Clinical trial NCT05052996: Study Evaluating the Safety and Efficacy of Islatravir in Combination With Lenacapavir in Virologically Suppressed People With HIV
Official title: A Phase 2 Randomized, Open-Label, Active-Controlled Study Evaluating the Safety and Efficacy of an Oral Weekly Regimen of Islatravir in Combination With Lenacapavir in Virologically Suppressed People With HIV
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: HIV-1 Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-09-22
Enrollment: 142
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 oral weekly islatravir (ISL) in combination with lenacapavir (LEN) in virologically suppressed people with HIV (PWH) at Week 24.


Eligibility criteria: Key Inclusion Criteria:

* Received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for ≥ 24 weeks at screening.
* Documented plasma human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) \< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) for ≥ 24 weeks before and at screening.
* Plasma HIV-1 RNA \< 50 copies/mL at screening.

Key Exclusion Criteria:

* History of prior virologic failure while receiving treatment for HIV-1.
* Prior use of, or exposure to, islatravir (ISL) or lenacapavir (LEN).
* Active, serious infections requiring parenteral therapy \< 30 days before randomization.
* Active or occult hepatitis B virus (HBV) coinfection, defined as hepatitis B core antibody (HBcAb) positive, hepatitis B surface antigen (HBsAg) positive, or HBV deoxyribonucleic acid (DNA) positive as determined by the central laboratory.
* Active hepatitis C virus (HCV) coinfection, defined as detectable HCV RNA.
* Any of the following laboratory values at screening:

  * Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gault formula
* CD4+ T-cells \< 200 cells/mm\^3 (Cohort 1); CD4+ T-cells \< 350 cells/mm\^3 (cohort 2).
* Absolute lymphocyte count \< 900 cells/mm\^3 (cohort 2).
* Individuals of childbearing potential (as defined in protocol) who have a positive serum pregnancy test at screening or positive urine and serum pregnancy tests at Day 1 prior to study drug administration.
* Individuals who plan to continue breastfeeding during the study.
* Documented historical or screening resistance reports showing nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) or non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs) resistance mutations in reverse transcriptase, including M184V/I (Cohort 2).

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

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 12
measure: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 48
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 12
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 24
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm
timeFrame: Week 48
measure: Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in CD4+ Cell Count at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in CD4+ Cell Count at Week 48
timeFrame: Baseline and Week 48
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation
timeFrame: Up to 5 years
measure: Cohort 1: Plasma Concentrations for ISL
timeFrame: Anytime postdose at Week 4
measure: Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of Islatravir (ISL)
timeFrame: Anytime post dose on Day 1 and at either Week 12 or Week 18
measure: Cohort 2: PK Parameter: Tmax of ISL
timeFrame: Anytime post dose on Day 1 and at either Week 12 or Week 18
measure: Cohort 2: PK Parameter: Ctau of ISL
timeFrame: Anytime post dose at either Week 12 or Week 18
measure: Cohort 2: PK Parameter: AUCtau of ISL
timeFrame: Anytime post dose at either Week 12 or Week 18
measure: Plasma Concentrations for LEN
timeFrame: Anytime postdose at Week 4
measure: Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of LEN
timeFrame: Anytime post dose on Day 1, Day 2 and at either Week 12 or 18
measure: Cohort 2: PK Parameter: Tmax of LEN
timeFrame: Anytime post dose on Day 1, Day 2 and at either Week 12 or Week 18
measure: Cohort 2: PK Parameter: Ctau of LEN
timeFrame: Anytime post dose at either Week 12 or Week 18
measure: Cohort 2: PK Parameter: AUCtau of LEN
timeFrame: Anytime post dose at either Week 12 or Week 18
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Pacific Oaks Medical Group
state: California
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group, Inc
state: California
city: Los Angeles
country: United States
facility: Mills Clinical Research
state: California
city: Newport Beach
country: United States
facility: Hoag Medical Group - Newport Beach
state: California
city: Palm Springs
country: United States
facility: BIOS Clinical Research
state: California
city: San Francisco
country: United States
facility: Optimus Medical Group
state: California
city: Denver
country: United States
facility: Public Health Institute at Denver Health
state: Colorado
city: Denver
country: United States
facility: Vivent Health
state: Colorado
city: Washington
country: United States
facility: Washington Health Institute
state: District of Columbia
city: Washington
country: United States
facility: The George Washington University Medical Faculty Associates Inc.
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: CAN Community Health Care, Inc.
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Lake Worth
country: United States
facility: JEM Research Institute
state: Florida
city: Miami Lakes
country: United States
facility: Floridian Clinical Research
state: Florida
city: Miami
country: United States
facility: Schiff Center for Liver Diseases/University of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital Midtown Infectious Disease Clinic
state: Georgia
city: Atlanta
country: United States
facility: Atlanta ID Group, PC
state: Georgia
city: Decatur
country: United States
facility: Metro Infectious Disease Consultants
state: Georgia
city: Savannah
country: United States
facility: Chatham County Health Department
state: Georgia
city: Honolulu
country: United States
facility: John A. Burns School of Medicine, University of Hawaii Clinics at Kaka'ako
state: Hawaii
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 CTSI Clinical Research Center
state: Indiana
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: AccessHealth MA
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: New Brighton
country: United States
facility: Hennepin Healthcare HCMC
state: Minnesota
city: Saint Louis
country: United States
facility: Southampton Healthcare, Inc.
state: Missouri
city: Las Vegas
country: United States
facility: Huntridge Family Clinic
state: Nevada
city: Hillsborough
country: United States
facility: ID Care
state: New Jersey
city: Santa Fe
country: United States
facility: AXCES Research Group
state: New Mexico
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Flushing
country: United States
facility: New York-Presbyterian Queens
state: New York
city: Chapel Hill
country: United States
facility: NC TraCS Institute - CTRC: University of North Carolina at Chapel Hill
state: North Carolina
city: Philadelphia
country: United States
facility: Penn Medicine: Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia FIGHT Community Health Centers
state: Pennsylvania
city: Austin
country: United States
facility: Central Texas Clinical Research, LLC
state: Texas
city: Dallas
country: United States
facility: AIDS Arms Inc
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants, P.A.
state: Texas
city: Houston
country: United States
facility: The Crofoot Research Center, INC
state: Texas
city: Seattle
country: United States
facility: Peter Shalit, M.D.
state: Washington
city: Spokane
country: United States
facility: MultiCare Rockwood Main Clinic
state: Washington
city: Tacoma
country: United States
facility: Community Health Care
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: