Study Evaluating the Safety and Efficacy of Islatravir in Combination With Lenacapavir in Virologically Suppressed People With HIV

NCT ID: NCT05052996

Last Updated: 2026-02-04

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

142 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-05

Study Completion Date

2028-03-31

Brief Summary

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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.

Detailed Description

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Conditions

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HIV-1 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1 (ISL+LEN)

Participants will receive the following for at least 48 weeks:

* Day 1 and Day 2: ISL 40 and LEN 600 mg
* Day 8 and weekly thereafter (ie, every 7 days): ISL 20 mg and LEN 300 mg

Group Type EXPERIMENTAL

ISL

Intervention Type DRUG

Capsules administered orally without regard to food

LEN

Intervention Type DRUG

Tablets administered orally without regard to food

Cohort 1 (B/F/TAF to ISL+LEN)

Participants will receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily for at least 48 weeks

After 48 weeks, participants will switch from B/F/TAF to ISL+LEN

* ISL 40 and LEN 600 mg on Day 1 and Day 2
* ISL 20 mg and LEN 300 mg weekly

Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study.

Group Type EXPERIMENTAL

ISL

Intervention Type DRUG

Capsules administered orally without regard to food

LEN

Intervention Type DRUG

Tablets administered orally without regard to food

B/F/TAF

Intervention Type DRUG

Tablets administered orally without regard to food

Cohort 2 (ISL+LEN)

Participants will receive the following for at least 48 weeks

* Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg)
* Day 2: LEN only oral 600 mg (2 x 300 mg)
* Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg

Group Type EXPERIMENTAL

ISL

Intervention Type DRUG

Capsules administered orally without regard to food

LEN

Intervention Type DRUG

Tablets administered orally without regard to food

Cohort 2 (B/F/TAF to ISL+LEN)

Participants will receive B/F/TAF 50/200/25 mg once daily for at least 48 weeks.

Group Type EXPERIMENTAL

ISL

Intervention Type DRUG

Capsules administered orally without regard to food

LEN

Intervention Type DRUG

Tablets administered orally without regard to food

B/F/TAF

Intervention Type DRUG

Tablets administered orally without regard to food

Extension Phase Cohort 2 of ISL/LEN Fixed Dose Combination (FDC)

After 48 Weeks of randomized treatment, all participants will be given an option to participate in an Extension Phase to receive ISL+LEN or ISL/LEN FDC tablet (when available) until ISL/LEN becomes available or until the sponsor elects to discontinue the study, whichever occurs first.

Participants receiving ISL+LEN during the randomized phase will continue to take ISL + LEN weekly.

Participants receiving B/F/TAF during the randomized phase will switch to ISL+LEN:

* Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg)
* Day 2: LEN only oral 600 mg (2 x 300 mg)
* Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg

Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study.

All participants in the extension phase will be transitioned to weekly ISL/LEN FDC (Dose A) tablet when it becomes available.

Group Type EXPERIMENTAL

ISL/LEN FDC

Intervention Type DRUG

Tablets administered orally without regard to food

Interventions

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ISL

Capsules administered orally without regard to food

Intervention Type DRUG

LEN

Tablets administered orally without regard to food

Intervention Type DRUG

B/F/TAF

Tablets administered orally without regard to food

Intervention Type DRUG

ISL/LEN FDC

Tablets administered orally without regard to food

Intervention Type DRUG

Other Intervention Names

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GS-6207 Biktarvy®

Eligibility Criteria

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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.

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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Pacific Oaks Medical Group

Beverly Hills, California, United States

Site Status

Ruane Clinical Research Group, Inc

Los Angeles, California, United States

Site Status

Mills Clinical Research

Los Angeles, California, United States

Site Status

Hoag Medical Group - Newport Beach

Newport Beach, California, United States

Site Status

BIOS Clinical Research

Palm Springs, California, United States

Site Status

Optimus Medical Group

San Francisco, California, United States

Site Status

Public Health Institute at Denver Health

Denver, Colorado, United States

Site Status

Vivent Health

Denver, Colorado, United States

Site Status

Washington Health Institute

Washington D.C., District of Columbia, United States

Site Status

The George Washington University Medical Faculty Associates Inc.

