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)

HIV-1 Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04003103
• Other study ID #: 8591-016
• Secondary ID: Merck Protocol N
• Status: Completed
• Phase: Phase 2
• Start date: September 19, 2019
• Est. completion date: November 24, 2022

Study information

• Verified date: April 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 242
• Est. completion date: November 24, 2022
• Est. primary completion date: March 18, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• HIV-1 Infection
• Infections

Intervention

Drug:
• Islatravir
Islatravir 30 mg capsules taken by mouth.
• Placebo
Placebo capsules taken by mouth.

Locations

Country	Name	City	State
Israel	Rambam Medical Center ( Site 0017)	Haifa
Israel	Hadassah Ein Karem Jerusalem ( Site 0016)	Jerusalem	Yerushalayim
South Africa	JOSHA Research ( Site 0015)	Bloemfontein	Free State
South Africa	Emavundleni Vaccine Centre ( Site 0011)	Cape Town	Western Cape
South Africa	Clinical HIV Research Unit CHRU ( Site 0014)	Johannesburg	Gauteng
United States	Johns Hopkins School of Medicine - Drug Development Unit ( Site 0002)	Baltimore	Maryland
United States	Research Centers of America, LLC ( Site 0007)	Hollywood	Florida
United States	Celerion, Inc. ( Site 0006)	Lincoln	Nebraska
United States	Magee Womens Research Institute ( Site 0001)	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Israel,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With =1 Adverse Event (AE) Through Week 36	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to 36 weeks
Primary	Number of Participants Discontinuing From Study Therapy Due to AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to 20 weeks
Primary	Number of Participants Discontinuing From Study Therapy Due to =1 Drug-related AE	A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study therapy.	Up to 20 weeks
Primary	Number of Participants With =1 Drug-related AE Through Week 36	A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study intervention.	Up to 36 weeks
Primary	Number of Participants With =1 Serious Adverse Event (SAE) Through Week 36	An SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event.	Up to 36 weeks
Primary	Number of Participants With a =1 Grade 3 to Grade 5 AE up to Week 36	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study therapy, whether or not considered related to the study intervention. Toxicity grading was according to the National Institutes of Health Division of AIDS (NIH DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events version 2.1 (Grade 3 is 'severe'; Grade 4 is 'potentially life-threatening'; and Grade 5 'results in death').	Up to 36 weeks
Primary	Number of Participants With =1 Drug-related SAE Through Week 36	An drug-related SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event, that is considered related to study therapy.	Up to 36 weeks
Primary	Number of Participants With =1 Drug-related Grade 3 to 5 AE Through Week 36	A drug-related Grade 3 to Grade 5 AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention; has a toxicity Grade 3 (severe), 4 (potentially life-threatening), or 5 (results in death); and is considered related to study therapy. Toxicity grading was according to the NIH DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (v. 2.1).	Up to 36 weeks
Primary	Number of Participants With an AE Resulting in Death Through Week 36	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to 36 weeks
Secondary	Area Under the Plasma Concentration-time Curve From Dosing to 672 Hours Postdose (AUC0-672) of Plasma ISL	The AUC0-672 of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.	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.
Secondary	Maximum Plasma Concentration (Cmax) of ISL	The Cmax of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.	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.
Secondary	Trough Plasma Concentration (Ctrough) of ISL	The plasma Ctrough of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.	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.
Secondary	Apparent Plasma Terminal Half-life (t1/2) of ISL	The plasma t1/2 of ISL after dosing on Day 140 is reported. Only ISL-treated participants are included in the PK analysis.	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.
Secondary	Number of Participants With =1 AE Through Week 24	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to 24 weeks
Secondary	Number of Participants With =1 Drug-related AE Through Week 24	A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study intervention.	Up to 24 weeks
Secondary	Number of Participants With =1 SAE Through Week 24	An SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event.	Up to 24 weeks
Secondary	Number of Participants With a =1 Grade 3 to Grade 5 AE up to Week 24	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study therapy, whether or not considered related to the study intervention. Toxicity grading was according to the National Institutes of Health Division of AIDS (NIH DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events version 2.1 (Grade 3 is 'severe'; Grade 4 is 'potentially life-threatening'; and Grade 5 'results in death').	Up to 24 weeks
Secondary	Number of Participants With =1 Drug-related SAE Through Week 24	An drug-related SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event, that is considered related to study therapy.	Up to 24 weeks
Secondary	Number of Participants With =1 Drug-related Grade 3 to 5 AE Through Week 24	A drug-related Grade 3 to Grade 5 AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention; has a toxicity Grade 3 (severe), 4 (potentially life-threatening), or 5 (results in death); and is considered related to study therapy. Toxicity grading was according to the NIH DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (v. 2.1).	Up to 24 weeks
Secondary	Number of Participants With an AE Resulting in Death Through Week 24	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to 24 weeks