Clinical trial NCT04143594: Study to Evaluate the Safety and Efficacy of Lenacapavir (GS-6207) in Combination With Other Antiretroviral Agents in People Living With HIV
Official title: A Phase 2 Randomized, Open Label, Active Controlled Study Evaluating the Safety and Efficacy of Long-acting Capsid Inhibitor GS-6207 in Combination With Other Antiretroviral Agents in People Living With HIV
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1-infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2019-10-29
Enrollment: 183
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the efficacy of lenacapavir (formerly GS-6207) containing regimens in people living with human immunodeficiency virus (HIV) (PLWH).


Eligibility criteria: Key Inclusion Criteria:

* Antiretroviral (ARV) naive with no use of any ARV within one month of screening. Use of pre-exposure prophylaxis (PrEP) (any duration), post-exposure prophylaxis (PEP) (any duration), or HIV-1 treatment (\< 10 days therapy total) \> 1 month prior to screening is permitted
* HIV-1 ribonucleic acid (RNA) ≥ 200 copies/mL at screening
* Cluster Determinant 4+ (CD4+) cell count ≥ 200 cells/microliter at screening

Key Exclusion Criteria:

* Current Hepatitis B Virus (HBV) or Hepatitis C virus (HCV) infection

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

Primary outcomes:
measure: Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 54 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm
timeFrame: Week 54
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 28 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 28
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 38 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 38
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 80 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 80
measure: Change From Baseline in Log10 HIV-1 RNA at Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline in Log10 HIV-1 RNA at Week 38
timeFrame: Baseline, Week 38
measure: Change From Baseline in Log10 HIV-1 RNA at Week 54
timeFrame: Baseline, Week 54
measure: Change From Baseline in Log10 HIV-1 RNA at Week 80
timeFrame: Baseline, Week 80
measure: Change From Baseline in Clusters of Differentiation 4+ (CD4+) Cell Count at Week 28
timeFrame: Baseline, Week 28
measure: Change From Baseline in CD4+ Cell Count at Week 38
timeFrame: Baseline, Week 38
measure: Change From Baseline in CD4+ Cell Count at Week 54
timeFrame: Baseline, Week 54
measure: Change From Baseline in CD4+ Cell Count at Week 80
timeFrame: Baseline, Week 80
measure: Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 174.9 weeks
measure: Percentage of Participants Who Experienced Maximum Postbaseline Laboratory Abnormalities
timeFrame: Up to 174.9 weeks
measure: Pharmacokinetics (PK) of LEN: Plasma LEN Pre-dose Concentrations for SC LEN
timeFrame: Day 2, 8, Day 1 SC (Day 15), Week 28 and Week 54
measure: PK of LEN : Plasma LEN Single Anytime Concentrations for the Oral LEN + DVY
timeFrame: Day 2, 8, 15 , Week 28 and Week 54
measure: PK of TAF (Tenofovir Alafenamide) and TFV (Tenofovir): Area Under the Concentration Versus Time Curve (AUClast) on Day 1
timeFrame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1
measure: PK of TAF and TFV (Tenofovir): Maximum Observed Concentration of Drug (Cmax) on Day 1
timeFrame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1
measure: PK of TAF and TFV: Time (Observed Time Point) of Cmax (Tmax) on Day 1
timeFrame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1
measure: PK of TFV: Last Observed Quantifiable Concentration of the Drug (Clast) on Day 1
timeFrame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose on Day 1
measure: PK of TAF and TFV: AUClast at Weeks 16, 22, or 28
timeFrame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
measure: PK of TAF and TFV: Cmax at Weeks 16, 22, or 28
timeFrame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
measure: PK of TAF and TFV: Tmax at Weeks 16, 22, or 28
timeFrame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
measure: PK of TFV: Clast at Weeks 16, 22, or 28
timeFrame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
measure: PK of TAF: AUClast at Week 38
timeFrame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
measure: PK of TAF: Cmax at Week 38
timeFrame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
measure: PK of TAF: Tmax at Week 38
timeFrame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
measure: PK of Tenofovir Diphosphate (TFV-DP): AUClast at Weeks 4, 10, 16, or 22
timeFrame: 0 hours (Predose) and at 1, 2, and 6 hours postdose
measure: PK of TFV-DP: Cmax at Weeks 4, 10, 16, or 22
timeFrame: 0 hours (Predose) and at 1, 2, and 6 hours postdose
measure: PK of TFV-DP: Tmax at Weeks 4, 10, 16, or 22
timeFrame: 0 hours (Predose) and at 1, 2, and 6 hours postdose
measure: PK of Bictegravir (BIC): AUClast at Week 38
timeFrame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
measure: PK of BIC: Cmax at Week 38
timeFrame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
measure: PK of BIC: Tmax at Week 38
timeFrame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
measure: PK of BIC: Clast at Week 38
timeFrame: 0 hours (Predose) and at 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Valleywise Community Health Center - McDowell
state: Arizona
city: Phoenix
country: United States
facility: Pueblo Family Physicians
state: Arizona
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group Inc
state: California
city: Los Angeles
country: United States
facility: Mills Clinical Research at Men's Health Foundation
state: California
city: Palm Springs
country: United States
facility: Eisenhower Health Center at Rimrock
state: California
city: Aurora
country: United States
facility: University of Colorado, Denver, University of Colorado Hospital
state: Colorado
city: Denver
country: United States
facility: Denver Public Health
