Study Contact

Gilead Clinical Study Information Center
1-833-445-3230 (GILEAD-0)
GileadClinicalTrials@gilead.com

Detailed Description

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. - Substudy-01 enrollment closed, actual enrollment is 13. - Substudy-02 planned enrollment is 30. - Substudy-03 planned enrollment is 30.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.