Study to Evaluate the Safety and Efficacy of Lenacapavir (GS-6207) in Combination With an Optimized Background Regimen (OBR) in Heavily Treatment Experienced Participants Living With HIV-1 Infection With Multidrug Resistance (CAPELLA)

Gilead Sciences

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: HIV-1-infection

Treatments: Drug: Optimized Background Regimen (OBR); Drug: Oral Lenacapavir Placebo; Drug: Subcutaneous Lenacapavir; Drug: Failing ARV Regimen; Drug: Oral Lenacapavir

Study type: Interventional

Funder types: Industry

Identifiers

NCT04150068

2019-003814-16 (EudraCT Number)

GS-US-200-4625

Details and patient eligibility

About

The primary objective of this study is to evaluate the antiviral activity of lenacapavir (formerly GS-6207) administered as an add-on to a failing regimen (functional monotherapy) in people with human immunodeficiency virus (HIV) (PWH) with multi-drug resistance (MDR).

Enrollment: 72 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Adult aged ≥ 18 years (at all sites) or adolescent aged ≥ 12 and weighing ≥ 35 kg (at sites in North America and Dominican Republic)
• Currently receiving a stable failing ARV regimen for > 8 weeks
• Have HIV-1 RNA ≥ 400 copies/mL at screening
• Have multidrug resistance (resistance to ≥2 agents from ≥3 of the 4 main classes of ARV)
• Have no more than 2 fully active ARV remaining from the 4 main classes that can be effectively combined to form a viable regimen
• Able and willing to receive an OBR together with lenacapavir
• No Hepatitis C virus (HCV) ongoing infection

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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72 participants in 3 patient groups, including a placebo group

Cohort 1A: Lenacapavir

Experimental group

Description:

Participants with HIV-1 ribonucleic acid (RNA) ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at Cohort Selection visit compared with screening visit will receive oral lenacapavir (LEN) 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, while continuing their failing regimen in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive subcutaneous (SC) LEN 927 mg and will initiate an optimized background regimen (OBR) at Day 1 SC Visit (14 days after the first dose of oral LEN). Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.

Treatment:

Drug: Oral Lenacapavir

Drug: Failing ARV Regimen

Drug: Subcutaneous Lenacapavir

Drug: Optimized Background Regimen (OBR)

Cohort 1B: Placebo to Lenacapavir

Placebo Comparator group

Description:

Participants with HIV-1 RNA ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at the Cohort Selection visit compared with screening visit will receive oral LEN placebo on Days 1, 2, and 8 while continuing their failing regimen in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive oral LEN 600 mg on Days 15 and 16 and 300 mg on Day 22, and will initiate an OBR on Day 15. At Day 1 SC (14 days after the first dose of oral LEN), participants will receive SC LEN 927 mg while continuing OBR. Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue study in the country.

Treatment:

Drug: Oral Lenacapavir

Drug: Failing ARV Regimen

Drug: Subcutaneous Lenacapavir

Drug: Oral Lenacapavir Placebo

Drug: Optimized Background Regimen (OBR)

Cohort 2: Lenacapavir

Experimental group

Description:

Participants with a ≥ 0.5 log10 copies/mL HIV-1 RNA decline at the Cohort Selection Visit compared with the screening visit or with HIV-1 RNA \< 400 copies/mL or if Cohort 1 is fully enrolled will receive oral LEN 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, and will initiate an OBR on Day 1 in Oral Lead-in Period (Baseline to Day 14); followed by Maintenance Period where participants will receive SC LEN 927 mg at Day 1 SC Visit (14 days after the first dose of oral LEN) while continuing their OBR. Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.

Treatment:

Drug: Oral Lenacapavir

Drug: Subcutaneous Lenacapavir

Drug: Optimized Background Regimen (OBR)