HIV-1-infectionPhase 1NCT05585307
Study of Novel Antiretrovirals in Participants With HIV-1
A Phase 1 study testing Bavtavirine, B/F/TAF and GS-1720 in people with HIV-1-infection, run by Gilead Sciences at 42 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- Bavtavirine, B/F/TAF and GS-1720
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 42 sitesin 3 countries
- Study dates
- 26 Oct 2022to 18 Mar 2024
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
- 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 locations and contacts
42 sites in 3 countries.
42 sites in 3 countries
United States38 sites
Central Texas Clinical Research,Substudy-01
Austin, Texas, 78705
Central Texas Clinical Research,Substudy-03
Austin, Texas, 78705
University of Cincinnati College of Medicine,Substudy-02
Cincinnati, Ohio, 45267
University of Cincinnati College of Medicine,Substudy-03
Cincinnati, Ohio, 45267
Prism Health North Texas,Substudy-02
Dallas, Texas, 75208
Prism Health North Texas,Substudy-03
Dallas, Texas, 75215
North Texas Infectious Diseases Consultant, P.A.,Substudy-02
Dallas, Texas, 75246
North Texas Infectious Diseases Consultants, P.A.,Substudy-03
Dallas, Texas, 75246
Infectious Disease Specialists of Atlanta,Substudy-01
Decatur, Georgia, 30033
Midland Florida Clinical Research Center, LLC,Substudy-02
DeLand, Florida, 32720
Midland Florida Clinical Research, LLC,Substudy-03
DeLand, Florida, 32720
AXCES Research,Substudy-02
El Paso, Texas, 79902
AXES Research Group LLC,Substudy-03
El Paso, Texas, 79902
Midway Immunology and Research Center,Substudy-01
Ft. Pierce, Florida, 34982
Midway Immunology and Research Center,Substudy-02
Ft. Pierce, Florida, 34982
Midway Immunology and Research Center,Substudy-03
Ft. Pierce, Florida, 34982
Therapeutic Concepts, PA,Substudy-02
Houston, Texas, 77004
Therapeutic Concepts, PA,Substudy-03
Houston, Texas, 77004
The Crofoot Research Center, Inc.,Substudy-01
Houston, Texas, 77098
Indiana CTSI Clinical Research Center,Substudy-01
Indianapolis, Indiana, 46202
Long Beach Education and Research Consultants,Substudy-03
Long Beach, California, 90813
Mills Clinical Research,Substudy-02
Los Angeles, California, 90069
Mills Clinical Research,Substudy-03
Los Angeles, California, 90069
Yale University; School of Medicine; AIDS Program (Administrative & Study Supplies),Substudy-03
New Haven, Connecticut, 06510
Yale University,Substudy-02
New Haven, Connecticut, 06520
Bliss Health,Substudy-02
Orlando, Florida, 32803
Bliss Health,Substudy-03
Orlando, Florida, 32803
Orlando Immunology Center,Substudy-01
Orlando, Florida, 32803
Orlando Immunology Center,Substudy-03
Orlando, Florida, 32803
Quest Clinical Research,Substudy-01
San Francisco, California, 94115
Quest Clinical Research,Substudy-02
San Francisco, California, 94115
Quest Clinical Research,Substudy-03
San Francisco, California, 94115
MultiCare Rockwood Main Clinic- Research,Substudy-03
Spokane, Washington, 99202
Washington Health Institute,Substudy-01
Washington D.C., District of Columbia, 20017
Washington Health Institute,Substudy-02
Washington D.C., District of Columbia, 20017
Washington Health Institute,Substudy-03
Washington D.C., District of Columbia, 20017
Triple O Research Institute, P.A.,Substudy-01
West Palm Beach, Florida, 33407
Triple O Research Institute, P.A.,Substudy-03
West Palm Beach, Florida, 33407
Thailand3 sites
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT),Substudy-02
Bangkok, 10330
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT),Substudy-03
Bangkok, 10330
Faculty of Medicine, Srinagarind Hospital, Khon Kaen University,Substudy-03
Khon Kaen, 40002
Dominican Republic1 site
Instituto Dominicano de Estudio Virologicos - IDEV,Substudy-02
Santo Domingo, 10103
About this study
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
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.
