Back to resultsSafety 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)
Primary Purpose
HIV-1 Infection
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Islatravir
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for HIV-1 Infection
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.
Sites / Locations
- Research Centers of America, LLC ( Site 0007)
- Johns Hopkins School of Medicine - Drug Development Unit ( Site 0002)
- Celerion, Inc. ( Site 0006)
- Magee Womens Research Institute ( Site 0001)
- Hadassah Ein Karem Jerusalem ( Site 0016)
- Rambam Medical Center ( Site 0017)
- JOSHA Research ( Site 0015)
- Clinical HIV Research Unit CHRU ( Site 0014)
- Emavundleni Vaccine Centre ( Site 0011)
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Islatravir 60 mg
Islatravir 120 mg
Placebo
Arm Description
60 mg islatravir + placebo for islatravir administered once monthly, orally in capsule form for 24 weeks
120 mg islatravir administered once monthly, orally in capsule form for 24 weeks
Placebo for islatravir administered once monthly, orally in capsule form for 24 weeks
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
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').
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.
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).
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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').
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.
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).
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04003103
Brief Title
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
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
September 19, 2019 (Actual)
Primary Completion Date
March 18, 2022 (Actual)
Study Completion Date
November 24, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV-1 Infection
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
242 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Islatravir 60 mg
Arm Type
Experimental
Arm Description
60 mg islatravir + placebo for islatravir administered once monthly, orally in capsule form for 24 weeks
Arm Title
Islatravir 120 mg
Arm Type
Experimental
Arm Description
120 mg islatravir administered once monthly, orally in capsule form for 24 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo for islatravir administered once monthly, orally in capsule form for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Islatravir
Other Intervention Name(s)
MK-8591
Intervention Description
Islatravir 30 mg capsules taken by mouth.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo capsules taken by mouth.
Primary Outcome Measure Information:
Title
Number of Participants With ≥1 Adverse Event (AE) Through Week 36
Description
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.
Time Frame
Up to 36 weeks
Title
Number of Participants Discontinuing From Study Therapy Due to AE
Description
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.
Time Frame
Up to 20 weeks
Title
Number of Participants Discontinuing From Study Therapy Due to ≥1 Drug-related AE
Description
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.
Time Frame
Up to 20 weeks
Title
Number of Participants With ≥1 Drug-related AE Through Week 36
Description
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.
Time Frame
Up to 36 weeks
Title
Number of Participants With ≥1 Serious Adverse Event (SAE) Through Week 36
Description
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.
Time Frame
Up to 36 weeks
Title
Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 36
Description
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').
Time Frame
Up to 36 weeks
Title
Number of Participants With ≥1 Drug-related SAE Through Week 36
Description
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.
Time Frame
Up to 36 weeks
Title
Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 36
Description
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).
Time Frame
Up to 36 weeks
Title
Number of Participants With an AE Resulting in Death Through Week 36
Description
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.
Time Frame
Up to 36 weeks
Secondary Outcome Measure Information:
Title
Area Under the Plasma Concentration-time Curve From Dosing to 672 Hours Postdose (AUC0-672) of Plasma ISL
Description
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.
Time Frame
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.
Title
Maximum Plasma Concentration (Cmax) of ISL
Description
The Cmax of ISL after dosing on Day 1 and Day 140 is reported. Only ISL-treated participants are included in the PK analysis.
Time Frame
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.
Title
Trough Plasma Concentration (Ctrough) of ISL
Description
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.
Time Frame
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.
Title
Apparent Plasma Terminal Half-life (t1/2) of ISL
Description
The plasma t1/2 of ISL after dosing on Day 140 is reported. Only ISL-treated participants are included in the PK analysis.
Time Frame
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.
Title
Number of Participants With ≥1 AE Through Week 24
Description
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.
Time Frame
Up to 24 weeks
Title
Number of Participants With ≥1 Drug-related AE Through Week 24
Description
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.
Time Frame
Up to 24 weeks
Title
Number of Participants With ≥1 SAE Through Week 24
Description
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.
Time Frame
Up to 24 weeks
Title
Number of Participants With a ≥1 Grade 3 to Grade 5 AE up to Week 24
Description
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').
Time Frame
Up to 24 weeks
Title
Number of Participants With ≥1 Drug-related SAE Through Week 24
Description
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.
Time Frame
Up to 24 weeks
Title
Number of Participants With ≥1 Drug-related Grade 3 to 5 AE Through Week 24
Description
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).
Time Frame
Up to 24 weeks
Title
Number of Participants With an AE Resulting in Death Through Week 24
Description
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.
Time Frame
Up to 24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Research Centers of America, LLC ( Site 0007)
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33024
Country
United States
Facility Name
Johns Hopkins School of Medicine - Drug Development Unit ( Site 0002)
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Celerion, Inc. ( Site 0006)
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68502
Country
United States
Facility Name
Magee Womens Research Institute ( Site 0001)
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Hadassah Ein Karem Jerusalem ( Site 0016)
City
Jerusalem
State/Province
Yerushalayim
ZIP/Postal Code
9112001
Country
Israel
Facility Name
Rambam Medical Center ( Site 0017)
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
JOSHA Research ( Site 0015)
City
Bloemfontein
State/Province
Free State
ZIP/Postal Code
9301
Country
South Africa
Facility Name
Clinical HIV Research Unit CHRU ( Site 0014)
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2092
Country
South Africa
Facility Name
Emavundleni Vaccine Centre ( Site 0011)
City
Cape Town
State/Province
Western Cape
ZIP/Postal Code
7750
Country
South Africa
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
33540481
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.
Results Reference
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Learn more about this trial
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)
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