state: Colorado
city: New Haven
country: United States
facility: Yale University; School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Whitman-Walker Institute, Inc.
state: District of Columbia
city: Washington
country: United States
facility: Washington Health Institute
state: District of Columbia
city: DeLand
country: United States
facility: Midland Florida Clinical Research Center, LLC
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Hialeah
country: United States
facility: Floridian Clinical Research
state: Florida
city: Miami Beach
country: United States
facility: AIDS Healthcare Foundation - South Beach
state: Florida
city: Miami
country: United States
facility: AHF-The Kinder Medical Group
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Hospital Comprehensive Research Institute
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A.
state: Florida
city: Atlanta
country: United States
facility: Atlanta ID Group, PC
state: Georgia
city: Augusta
country: United States
facility: August University Medical Center
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Macon
country: United States
facility: Mercer University, Department of Internal Medicine
state: Georgia
city: Savannah
country: United States
facility: Chatham County Health Department
state: Georgia
city: Chicago
country: United States
facility: Howard Brown Health Center
state: Illinois
city: Chicago
country: United States
facility: Northstar Healthcare
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Infectious Diseases Research
state: Indiana
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Southfield
country: United States
facility: St. John Newland Medical Associates
state: Michigan
city: Kansas City
country: United States
facility: KC CARE Health Center
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: AHF-Midtown
state: New York
city: Greenville
country: United States
facility: East Carolina University, The Brody School of Medicine
state: North Carolina
city: Huntersville
country: United States
facility: Rosedale Infectious Diseases
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Clinical Research Site/University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Bellaire
country: United States
facility: St Hope Foundation
state: Texas
city: Dallas
country: United States
facility: Prism Health North Texas
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants, P.A.
state: Texas
city: Fort Worth
country: United States
facility: Texas Centers for Infectious Disease Associates
state: Texas
city: Houston
country: United States
facility: The Crofoot Research Center, Inc.
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Annandale
country: United States
facility: Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)
state: Virginia
city: Seattle
country: United States
facility: Peter Shalit, M.D.
state: Washington
city: Spokane
country: United States
facility: MultiCare Rockwood HIV Critical Care Clinic
state: Washington
city: Santo Domingo
country: Dominican Republic
facility: Instituto Dominicano de Estudios Virológicos (IDEV)
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
city: San Juan
country: Puerto Rico
facility: HOPE Clinical Research
city: San Juan
country: Puerto Rico
facility: Proyecto ACTU, School of Medicine, University of Puerto Rico
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Gupta SK, Berhe M, Crofoot G, Benson P, Ramgopal M, Sims J, McDonald C, Ruane P, Sanchez WE, Scribner A, Liu SY, VanderVeen LA, Dvory-Sobol H, Rhee MS, Baeten JM, Koenig E. Lenacapavir administered every 26 weeks or daily in combination with oral daily antiretroviral therapy for initial treatment of HIV: a randomised, open-label, active-controlled, phase 2 trial. Lancet HIV. 2023 Jan;10(1):e15-e23. doi: 10.1016/S2352-3018(22)00291-0.
citation: VanderVeen, L. A., et al. Resistance Analysis of Long-Acting Lenacapavir in People With HIV Who are Treatment-Naïve After 80 Weeks of Treatment [Poster14]. European Meeting on HIV & Hepatitis 2023, Rome, Italy.
citation: Jogiraju V, Shelton M, Dheri P, Ling J, Wang H, Dvory-Sobol H, et al. Pharmacokinetics of Lenacapavir Alone and When Coadministered With Other Antiretrovirals in People With HIV [Poster PII-056]. American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting; 2023 22-24 March; Atlanta, GA.
citation: Hagins D, Koenig E, Safran R, Santiago L, Wohlfeiler M, Hsiao C, et al. Long-Acting Lenacapavir in a Combination Regimen for Treatment Naïve PWH: Week 80 [Poster 522]. Conference on Retroviruses and Opportunistic Infections (CROI); 2023 19-22 February; Seattle, WA.
citation: VanderVeen LA, Margot N, Naik V, Dvory-Sobol H, Rhee MS, Callebaut C. Resistance Analysis of Long-Acting Lenacapavir in Treatment-Naïve People With HIV at 54 Weeks [Poster EPB239]. AIDS 2022; 2022 29 July-2 August; Montreal, Quebec, Canada.
citation: Gupta SK, Sims J, Brinson C, Cruickshank FA, Oguchi G, Morales J, et al. Lenacapavir as part of a Combination Regimen in Treatment-Naïve People with HIV: Week 54 Results [Presentation]. Virtual Conference on Retroviruses and Opportunistic Infections (CROI) 2022; 2022 12-16 February.
citation: VanderVeen, L, Margot N, Naik V, et al. Interim Resistance Analysis of Long-Acting Lenacapavir in Treatment-Naïve People with HIV at 28 Weeks (CALIBRATE) [Abstract Oral 73]. Presented at: ID Week; 2021 September 29 - October 03.
citation: Gupta SK, Berhe M, Crofoot G, et al. Long-Acting Subcutaneous Lenacapavir Dosed Every 6 Months as part of a Combination Regimen in Treatment-Naïve People with HIV: Interim 16-week Results of a Randomized, Open-label, Phase 2 Induction-Maintenance Study (CALIBRATE) [Abstract OALB0302]. Presented at: International AIDS Society (IAS) Conference; 2021 July 18-21.
citation: Harris P, Henderson R, Hayward P. Highlights from the 11th IAS Conference on Science. Lancet HIV. 2021 Aug;8(8):e459. doi: 10.1016/S2352-3018(21)00161-2. No abstract available.