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

• ClinicalTrials.gov Identifier: NCT04150068
• Recruitment Status: Active, not recruiting
• First Posted: November 4, 2019
• Last Update Posted: February 8, 2021
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: October 28, 2019
• First Posted Date: November 4, 2019
• Last Update Posted Date: February 8, 2021
• Actual Study Start Date: November 21, 2019
• Actual Primary Completion Date: October 5, 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 31, 2019): Proportion of Participants in Cohort 1 Achieving ≥ 0.5 log10 Copies/mL Reduction from Baseline in HIV-1 RNA at the End of Functional Monotherapy Period. [ Time Frame: Up to 15 days ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 31, 2019)

• Proportion of Participants in Cohort 1 with Plasma HIV-1 RNA < 50 Copies/mL at Week 26 Based on the US FDA-defined Snapshot Algorithm. [ Time Frame: Week 26 ]
• Proportion of Participants in Cohort 1 with Plasma HIV-1 RNA < 200 Copies/mL at Week 26 Based on the US FDA-defined Snapshot Algorithm. [ Time Frame: Week 26 ]
• Proportion of Participants in Cohort 1 with Plasma HIV-1 RNA < 50 Copies/mL at Week 52 Based on the US FDA-defined Snapshot Algorithm. [ Time Frame: Week 52 ]
• Proportion of Participants in Cohort 1 with Plasma HIV-1 RNA < 200 Copies/mL at Week 52 Based on the US FDA-defined Snapshot Algorithm. [ Time Frame: Week 52 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Safety and Efficacy of Lenacapavir in Combination With an Optimized Background Regimen in Heavily Treatment Experienced Participants Living With HIV-1 Infection With Multidrug Resistance
• Official Title: A Phase 2/3 Study to Evaluate the Safety and Efficacy of Long Acting Capsid Inhibitor GS-6207 in Combination With an Optimized Background Regimen in Heavily Treatment Experienced People Living With HIV-1 Infection With Multidrug Resistance
• Brief Summary: 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 living with HIV (PLWH) with multi-drug resistance (MDR).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Participants will be enrolled into Cohort 2 if Cohort 1 is fully enrolled or if they do not meet the criteria for randomization in Cohort 1.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Knowledge of treatment assignments will be masked during the Functional Monotherapy Period in Cohort 1.

Primary Purpose: Treatment

• Condition: HIV-1-infection

Intervention

• Drug: Oral Lenacapavir
  Tablets administered without regard to food
  Other Name: GS-6207
• Drug: Placebo oral tablet
  Tablets administered without regard to food
• Drug: Subcutaneous Lenacapavir
  Administered in the abdomen via subcutaneous injections
  Other Name: GS-6207
• Drug: Failing ARV Regimen
  Failing antiretroviral regimen defined by the lack of efficacy. Any combination of approved and unapproved agents that could potentially be part of the failing regimen.
• Drug: Optimized Background Regimen (OBR)
  Optimized background regimen as prescribed by the Investigator

Study Arms

• Experimental: Cohort 1A Lenacapavir, Failing ARV Regimen, and OBR

  Functional Monotherapy Period: Participants will receive oral lenacapavir 600 mg, 600mg, and 300 mg tablets on Days 1, 2, and 8 respectively while continuing their failing regimen (previous Antiretroviral (ARV) regimen).

  Maintenance Period: At Day 1 SC (14 days after the first dose of oral lenacapavir), participants will receive subcutaneous (SC) lenacapavir 927 mg and initiate an optimized background regimen (OBR) (as prescribed by the Investigator). Participants will continue to receive SC lenacapavir 927 mg once every 6 months (26 weeks).

  Participants willing to continue beyond the study beyond Week 52 visit will receive SC lenacapavir every 6 months (26 weeks) starting at Week 52 visit, while continuing their OBR.

  Interventions:

  • Drug: Oral Lenacapavir
  • Drug: Subcutaneous Lenacapavir
  • Drug: Failing ARV Regimen
  • Drug: Optimized Background Regimen (OBR)
• Placebo Comparator: Cohort 1B: Placebo, Lenacapavir, Failing ARV Regimen, and OBR

  Cohort 1B:

  Functional Monotherapy Period: Participants will receive placebo on Days 1, 2, and 8 while continuing their failing regimen.

  Maintenance Period: At Day 15, participants will receive oral lenacapavir 600 mg and initiate an OBR (as prescribed by the Investigator). Participants will receive oral lenacapavir 600 mg and 300 mg at Day 16 and Day 22, respectively. At Day 1 SC (14 days after the first dose of oral lenacapavir), participants will receive SC lenacapavir 927 mg while continuing their optimized background regimen. Participants will continue to receive SC lenacapavir 927 mg once every 6 months (26 weeks).

  Participants willing to continue beyond the study beyond Week 52 visit will receive SC lenacapavir every 6 months (26 weeks) starting at Week 52 visit, while continuing their OBR.

  Interventions:

  • Drug: Oral Lenacapavir
  • Drug: Placebo oral tablet
  • Drug: Subcutaneous Lenacapavir
  • Drug: Failing ARV Regimen
  • Drug: Optimized Background Regimen (OBR)
• Experimental: Cohort 2: Lenacapavir and OBR

  Oral Lead-in Period: At Day 1, participants will receive oral lenacapavir 600 mg and initiate an OBR (as prescribed by the Investigator). Participants will receive oral lenacapavir 600 mg and 300 mg at Day 2 and Day 8, respectively, while continuing their OBR.

  Maintenance Period: At Day 1 SC (14 days after the first dose of oral lenacapavir), participants will receive SC lenacapavir 927 mg once every 6 months (26 weeks).

  Participants willing to continue beyond the study beyond Week 52 visit will receive SC lenacapavir every 6 months (26 weeks) starting at Week 52 visit, while continuing their OBR.

  Interventions:

  • Drug: Oral Lenacapavir
  • Drug: Subcutaneous Lenacapavir
  • Drug: Optimized Background Regimen (OBR)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 5, 2021): 72
• Original Estimated Enrollment (submitted: October 31, 2019): 100
• Estimated Study Completion Date: October 2023
• Actual Primary Completion Date: October 5, 2020 (Final data collection date for primary outcome measure)

Eligibility 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 antiretroviral (ARV) regimen for > 8 weeks
• Have HIV-1 RNA ≥ 400 copies/mL at screening
• Have multidrug resistance
• 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 optimized background regimen together with lenacapavir
• No Hepatitis C virus (HCV) ongoing infection

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Dominican Republic, France, Germany, Italy, Japan, South Africa, Spain, Taiwan, Thailand, United States

Administrative Information

• NCT Number: NCT04150068
• Other Study ID Numbers: GS-US-200-4625; 2019-003814-16 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: February 2021