Clinical trial NCT04003103: Safety and Pharmacokinetics of Oral Islatravir (MK-8591) Once Monthly in Participants at Low Risk of Human Immunodeficiency Virus 1 (HIV-1) Infection (MK-8591-016)
Official title: A Phase 2a, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral MK-8591 Once-Monthly in Participants at Low- Risk for HIV-1 Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-07-01
Enrollment: 242
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study will evaluate the safety, tolerability and pharmacokinetics (PK) of 6 once-monthly doses of oral islatravir (60 mg and 120 mg) compared with placebo in adults at low risk of HIV-1 infection

Detailed description: This study is ongoing for collection of safety follow-up of infants born to mothers participating in the study. The present results are based on the Week 68 interim analysis.

Eligibility criteria: Inclusion Criteria:

* Is in general good health with acceptable laboratory values at screening
* Is confirmed HIV-uninfected based on negative HIV-1/HIV-2 test result before randomization
* Has low risk of HIV infection, within 12 months prior to screening visit or the rescreening visit (if applicable)
* Use contraceptives consistent with local regulations
* Female is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP)
* A WOCBP is using an acceptable contraceptive method, or is abstinent from heterosexual intercourse as their preferred and usual lifestyle; or has a negative pregnancy test.

Exclusion Criteria:

* Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
* Has an active diagnosis of hepatitis due to any cause
* Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
* Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies from 30 days prior to Day

  1 through the duration of the study.
* Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 30 days prior to Day1 through the duration of the study.
* Has previously been randomized in a study and received islatravir (MK-8591).
* Female is expecting to conceive or donate eggs at any time during the study
* Has QTc interval (using Fridericia correction) \>450 msec (for males) or \>460 msec (for females) or deemed clinically abnormal by the investigator.

Primary outcomes:
measure: Number of Participants With ≥1 Adverse Event (AE) Through Week 36
timeFrame: Up to 36 weeks
measure: Number of Participants Discontinuing From Study Therapy Due to AE
timeFrame: Up to 20 weeks
measure: Number of Participants Discontinuing From Study Therapy Due to ≥1 Drug-related AE
timeFrame: Up to 20 weeks
measure: Number of Participants With ≥1 Drug-related AE Through Week 36
timeFrame: Up to 36 weeks
measure: Number of Participants With ≥1 Serious Adverse Event (SAE) Through Week 36
timeFrame: Up to 36 weeks
measure: Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 36
timeFrame: Up to 36 weeks
measure: Number of Participants With ≥1 Drug-related SAE Through Week 36
timeFrame: Up to 36 weeks
measure: Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 36
timeFrame: Up to 36 weeks
measure: Number of Participants With an AE Resulting in Death Through Week 36
timeFrame: Up to 36 weeks
Secondary outcomes:
measure: Area Under the Plasma Concentration-time Curve From Dosing to 672 Hours Postdose (AUC0-672) of Plasma ISL
timeFrame: Day 1 and Day 140: predose and 30-min postdose. On Day 2 collect ~24 hours after Day 1 dose. On Weeks 4, 8, 12 and 16, collect predose. Weeks 1, 2, 3, 21, 22, 23 and 24: collect at any time during the study visit.
measure: Maximum Plasma Concentration (Cmax) of ISL
timeFrame: Day 1 and Week 20, collect predose and 30-min postdose. On Day 2 collect ~24 hours after Day 1 dose. On Weeks 4, 8, 12 and 16, collect predose. Weeks 1, 2, 3, 21, 22, 23 and 24: collect at any time during the study visit.
measure: Trough Plasma Concentration (Ctrough) of ISL
timeFrame: Day 1 and Week 20: predose and 30-min postdose. Day 2: 24 hours post Day 1 dose. Weeks 1, 2, 3, 21, 22, 23 and 24: any time during the study visit. Weeks 4, 8, 12 and 16: predose.
measure: Apparent Plasma Terminal Half-life (t1/2) of ISL
timeFrame: Day 1 and Week 20, collect predose and 30-min postdose. On Day 2 collect ~24 hours after Day 1 dose. On Weeks 4, 8, 12 and 16, collect predose. Weeks 1, 2, 3, 21, 22, 23 and 24: collect at any time during the study visit.
measure: Number of Participants With ≥1 AE Through Week 24
timeFrame: Up to 24 weeks
measure: Number of Participants With ≥1 Drug-related AE Through Week 24
timeFrame: Up to 24 weeks
measure: Number of Participants With ≥1 SAE Through Week 24
timeFrame: Up to 24 weeks
measure: Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 24
timeFrame: Up to 24 weeks
measure: Number of Participants With ≥1 Drug-related SAE Through Week 24
timeFrame: Up to 24 weeks
measure: Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 24
timeFrame: Up to 24 weeks
measure: Number of Participants With an AE Resulting in Death Through Week 24
timeFrame: Up to 24 weeks
Other outcomes:
Locations:
city: Hollywood
country: United States
facility: Research Centers of America, LLC ( Site 0007)
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine - Drug Development Unit ( Site 0002)
state: Maryland
city: Lincoln
country: United States
facility: Celerion, Inc. ( Site 0006)
state: Nebraska
city: Pittsburgh
country: United States
facility: Magee Womens Research Institute ( Site 0001)
state: Pennsylvania
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Jerusalem ( Site 0016)
state: Yerushalayim
city: Haifa
country: Israel
facility: Rambam Medical Center ( Site 0017)
city: Bloemfontein
country: South Africa
facility: JOSHA Research ( Site 0015)
state: Free State
city: Johannesburg
country: South Africa
facility: Clinical HIV Research Unit CHRU ( Site 0014)
state: Gauteng
city: Cape Town
country: South Africa
facility: Emavundleni Vaccine Centre ( Site 0011)
state: Western Cape
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Devanathan AS, Cottrell ML. Pharmacology of HIV Cure: Site of Action. Clin Pharmacol Ther. 2021 Apr;109(4):841-855. doi: 10.1002/cpt.2187. Epub 2021 Mar 5.