Washington D.C., District of Columbia, United States

Site Status

CAN Community Health Care, Inc.

Fort Lauderdale, Florida, United States

Site Status

Midway Immunology and Research Center

Ft. Pierce, Florida, United States

Site Status

JEM Research Institute

Lake Worth, Florida, United States

Site Status

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, United States

Site Status

Floridian Clinical Research

Miami Lakes, Florida, United States

Site Status

Orlando Immunology Center

Orlando, Florida, United States

Site Status

Emory University Hospital Midtown Infectious Disease Clinic

Atlanta, Georgia, United States

Site Status

Atlanta ID Group, PC

Atlanta, Georgia, United States

Site Status

Metro Infectious Disease Consultants

Decatur, Georgia, United States

Site Status

Chatham County Health Department

Savannah, Georgia, United States

Site Status

John A. Burns School of Medicine, University of Hawaii Clinics at Kaka'ako

Honolulu, Hawaii, United States

Site Status

Howard Brown Health Center

Chicago, Illinois, United States

Site Status

Northstar Healthcare

Chicago, Illinois, United States

Site Status

Indiana CTSI Clinical Research Center

Indianapolis, Indiana, United States

Site Status

Boston Medical Center

Boston, Massachusetts, United States

Site Status

AccessHealth MA

Boston, Massachusetts, United States

Site Status

Be Well Medical Center

Berkley, Michigan, United States

Site Status

Hennepin Healthcare HCMC

New Brighton, Minnesota, United States

Site Status

Southampton Healthcare, Inc.

St Louis, Missouri, United States

Site Status

Huntridge Family Clinic

Las Vegas, Nevada, United States

Site Status

ID Care

Hillsborough, New Jersey, United States

Site Status

AXCES Research Group

Santa Fe, New Mexico, United States

Site Status

New York-Presbyterian Queens

Flushing, New York, United States

Site Status

Jacobi Medical Center

The Bronx, New York, United States

Site Status

NC TraCS Institute - CTRC: University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Penn Medicine: Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Philadelphia FIGHT Community Health Centers

Philadelphia, Pennsylvania, United States

Site Status

Central Texas Clinical Research, LLC

Austin, Texas, United States

Site Status

AIDS Arms Inc

Dallas, Texas, United States

Site Status

North Texas Infectious Diseases Consultants, P.A.

Dallas, Texas, United States

Site Status

The Crofoot Research Center, INC

Houston, Texas, United States

Site Status

Peter Shalit, M.D.

Seattle, Washington, United States

Site Status

MultiCare Rockwood Main Clinic

Spokane, Washington, United States

Site Status

Community Health Care

Tacoma, Washington, United States

Site Status

Countries

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United States

References

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Colson AE, Crofoot GE, Ruane PJ, Ramgopal MN, Dretler AW, Nahass RG, Sinclair GI, Berhe M, Roberts A, Applin S, Brinson C, Jayaweera D, Workowski KA, Shihadeh F, Liu SY, Klopfer S, Llamoso C, Madera S, Dvory-Sobol H, Rhee MS, Rhee EG, Baeten JM, Eron JJ. Once-Weekly Oral Islatravir Plus Lenacapavir Versus Daily Oral Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Persons With HIV-1 : A Phase 2 Randomized Study. Ann Intern Med. 2025 Dec 23. doi: 10.7326/ANNALS-25-01939. Online ahead of print.

Reference Type DERIVED
PMID: 41429026 (View on PubMed)

Provided Documents

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Document Type: Study Protocol: Protocol Amendment 6

View Document

Document Type: Study Protocol: Protocol Amendment 5

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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GS-US-563-6041

Identifier Type: -

Identifier Source: org_study_id

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