A Study of Islatravir (MK-8591) in Trans and Gender Diverse Participants (MK-8591-035)

A Phase 2 Open-Label Study to Evaluate the Safety and Pharmacokinetics of Oral Islatravir Once-Monthly in Trans and Gender Diverse Individuals on Gender-Affirming Hormone Therapy and at Low-Risk for HIV-1 Infection

The primary objective of this study is to evaluate the safety and tolerability of Islatravir (ISL) in trans and gender diverse (TGD) participants who are receiving gender-affirming hormone therapy (GAHT) and are at low-risk for human immunodeficiency virus 1 (HIV-1) infection.

Study Overview

• Status: Withdrawn
• Conditions: Human Immunodeficiency Virus (HIV) Infections
• Intervention / Treatment: Drug: Islatravir

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Is confirmed HIV-uninfected based on negative HIV-1/HIV-2 test result before allocation to study intervention.
• Is on stable GAHT and does not intend to change therapy through Week 4 of the study.
• Has a low-risk of HIV infection.
• Identifies with a gender that is different from that assigned at birth.
• A participant assigned female at birth is eligible if not pregnant or chest-feeding and is not of childbearing potential (POCBP) or: Is a POCBP and using an acceptable contraceptive method, or be abstinent from penile-vaginal intercourse with an individual capable of producing sperm (abstinent on a long term and persistent basis); a POCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before the first dose of study intervention; If a urine test cannot be confirmed as negative (e.g, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive; the investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a participant assigned female at birth with an early undetected pregnancy; contraceptive use by participant assigned female at birth should be consistent with local regulations.

Exclusion Criteria:

• Has known current or chronic history of liver disease (e.g, non-alcoholic or alcoholic steatohepatitis) or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome, asymptomatic gallstones, or cholecystectomy), unless the participant has stable liver function tests and no evidence of hepatic synthetic dysfunction.
• Has a history of malignancy within 5 years of screening except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or in situ anal cancers.
• Has taken cabotegravir, lenacapavir, or any other long-acting HIV prevention product at any time (past or current use).
• Is currently participating in or has participated in a clinical study with an investigational compound or device, within 30 days before Day 1 through the duration of the study.
• Is expecting to conceive or donate eggs at any time during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Islatravir; 60 mg Islatravir taken orally in tablet form once monthly for up to 24 weeks	Drug: Islatravir; 60 mg Islatravir taken orally in tablet form once monthly for up to 24 weeks; Other Names: MK-8591

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants with one or more adverse events (AEs)	Number of participants with one or more AEs will be reported.	Up to 26 weeks
Participants with an AE leading to discontinuation of study intervention	Number of participants with an AE leading to discontinuation of study intervention will be reported.	Up to 20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve (AUC) of plasma islatravir (ISL)	Area Under the Curve from time 0 to 672 hours post-dose (AUC0-672hr) of plasma islatravir (ISL) will be reported.	Pre-dose on Day 1; any time on Weeks 1, 2 and 3; pre-dose on Weeks 4, 8, 12, 16, 20; any time on Week 24
Maximum concentration (Cmax) of plasma ISL	Maximum concentration (Cmax) of plasma ISL will be reported.	Pre-dose on Day 1; any time on Weeks 1, 2 and 3; pre-dose on Weeks 4, 8, 12, 16, 20; any time on Week 24
Trough concentration (Ctrough) of plasma ISL	Trough concentration (Ctrough) of plasma ISL will be reported.	Pre-dose on Day 1; any time on Weeks 1, 2 and 3; pre-dose on Weeks 4, 8, 12, 16, 20; any time on Week 24
Apparent terminal half-life (t1/2) of plasma ISL	Apparent terminal half-life (t1/2) of plasma ISL will be reported.	Pre-dose on Day 1; any time on Weeks 1, 2 and 3; pre-dose on Weeks 4, 8, 12, 16, 20; any time on Week 24

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Anticipated): October 17, 2022
• Primary Completion (Anticipated): March 25, 2024
• Study Completion (Anticipated): March 25, 2024

Study Registration Dates

• First Submitted: November 10, 2021
• First Submitted That Met QC Criteria: November 10, 2021
• First Posted (Actual): November 22, 2021

Study Record Updates

• Last Update Posted (Actual): October 17, 2022
• Last Update Submitted That Met QC Criteria: October 13, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Retroviral Agents; Islatravir
• Other Study ID Numbers: 8591-035; MK-8591-035 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No