Phase 1
N=49
Study of Novel Antiretrovirals in Participants With HIV-1
HIV-1-infection
Bottom Line
View on ClinicalTrials.gov: NCT05585307 ↗Enrolled (actual)
49
Serious AEs
4.1%
Results posted
May 2025
Primary outcome: Primary: 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 — 4.68; 4.68; 4.27; 5.16 log10 copies/mL — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Bavtavirine (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)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Gilead Sciences
- Primary completion
- Feb 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
4.68; 4.68; 4.27; 5.16; 4.72; 4.52 | <0.0001 sig |
| SECONDARY Substudies 01, 02 and 03: Change From Baseline in Plasma HIV-1 RNA (log10 Copies/mL) at Day 8 Relative to Historical Placebo Data |
4.68; 4.68; 4.27; 5.16; 4.72; 4.52 | <0.0001 sig |
| SECONDARY Substudies 01, 02 and 03: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) |
50.0; 16.7; 100; 42.9; 85.7; 85.7 | — |
| SECONDARY Substudies 01, 02 and 03: Percentage of Participants With Graded Laboratory Abnormalities |
100; 100; 100; 100; 100; 100 | — |
| SECONDARY Substudy 01: Pharmacokinetic (PK) Parameter: Cmax of Bavtavirine |
685; 700; 565; 1160 | — |
| SECONDARY Substudy 01: PK Parameter: AUC of Bavtavirine |
33,300; 24,300; 71,400; 38,800; 28,300; 89,100 | — |
| SECONDARY Substudy 01: PK Parameter: Plasma Concentration of Bavtavirine |
94.5; 64.8; 250; 61.2; 44.6; 202 | — |
| SECONDARY Substudy 02: PK Parameter: Cmax of GS-1720 |
17.2; 9.77; 3.00; 33.7; 30.8; 15.6 | — |
| SECONDARY Substudy 02: PK Parameter: AUC of GS-1720 |
2790; 1670; 503; 4960; 3540; 2160 | — |
| SECONDARY Substudy 02: PK Parameter: Plasma Concentration of GS-1720 |
12.2; 7.44; 2.59; 22.7; 8.78; 5.87 | — |
| SECONDARY Substudy 03: PK Parameter: Cmax of GS-6212 |
1590; 1550 | — |
| SECONDARY Substudy 03: PK Parameter: AUC0-8h of GS-6212 |
5030; 5700 | — |
| SECONDARY Substudy 03: PK Parameter: AUCtau of GS-6212 |
6450 | — |
| SECONDARY Substudy 03: PK Parameter: Plasma Concentration of GS-6212 |
221; 260 | — |
| SECONDARY Substudy 03: PK Parameter: Ctrough of GS-6212 (Day 10) |
140 | — |
| SECONDARY Substudy 03: PK Parameter: Cavg of GS-6212 (Day 10) |
538 | — |
| SECONDARY 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 |
0; 0; 0; 0; 0; 28.6 | — |
| SECONDARY Substudies 01, 02 and 03: Percentage of Participants With Emergence of Viral Resistance to the ARV Class of the Given Drug |
33.0; 16.6; 0; 0; 0; 0 | — |
| SECONDARY Substudy 01: Maximum Inhibitory Quotient (IQ) of Bavtavirine by Mean Plasma Concentration (Ct) up to Day 11 |
5; 5; 5 | — |
| SECONDARY Substudy 02: Inhibitory Quotient (IQ) of GS-1720 by Mean Plasma Concentration (Ct) at Day 11 |
4.5; 3; 0.8; 9.5 | — |
| SECONDARY Substudy 03: Inhibitory Quotient (IQ) of GS-6212 by Ctrough at Day 11 |
6.5 | — |
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.
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.
Eligibility 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 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.
Data sourced from ClinicalTrials.gov (NCT05585307). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.