Study of Oral Weekly GS-1720 and GS-4182 Versus Biktarvy in People With HIV-1 Who Are Virologically Suppressed

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gilead Sciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Decision date (initial)

2025-02-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Gilead Sciences, Inc.

External identifiers

EU CT number

2024-511054-50-00

ClinicalTrials.gov

NCT06544733

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Pharmacogenomic, Therapy, Safety, Pharmacokinetic

Phase 2:
To evaluate the efficacy of switching to oral weekly GS-1720 in combination with GS-4182 versus continuing bictegravir/emtricitabine/tenofovir alafenamide (BVY; coformulated, Biktarvy®) in virologically suppressed PWH at Week 24
Phase 3:
To evaluate the efficacy of switching to oral weekly GS-1720/GS-4182 fixed-dose combination (FDC) tablet regimen versus continuing BVY in virologically suppressed PWH at Week 48

Secondary objectives 5

1. Phase 2: To evaluate the efficacy of switching to oral weekly GS-1720 in combination with GS-4182 versus continuing BVY in virologically suppressed PWH at Weeks 12, 24, and 48
2. Phase 2:To evaluate the safety and tolerability of oral weekly GS-1720 in combination with GS-4182 at Weeks 12, 24, and 48
3. Phase 2:To evaluate the PK of oral weekly GS-1720 in combination with GS-4182
4. Phase 3: To evaluate the efficacy of switching to oral weekly GS-1720/GS-4182 FDC versus continuing BVY in virologically suppressed PWH at Weeks 48 and 96
5. Phase 3:To evaluate the safety and tolerability of oral weekly GS-1720/GS-4182 FDC at Weeks 48 and 96

Conditions and MedDRA coding

HIV-1 Infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Participants must meet all of the following inclusion criteria to be eligible for participation in this study: Participants 18 years of age or older and able to understand and give written informed consent.
2. Participants assigned male at birth and participants assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified methods of contraception.
3. Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 24 weeks before and at screening.
4. Receiving BVY for ≥ 24 weeks prior to screening.

Exclusion criteria 19

1. Participants who meet any of the following exclusion criteria are not eligible to be enrolled in this study: Prior use of, or exposure to LEN, GS-1720, or GS-4182.
2. History of virologic failure while on an integrase strand-transfer inhibitor (INSTI)-based regimen.
3. Documented INSTI resistance, specifically, resistance-associated mutations (RAMs) E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene.
4. Prior use of any Long Acting (LA) parenteral antiretrovirals (ARVs) such as monoclonal antibodies (mAbs) or broadly neutralizing antibodies (bNAbs) targeting HIV-1, injectable cabotegravir (including oral cabotegravir lead-in), or injectable rilpivirine.
5. Any of the following laboratory values at screening: a) CD4 cell count < 200 cells/mm3 at screening b) Glomerular filtration rate < 60 mL/min according to the Modification of Diet in Renal Disease formula c) Hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 1.5 × upper limit of normal (ULN) d) Direct bilirubin > 1.5 × ULN e) Platelets count < 50,000 cells/mm3 f) Hemoglobin < 8.0 g/dL
6. Active tuberculosis infection.
7. Active or occult hepatitis B virus (HBV) infection as defined below (regardless of other HBV serologic results). Participants found to be susceptible to HBV infection should be recommended to receive an HBV vaccination. a) Hepatitis B surface antigen positive (HBsAg+) (or) b) Hepatitis B core antibody positive (HBcAb+) and hepatitis B surface antibody negative (HBsAb-).
8. Active hepatitis C virus (HCV) defined as detectable HCV RNA. Note: Participants with prior/inactive HCV infection (defined as undetectable HCV RNA) may enroll.
9. Moderate/severe hepatic impairment or a history of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).
10. Current alcohol or substance use judged by the investigator to potentially interfere with participant study compliance.
11. Have been treated within 6 months of study screening or expected to receive during the study immunosuppressant therapies or chemotherapeutic agents (eg, chronic [at least 4 weeks] systemic steroids, immunoglobulins, and other immune- or cytokine-based therapies).
12. Participation in any other clinical study, including observational studies, without prior approval from the Sponsor is prohibited while participating in this study.
13. Positive serum pregnancy test at screening or positive pregnancy test at Day 1.
14. Participants with plans to breastfeed during the study period and within 60 days following the last dose of study drug.
15. Serious illness requiring hospitalizations within 30 days prior to screening and during the screening period or active malignancy requiring acute systemic treatment.
16. Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
17. Abnormal electrocardiogram (ECG) at the screening visit that is clinically significant as determined by the investigator.
18. Requirement for ongoing therapy with or prior use of any prohibited medications.
19. Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study or unable to comply with the dosing requirements, including medical history of psychotic disorder and/or use of antipsychotic medications prescribed for psychosis.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase 2: The proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 24 as determined by the United States (US) Food and Drug Administration (FDA)-defined snapshot algorithm
2. Phase 3: The proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 as determined by the US FDA-defined snapshot algorithm

Secondary endpoints 9

1. Phase 2: The proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Weeks 12 and 48 as determined by the US FDA-defined snapshot algorithm
2. Phase 2: The proportion of participants with HIV-1 RNA < 50 copies/mL at Weeks 12, 24, and 48 as determined by the US FDA-defined snapshot algorithm
3. Phase 2: The change from baseline in CD4+ T-cell count at Weeks 12, 24, and 48
4. Phase 2: The proportion of participants experiencing treatment-emergent adverse events (TEAEs), and treatment-emergent laboratory abnormalities through Weeks 12, 24, and 48
5. Phase 2: PK parameters (Cmax, Tmax, Ctau, and AUCtau, as applicable) of GS-1720 and lenacapavir (LEN)
6. Phase 3: The proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 as determined by the US FDA-defined snapshot algorithm
7. Phase 3: The proportion of participants with HIV-1 RNA < 50 copies/mL at Weeks 48 and 96 as determined by the US FDA-defined snapshot algorithm
8. Phase 3: The change from baseline in CD4+ T-cell count at Weeks 48 and 96
9. Phase 3: The proportion of participants experiencing TEAEs, and treatment-emergent laboratory abnormalities through Weeks 48 and 96

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Scientific contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Third parties 2

Locations

6 EU/EEA countries · 33 investigational sites

By country

Investigational sites

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 82 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications