Study of Novel Antiretrovirals in Participants With HIV-1

Gilead Sciences

Status and phase

Completed

Phase 1

Conditions

HIV-1-infection

Treatments

Drug: Bavtavirine

Drug: Standard of Care (Substudy 01)

Drug: Standard of Care (Substudy 03)

Drug: Standard of Care (Substudy 02)

Drug: GS-6212

Drug: B/F/TAF

Drug: GS-1720

Study type

Interventional

Funder types

Industry

Identifiers

NCT05585307

GS-US-544-5905

Details and patient eligibility

About

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 bavtavirine 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.

Full description

This umbrella study will begin with a substudy of bavtavirine (Substudy-01), and later substudies GS-1720 (Substudy-02) and GS-6212 (Substudy-03) will be added. 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 enrollment closed, actual enrollment is 28.
Substudy-03 enrollment closed, actual enrollment is 8.

Enrollment

49 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), 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.

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:
- 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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

49 participants in 8 patient groups

Substudy 01: Cohort 1: Bavtavirine 675 mg (High-Fat Meal)

Experimental group

Description:

Participants receive a single dose of bavtavirine 675 mg tablet with a high-fat meal on Day 1. After assessments on Day 11 or upon early termination (ET), the participants initiate a regimen of B/F/TAF, 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.

Treatment:

Drug: B/F/TAF

Drug: Standard of Care (Substudy 01)

Drug: Bavtavirine

Substudy 01: Cohort 2: Bavtavirine 1200 mg (Low-Fat Meal)

Experimental group

Description:

Participants receive a single dose of bavtavirine 1200 mg tablet with a low-fat meal on Day 1. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 39.

Treatment:

Drug: B/F/TAF

Drug: Standard of Care (Substudy 01)

Drug: Bavtavirine

Substudy 01: Cohort 3: Bavtavirine 900 mg (High-Fat Meal)

Experimental group

Description:

Participants receive bavtavirine 900 mg tablet with a high-fat meal on Days 1 and 2. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 39.

Treatment:

Drug: B/F/TAF

Drug: Standard of Care (Substudy 01)

Drug: Bavtavirine

Substudy 02: Cohort 1: GS-1720 450 mg

Experimental group

Description:

Participants receive a single dose of GS-1720 450 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.

Treatment:

Drug: GS-1720

Drug: B/F/TAF

Drug: Standard of Care (Substudy 02)

Substudy 02: Cohort 2: GS-1720 150 mg

Experimental group

Description:

Participants receive a single dose of GS-1720 150 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.

Treatment:

Drug: GS-1720

Drug: B/F/TAF

Drug: Standard of Care (Substudy 02)

Substudy 02: Cohort 3: GS-1720 30 mg

Experimental group

Description:

Participants receive a single dose of GS-1720 30 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.

Treatment:

Drug: GS-1720

Drug: B/F/TAF

Drug: Standard of Care (Substudy 02)

Substudy 02: Cohort 4: GS-1720 900 mg

Experimental group

Description:

Participants receive a single dose of GS-1720 900 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.

Treatment:

Drug: GS-1720

Drug: B/F/TAF

Drug: Standard of Care (Substudy 02)

Substudy 03: Cohort 1: GS- 6212 100 mg

Experimental group

Description:

Participants receive GS-6212 100 mg tablet twice daily on Days 1 through 10. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 25.

Treatment:

Drug: B/F/TAF

Drug: Standard of Care (Substudy 03)

Drug: GS-6212

Trial documents