GS-1720 + GS-4182 for HIV

Recruiting at 47 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Gilead Sciences

Must not be taking: Long-acting ARVs

Disqualifiers: Hepatitis B, Hepatitis C, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The goal of this clinical study is to learn more about the experimental drugs GS-1720 (an oral, long-acting integrase strand transfer inhibitor (INSTI)) and GS-4182 (a prodrug of Lenacapavir (LEN)); to compare the combination of GS-1720 and GS-4182 with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (Biktarvy), to see if the combination of GS-1720 and GS-4182 is safe and if it works for treating human immunodeficiency virus type 1 (HIV-1) infection in treatment-naive people with HIV-1 (PWH). This study has two phases: Phase 2 and Phase 3. The primary objectives of this study are: Phase 2: To evaluate the efficacy of oral weekly GS-1720 coadministered with GS-4182 versus continuing Biktarvy (BVY) in treatment-naive PWH at Week 24. Phase 3: To evaluate the efficacy of oral weekly GS-1720/GS-4182 fixed-dose combination (FDC) tablet regimen versus continuing BVY in treatment-naive PWH at Week 48.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should be treatment-naive, meaning they haven't used antiretroviral treatments before, except for certain short-term preventive treatments. It's best to discuss your current medications with the trial team.

What makes the drug GS-1720 + GS-4182 unique for treating HIV?

The drug GS-1720 + GS-4182 is unique because it combines two components that may target different aspects of the HIV virus, potentially offering a novel approach compared to existing treatments. However, specific details about its mechanism or how it differs from other treatments are not provided in the available research. ^{1 2 3 4 5}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for people with HIV-1 who haven't been treated before. They must have an HIV-1 RNA count of at least 500 copies/mL and can have used pre-exposure or postexposure prophylaxis up to a month before screening.

Inclusion Criteria

Key

My HIV-1 RNA level is 500 copies/mL or more.

I haven't taken HIV drugs, except for short-term prevention.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 2 Treatment

Participants receive either GS-1720 and GS-4182 or B/F/TAF for at least 48 weeks

48 weeks

Phase 3 Treatment

Participants receive either GS-1720/GS-4182 FDC or B/F/TAF for at least 96 weeks

96 weeks

Extension Phase

Participants may opt into continuation of GS-1720/GS-4182 FDC treatment until the product becomes available or the study is discontinued

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• GS-1720 (Integrase Strand Transfer Inhibitor)
• GS-4182 (Prodrug of Lenacapavir)

Trial Overview The study tests GS-1720, an experimental oral drug, and GS-4182, its prodrug form, against Biktarvy (B/F/TAF), the current standard treatment. It's in two phases: Phase 2 checks efficacy at Week 24; Phase 3 compares a fixed-dose combo tablet regimen to Biktarvy at Week 48.

Participant Groups

Group I: Phase 3: GS-1720/GS-4182 FDC + Placebo to Match (PTM) B/F/TAF (Treatment Group 1) Experimental Treatment 2 Interventions

Participants will receive a 1-day loading dose of GS-1720/GS-4182 FDC on Day 1. Thereafter, participants will receive GS-1720/GS-4182 FDC tablets weekly + PTM B/F/TAF once daily. Participants will receive treatment for at least 96 weeks.

Group II: Phase 3 Extension Phase: GS-1720/GS-4182 Fixed-dose Combination (FDC) Experimental Treatment 1 Intervention

After the end of blinded treatment, Phase 3 participants will be given the option to participate in the Extension Phase. Phase 3 Treatment Group 1 will continue to receive GS-1720/GS-4182 FDC weekly while PTM B/F/TAF will be discontinued. Phase 3 Treatment Group 2 will switch to receive GS-1720/GS-4182 FDC tablets weekly. Participants in Treatment Group 2 will also receive a 1-day loading dose of GS-1720/GS-4182 FDC on Extension Phase Day 1. Participants who choose to enter the Phase 3 Extension Phase will receive GS-1720/GS-4182 FDC tablets until the product becomes available or until Gilead Sciences elects to discontinue the study, whichever occurs first.

Group III: Phase 2: GS-1720 + GS-4182 (Treatment Group 1) Experimental Treatment 2 Interventions

Participants will receive a 1-day loading dose of GS-1720 (1300 mg) and GS-4182 (600 mg) on Day 1.Thereafter, participants will take weekly doses of single agent GS-1720 (650 mg) and GS-4182 (300 mg) coadministered for at least 48 weeks.

