Study of Novel Antiretrovirals in Participants With HIV-1

An Umbrella Phase 1b, Open-label, Multi-Cohort Study to Evaluate Safety, Pharmacokinetics, and Antiviral Activity of Novel Antiretrovirals in Participants With HIV-1

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.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: B/F/TAF; Drug: Standard of Care (Substudy 01); Drug: GS-1720; Drug: Standard of Care (Substudy 02); Drug: GS-6212; Drug: Standard of Care (Substudy 03); Drug: Bavtavirine

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• Dominican Republic
  • Santo Domingo, Dominican Republic, 10103
    • Instituto Dominicano de Estudio Virologicos - IDEV,Substudy-02
• Thailand
  • Bangkok, Thailand, 10330
    • The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT),Substudy-02
  • Bangkok, Thailand, 10330
    • The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT),Substudy-03
  • Khon Kaen, Thailand, 40002
    • Faculty of Medicine, Srinagarind Hospital, Khon Kaen University,Substudy-03
• United States
  • California
    • Long Beach, California, United States, 90813
      • Long Beach Education and Research Consultants,Substudy-03
    • Los Angeles, California, United States, 90069
      • Mills Clinical Research,Substudy-02
    • Los Angeles, California, United States, 90069
      • Mills Clinical Research,Substudy-03
    • San Francisco, California, United States, 94115
      • Quest Clinical Research,Substudy-01
    • San Francisco, California, United States, 94115
      • Quest Clinical Research,Substudy-02
    • San Francisco, California, United States, 94115
      • Quest Clinical Research,Substudy-03
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University; School of Medicine; AIDS Program (Administrative & Study Supplies),Substudy-03
    • New Haven, Connecticut, United States, 06520
      • Yale University,Substudy-02
  • District of Columbia
    • Washington, District of Columbia, United States, 20017
      • Washington Health Institute,Substudy-01
    • Washington, District of Columbia, United States, 20017
      • Washington Health Institute,Substudy-02
    • Washington, District of Columbia, United States, 20017
      • Washington Health Institute,Substudy-03
  • Florida
    • DeLand, Florida, United States, 32720
      • Midland Florida Clinical Research Center, LLC,Substudy-02
    • DeLand, Florida, United States, 32720
      • Midland Florida Clinical Research, LLC,Substudy-03
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center,Substudy-01
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center,Substudy-02
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center,Substudy-03
    • Orlando, Florida, United States, 32803
      • Bliss Health,Substudy-02
    • Orlando, Florida, United States, 32803
      • Bliss Health,Substudy-03
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center,Substudy-01
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center,Substudy-03
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute, P.A.,Substudy-01
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute, P.A.,Substudy-03
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta,Substudy-01
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana CTSI Clinical Research Center,Substudy-01
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati College of Medicine,Substudy-02
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati College of Medicine,Substudy-03
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research,Substudy-01
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research,Substudy-03
    • Dallas, Texas, United States, 75208
      • Prism Health North Texas,Substudy-02
    • Dallas, Texas, United States, 75215
      • Prism Health North Texas,Substudy-03
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Diseases Consultant, P.A.,Substudy-02
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Diseases Consultants, P.A.,Substudy-03
    • El Paso, Texas, United States, 79902
      • AXCES Research,Substudy-02
    • El Paso, Texas, United States, 79902
      • AXES Research Group LLC,Substudy-03
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, PA,Substudy-02
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, PA,Substudy-03
    • Houston, Texas, United States, 77098
      • The Crofoot Research Center, Inc.,Substudy-01
  • Washington
    • Spokane, Washington, United States, 99202
      • MultiCare Rockwood Main Clinic- Research,Substudy-03

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Substudy 01: Cohort 1: Bavtavirine 675 mg (High-Fat Meal); 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.	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); Drug: Bavtavirine; Administered orally; Other Names: GS-5894
Experimental: Substudy 01: Cohort 2: Bavtavirine 1200 mg (Low-Fat Meal); 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.	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); Drug: Bavtavirine; Administered orally; Other Names: GS-5894
Experimental: Substudy 01: Cohort 3: Bavtavirine 900 mg (High-Fat Meal); 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.	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); Drug: Bavtavirine; Administered orally; Other Names: GS-5894
Experimental: Substudy 02: Cohort 1: GS-1720 450 mg; 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.	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 02: Cohort 2: GS-1720 150 mg; 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.	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 02: Cohort 3: GS-1720 30 mg; 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.	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 02: Cohort 4: GS-1720 900 mg; 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.	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: Cohort 1: GS- 6212 100 mg; 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.	Drug: B/F/TAF; Administered orally; Other Names: Biktarvy®; Drug: GS-6212; Administered orally; Drug: Standard of Care (Substudy 03); Antiretroviral therapy, administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Substudies 01, 02 and 03: 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

