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

NCT05052996 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: GS-US-563-6041
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 44

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• 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

  The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 24 window was between Day 148 and 189 (inclusive). Percentages were rounded off.

  Week 24

Secondary Outcomes (19)

• Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm

  Week 12

• Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

  Week 48

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm

  Week 12

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm

  Week 24

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

  Week 48

Study Arms (5)

Cohort 1 (ISL+LEN)

EXPERIMENTAL

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

Drug: ISL; Drug: LEN

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

EXPERIMENTAL

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.

Drug: ISL; Drug: LEN; Drug: B/F/TAF

Cohort 2 (ISL+LEN)

EXPERIMENTAL

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

Drug: ISL; Drug: LEN

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

EXPERIMENTAL

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

Drug: ISL; Drug: LEN; Drug: B/F/TAF

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

EXPERIMENTAL

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.

Drug: ISL/LEN FDC

Interventions

ISL DRUG

Capsules administered orally without regard to food

Cohort 1 (B/F/TAF to ISL+LEN); Cohort 1 (ISL+LEN); Cohort 2 (B/F/TAF to ISL+LEN); Cohort 2 (ISL+LEN)

LEN DRUG

Tablets administered orally without regard to food

Also known as: GS-6207

Cohort 1 (B/F/TAF to ISL+LEN); Cohort 1 (ISL+LEN); Cohort 2 (B/F/TAF to ISL+LEN); Cohort 2 (ISL+LEN)

B/F/TAF DRUG

Tablets administered orally without regard to food

Also known as: Biktarvy®

Cohort 1 (B/F/TAF to ISL+LEN); Cohort 2 (B/F/TAF to ISL+LEN)

ISL/LEN FDC DRUG

Tablets administered orally without regard to food

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Gilead Sciences: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (44)

Pacific Oaks Medical Group

Beverly Hills, California, 90211, United States

Location

Ruane Clinical Research Group, Inc

Los Angeles, California, 90036, United States

Location

Mills Clinical Research

Los Angeles, California, 90069, United States

Location

Hoag Medical Group - Newport Beach

Newport Beach, California, 92663, United States

Location

BIOS Clinical Research

Palm Springs, California, 92262, United States

Location

Optimus Medical Group

San Francisco, California, 94102, United States

Location

Public Health Institute at Denver Health

Denver, Colorado, 80204, United States

Location

Vivent Health

Denver, Colorado, 80246, United States

Location

Washington Health Institute

Washington D.C., District of Columbia, 20017, United States

Location

The George Washington University Medical Faculty Associates Inc.

Washington D.C., District of Columbia, 20037, United States

Location

CAN Community Health Care, Inc.

Fort Lauderdale, Florida, 33316, United States

Location

Midway Immunology and Research Center

Ft. Pierce, Florida, 34982, United States

Location

JEM Research Institute

Lake Worth, Florida, 33462, United States

Location

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, 33136, United States

Location

Floridian Clinical Research

Miami Lakes, Florida, 33016, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

Emory University Hospital Midtown Infectious Disease Clinic

Atlanta, Georgia, 30308, United States

Location

Atlanta ID Group, PC

Atlanta, Georgia, 30309, United States

Location

Metro Infectious Disease Consultants

Decatur, Georgia, 30033, United States

Location

Chatham County Health Department

Savannah, Georgia, 31401, United States

Location

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

Honolulu, Hawaii, 96813, United States

Location

Howard Brown Health Center

Chicago, Illinois, 60613, United States

Location

Northstar Healthcare

Chicago, Illinois, 60657, United States

Location

Indiana CTSI Clinical Research Center

Indianapolis, Indiana, 46202, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

AccessHealth MA

Boston, Massachusetts, 02129, United States

Location

Be Well Medical Center

Berkley, Michigan, 48072, United States

Location

Hennepin Healthcare HCMC

New Brighton, Minnesota, 55112, United States

Location

Southampton Healthcare, Inc.

St Louis, Missouri, 63139, United States

Location

Huntridge Family Clinic

Las Vegas, Nevada, 89104, United States

Location

ID Care

Hillsborough, New Jersey, 08844, United States

Location

AXCES Research Group

Santa Fe, New Mexico, 87505, United States

Location

New York-Presbyterian Queens

Flushing, New York, 11355, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

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

Chapel Hill, North Carolina, 27599, United States

Location

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

Philadelphia, Pennsylvania, 19104, United States

Location

Philadelphia FIGHT Community Health Centers

Philadelphia, Pennsylvania, 19107, United States

Location

Central Texas Clinical Research, LLC

Austin, Texas, 78705, United States

Location

AIDS Arms Inc

Dallas, Texas, 75208, United States

Location

North Texas Infectious Diseases Consultants, P.A.

Dallas, Texas, 75246, United States

Location

The Crofoot Research Center, INC

Houston, Texas, 77098, United States

Location

Peter Shalit, M.D.

Seattle, Washington, 98104, United States

Location

MultiCare Rockwood Main Clinic

Spokane, Washington, 99202, United States

Location

Community Health Care

Tacoma, Washington, 98405, United States

Location

Related Publications (1)

• 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. 2026 Feb;179(2):168-176. doi: 10.7326/ANNALS-25-01939. Epub 2025 Dec 23.

  PMID: 41429026 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

lenacapavir; bictegravir, emtricitabine, tenofovir alafenamide, drug combination

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2021
• First Posted: September 22, 2021
• Study Start: October 5, 2021
• Primary Completion: December 19, 2023
• Study Completion (Estimated): March 1, 2028
• Last Updated: February 4, 2026
• Results First Posted: January 14, 2025

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (44)