Group IV: Phase 2 Extension Phase: GS-1720/GS-4182 Fixed-dose Combination (FDC) Experimental Treatment 1 Intervention

At the end of the randomized treatment, Phase 2 participants will be given the option to participate in the Extension Phase. Phase 2 Treatment Group 1 will switch to GS-1720/GS-4182 FDC (650/300 mg) weekly. Phase 2 Treatment Group 2 will receive a loading dose of GS-1720/GS-4182 FDC (1300 mg/600 mg) on Extension Phase Day 1, then GS-1720/GS-4182 FDC (650/300 mg) weekly. Participants who choose to enter the Extension Phase will receive GS-1720/GS-4182 FDC tablets until the product becomes available or until Gilead Sciences elects to discontinue the study, whichever occurs first.

Group V: Phase 2: B/F/TAF (Treatment Group 2) Active Control 1 Intervention

Participants will receive B/F/TAF (50/200/25 mg) daily for at least 48 weeks.

Group VI: Phase 3: B/F/TAF + PTM GS-1720/GS-4182 FDC (Treatment Group 2) Active Control 2 Interventions

Participants will receive oral B/F/TAF daily along with PTM GS-1720/GS-4182 FDC weekly for at least 96 weeks. Additionally, participants will receive a 1-day loading dose of PTM GS-1720/GS-4182 on Day 1.

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Findings from Research

The study identified the first intersubtype B/G recombinant strain of HIV-1 in Germany, which has significant implications for diagnosis and treatment due to its genetic diversity.

This strain was undetectable in one viral load assay and underquantitated in another, highlighting how genetic variations can affect the reliability of HIV detection and quantification methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The first B/G intersubtype recombinant form of human immunodeficiency virus type 1 (HIV-1) identified in Germany was undetected or underquantitated by some commercial viral load assays. von Truchsess, I., Harris, B., Schätzl, HM., et al.[2008]

The new integrase inhibitor S/GSK1349572 shows strong efficacy against HIV-2, with a median effective concentration (EC₅₀) of 0.8 nM, comparable to HIV-1 strains, indicating its potential as a treatment option.

However, HIV-2 mutants from patients previously treated with raltegravir exhibited significantly higher EC₅₀ values, suggesting that these mutations can reduce the effectiveness of S/GSK1349572, highlighting the need for careful monitoring of resistance in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-vitro phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitor S/GSK1349572. Charpentier, C., Larrouy, L., Collin, G., et al.[2022]

GSK3532795, a second-generation maturation inhibitor for HIV-1, showed specific resistance development linked to mutations near the capsid/spacer peptide 1 junction, indicating a targeted mechanism of action.

In a Phase 2a study involving HIV-1 infected participants, certain mutations associated with reduced susceptibility to GSK3532795 were observed, suggesting that resistance can develop during treatment and may impact the drug's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. Dicker, I., Zhang, S., Ray, N., et al.[2020]

BMS-663068, an oral prodrug for HIV treatment, showed promising efficacy with 80% of patients on the 400 mg twice daily dose achieving an HIV-1 RNA viral load of less than 50 copies per mL at week 24, comparable to the 75% response rate in the ritonavir-boosted atazanavir group.

The safety profile of BMS-663068 was favorable, with no serious adverse events linked to the drug and a lower incidence of grade 2-4 adverse events compared to ritonavir-boosted atazanavir, suggesting it is a viable option for treatment-experienced HIV-1 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in treatment-experienced individuals: 24 week results of AI438011, a phase 2b, randomised controlled trial. Lalezari, JP., Latiff, GH., Brinson, C., et al.[2019]

The HIV subtype B' variant, characterized by the amino acid sequence GWG, is associated with slower disease progression and higher CD4 counts in mono-infected patients, suggesting a potential better prognosis.

In coinfected patients with HIV and hepatitis C, the GWG variant did not show the same protective effects, indicating that its benefits may be lost in the presence of co-infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of the HIV GWG variant in the HIV infection progression in mono and HCV coinfected patients. Hebeler-Barbosa, F., Massolini, VM., Watanabe, T., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

The first B/G intersubtype recombinant form of human immunodeficiency virus type 1 (HIV-1) identified in Germany was undetected or underquantitated by some commercial viral load assays. [2008]

2. England pubmed.ncbi.nlm.nih.gov

In-vitro phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitor S/GSK1349572. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in treatment-experienced individuals: 24 week results of AI438011, a phase 2b, randomised controlled trial. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Influence of the HIV GWG variant in the HIV infection progression in mono and HCV coinfected patients. [2021]