Read the 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.
- Conditions
- HIV-1-infection
- Being tested
- Bavtavirine, B/F/TAF, Standard of Care (Substudy 01), GS-1720, Standard of Care (Substudy 02)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BavtavirineDrug
Also called GS-5894
Administered orally
B/F/TAFDrug
Also called Biktarvy®
Administered orally
Standard of Care (Substudy 01)Drug
Antiretroviral therapy, administered orally
Non-NNRTIs, examples: ABC/DTG/3TC; DTG plus (TAF or TDF) plus (FTC or 3TC)
GS-1720Drug
Administered orally
Standard of Care (Substudy 02)Drug
Antiretroviral therapy, administered orally
Example INSTIs: DTG/ABC/3TC or DTG/3TC
GS-6212Drug
Administered orally
Standard of Care (Substudy 03)Drug
Antiretroviral therapy, administered orally
| Study group | Role | What they receive |
|---|---|---|
| Substudy 01: Cohort 1: Bavtavirine 675 mg (High-Fat Meal) | Experimental | 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. Receives: Drug: Bavtavirine; Drug: B/F/TAF; Drug: Standard of Care (Substudy 01) |
| Substudy 01: Cohort 2: Bavtavirine 1200 mg (Low-Fat Meal) | Experimental | 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. Receives: Drug: Bavtavirine; Drug: B/F/TAF; Drug: Standard of Care (Substudy 01) |
| Substudy 01: Cohort 3: Bavtavirine 900 mg (High-Fat Meal) | Experimental | 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. Receives: Drug: Bavtavirine; Drug: B/F/TAF; Drug: Standard of Care (Substudy 01) |
| Substudy 02: Cohort 1: GS-1720 450 mg | Experimental | 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. Receives: Drug: B/F/TAF; Drug: GS-1720; Drug: Standard of Care (Substudy 02) |
| Substudy 02: Cohort 2: GS-1720 150 mg | Experimental | 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. Receives: Drug: B/F/TAF; Drug: GS-1720; Drug: Standard of Care (Substudy 02) |
| Substudy 02: Cohort 3: GS-1720 30 mg | Experimental | 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. Receives: Drug: B/F/TAF; Drug: GS-1720; Drug: Standard of Care (Substudy 02) |
| Substudy 02: Cohort 4: GS-1720 900 mg | Experimental | 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. Receives: Drug: B/F/TAF; Drug: GS-1720; Drug: Standard of Care (Substudy 02) |
| Substudy 03: Cohort 1: GS- 6212 100 mg | Experimental | 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. Receives: Drug: B/F/TAF; Drug: GS-6212; Drug: Standard of Care (Substudy 03) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline, Day 11
Secondary outcomes (20)
Substudies 01, 02 and 03: Change From Baseline in Plasma HIV-1 RNA (log10 Copies/mL) at Day 8 Relative to Historical Placebo Data
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1 up to Day 11
Substudy 01: PK Parameter: Plasma Concentration of Bavtavirine
Measured: Days 8 and 11
Substudy 02: PK Parameter: Cmax of GS-1720
Cmax was defined as the maximum observed concentration of drug.
Measured: 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.
Measured: Day 1 up to Day 11
Substudy 02: PK Parameter: Plasma Concentration of GS-1720
Measured: Days 8 and 11
Substudy 03: PK Parameter: Cmax of GS-6212
Cmax was defined as the maximum observed concentration of drug.
Measured: 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.
Measured: 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.
Measured: Day 10 (Parameter estimated based on observed data from 0 to 8 hours postdose)
Substudy 03: PK Parameter: Plasma Concentration of GS-6212
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 11
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2022
- Study start26 Oct 2022
- Primary completion17 Feb 2024
- Study completion18 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- The Substudies were conducted in parallel. However, the cohorts within the Substudies received drug assignment sequentially.
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05585307
- Sponsor's protocol ID
- GS-US-544-5905
- Status last verified
- Apr 2025
- First submitted
- 14 Oct 2022
- Last updated
- 8 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.