Outcome Measure	Measure Description	Time Frame
Substudies 01, 02 and 03: Change From Baseline in Plasma HIV-1 RNA (log10 Copies/mL) at Day 8 Relative to Historical Placebo Data		Baseline, Day 8
Substudies 01, 02 and 03: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as any AEs with an onset date on or after the study drug start date. Percentages were rounded-off.	First dose up to last dose (Substudy 01: Up to Day 39; Substudy 02: Up to Day 60; Substudy 03: Up to Day 25)
Substudies 01, 02 and 03: Percentage of Participants With Graded Laboratory Abnormalities	Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any time postbaseline. Laboratory abnormalities were graded using Division of AIDS (DAIDS) scale with grade 0 to 4 where 0 = no grade; 1 = mild, 2 = moderate, 3 = severe; 4 = potentially life-threatening. Participants with at least a 1 grade increased from baseline for an individual laboratory test where the maximum post baseline laboratory abnormality was 1) grade 1 or higher and 2) grade 3 or higher were reported. The maximum postbaseline toxicity grade across all tests for an individual participant was used in analysis. Percentages were rounded-off.	First dose up to last dose (Substudy 01: Up to Day 39; Substudy 02: Up to Day 60; Substudy 03: Up to Day 25)
Substudy 01: Pharmacokinetic (PK) Parameter: Cmax of Bavtavirine	Cmax was defined as the maximum observed concentration of drug.	Cohorts 1, 2 and 3 (Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, and 12 hours postdose); Cohort 3: Day 2: Predose, 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Substudy 01: PK Parameter: AUC of Bavtavirine	AUC was defined as the area under the concentration versus time curve.	Day 1 up to Day 11
Substudy 01: PK Parameter: Plasma Concentration of Bavtavirine		Days 8 and 11
Substudy 02: PK Parameter: Cmax of GS-1720	Cmax was defined as the maximum observed concentration of drug.	Days 1 and 2: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and (optional) 12 hours postdose
Substudy 02: PK Parameter: AUC of GS-1720	AUC was defined as the area under the concentration versus time curve.	Day 1 up to Day 11
Substudy 02: PK Parameter: Plasma Concentration of GS-1720		Days 8 and 11
Substudy 03: PK Parameter: Cmax of GS-6212	Cmax was defined as the maximum observed concentration of drug.	Days 1 and 10 (Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8 and (optional) 12 hours postdose)
Substudy 03: PK Parameter: AUC0-8h of GS-6212	AUC0-8h was defined as the area under the concentration versus time curve spanning from 0 to 8 hours post dose.	Days 1 and 10 (Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8 and (optional) 12 hours postdose)
Substudy 03: PK Parameter: AUCtau of GS-6212	AUCtau was defined as the area under the curve from time zero to end of dosing interval.	Day 10 (Parameter estimated based on observed data from 0 to 8 hours postdose)
Substudy 03: PK Parameter: Plasma Concentration of GS-6212		Days 1 and 10: 8 hours postdose
Substudy 03: PK Parameter: Ctrough of GS-6212 (Day 10)	Ctrough was defined as concentration at the end of the dosing interval.	Day 10 (Parameter estimated based on observed data from 0 to 8 hours postdose)
Substudy 03: PK Parameter: Cavg of GS-6212 (Day 10)	Cavg was defined as average plasma concentration during dose administration.	Day 10 (predose to 8 hours postdose)
Substudies 01, 02 and 03: Percentage of Participants at Any Measurement Achieving HIV-1 RNA < 50 Copies/mL by Day 11 at Each Dose Level	Percentages were rounded-off.	Up to Day 11
Substudies 01, 02 and 03: Percentage of Participants With Emergence of Viral Resistance to the ARV Class of the Given Drug	The antiretroviral (ARV) class of given drugs would be BVY or NNRTIs (Substudy 01) or INSTIs (Substudy 02) or INSTIs (Substudy 03). Percentages were rounded-off.	Up to Day 11
Substudy 01: Maximum Inhibitory Quotient (IQ) of Bavtavirine by Mean Plasma Concentration (Ct) up to Day 11	Inhibitory quotient was calculated as the ratio of bavtavirine in vivo exposure to in vitro plasma concentration. IQ is defined as paEC95. paEC95 = protein-adjusted effective concentration to achieve 95% effective inhibition. The IQ ≥ 2 indicated higher reduction in viral load with less rebound.	Up to Day 11
Substudy 02: Inhibitory Quotient (IQ) of GS-1720 by Mean Plasma Concentration (Ct) at Day 11	Inhibitory quotient was calculated as the ratio of GS-1720 in vivo exposure to in vitro plasma concentration. IQ is defined as paEC95. paEC95 = protein-adjusted effective concentration to achieve 95% effective inhibition. The IQ ≥ 2 indicated higher reduction in viral load with less rebound.	Day 11
Substudy 03: Inhibitory Quotient (IQ) of GS-6212 by Ctrough at Day 11	Ctrough is the plasma concentration of the drug just before the next dose. Inhibitory quotient was calculated as the ratio of GS-1720 in vivo exposure to in vitro Ctrough. IQ is defined as paEC95. paEC95 = protein-adjusted effective concentration to achieve 95% effective inhibition. The IQ ≥ 2 indicated higher reduction in viral load with less rebound.	Day 11

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General Publications

• Carl J. Fichtenbaum, Mezgebe Berhe, Jose Bordon, et al, Antiviral Activity, Safety, and Pharmacokinetics of GS-1720: A Novel Weekly Oral INSTI. Conference on Retroviruses and Opportunistic Infections, 2024, 3-6 March.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2022
• Primary Completion (Actual): February 17, 2024
• Study Completion (Actual): March 18, 2024

Study Registration Dates

• First Submitted: October 14, 2022
• First Submitted That Met QC Criteria: October 14, 2022
• First Posted (Actual): October 18, 2022

Study Record Updates

• Last Update Posted (Actual): May 8, 2025
• Last Update Submitted That Met QC Criteria: April 18, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: GS-US-544-5905

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No