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)

• ClinicalTrials.gov Identifier: NCT04003103
• Recruitment Status: Active, not recruiting
• First Posted: July 1, 2019
• Last Update Posted: December 10, 2020
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

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

Condition or disease	Intervention/treatment	Phase
HIV-1 Infection	Drug: Islatravir; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 250 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: September 19, 2019
• Estimated Primary Completion Date: March 15, 2022
• Estimated Study Completion Date: March 15, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Islatravir 60 mg; 60 mg islatravir + placebo for islatravir administered once monthly, orally in capsule form for 24 weeks	Drug: Islatravir; Islatravir administered orally in capsule form swallowed whole once monthly for 24 weeks; Other Name: MK-8591; Drug: Placebo; Placebo for islatravir administered orally in capsule form swallowed whole once monthly for 24 weeks
Experimental: Islatravir 120 mg; 120 mg islatravir administered once monthly, orally in capsule form for 24 weeks	Drug: Islatravir; Islatravir administered orally in capsule form swallowed whole once monthly for 24 weeks; Other Name: MK-8591
Placebo Comparator: Placebo; Placebo for islatravir administered once monthly, orally in capsule form for 24 weeks	Drug: Placebo; Placebo for islatravir administered orally in capsule form swallowed whole once monthly for 24 weeks

Outcome Measures

Primary Outcome Measures :

1. Participants with an adverse event [ Time Frame: Up to Week 68 ]
   Percentage of participants with at least 1 adverse event (AE)
2. Participants who discontinued from study therapy [ Time Frame: Up to week 20 ]
   Percentage of participants who discontinued from study therapy due to an AE
3. Participants with a drug-related AE [ Time Frame: Up to Week 68 ]
   Percentage of participants with at least 1 drug-related AE
4. Participants with a serious adverse event [ Time Frame: Up to Week 68 ]
   Percentage of participants with at least 1 serious AE (SAE)
5. Participants with a Grade 3 to 5 AE [ Time Frame: Up to Week 68 ]
   Percentage of participants with at least 1 Grade 3 (severe AE) to 5 (death) AE
6. Participants with a serious and drug-related AE [ Time Frame: Up to Week 68 ]
   Percentage of participants with at least 1 AE which is both serious and drug-related
7. Participants with a Grade 3 to 5 and drug-related AE [ Time Frame: Up to Week 68 ]
   Percentage of participants with at least 1 AE which is both Grade 3 (severe AE) to 5 (death) AE and drug-related
8. Participants with an AE resulting in death [ Time Frame: Up to Week 68 ]
   Percentage of participants with an AE which results in death

Secondary Outcome Measures :

1. Area under the concentration-time curve of plasma islatravir [ 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. ]
   Area under the concentration-time curve (AUC) from time 0 to 672 hours post-dose of plasma islatravir
2. Maximum concentration of plasma islatravir [ 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. ]
   Maximum concentration (Cmax) post-dose of plasma islatravir
3. Trough concentration of plasma islatravir [ 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. ]
   Trough concentration (Ctrough) post-dose of plasma islatravir
4. Apparent terminal half-life of plasma islatravir [ 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. ]
   Apparent terminal half-life (t1/2) post-dose of plasma islatravir
5. Participants with an AE up to week 24 [ Time Frame: Up to week 24 ]
   Percentage of participants with at least 1 AE up to week 24
6. Participants with a drug-related AE up to week 24 [ Time Frame: Up to week 24 ]
   Percentage of participants with at least 1 drug-related AE up to week 24
7. Participants with a SAE up to week 24 [ Time Frame: Up to week 24 ]
   Percentage of participants with at least 1 SAE up to week 24
8. Participants with Grade 3 to 5 AE up to week 24 [ Time Frame: Up to week 24 ]
   Percentage of participants with at least 1 Grade 3 to 5 AE up to week 24
9. Participants with a serious and drug-related AE up to week 24 [ Time Frame: Up to week 24 ]
   Percentage of participants with at least 1 serious and drug-related AE up to week 24
10. Participants with Grade 3 to 5 and drug-related AE up to week 24 [ Time Frame: Up to week 24 ]
    Percentage of participants with at least 1 Grade 3 to 5 and drug-related AE up to week 24
11. Participants with an AE resulting in death up to week 24 [ Time Frame: Up to week 24 ]
    Percentage of participants with at least 1 AE resulting in death up to week 24

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

United States, Florida

Research Centers of America, LLC ( Site 0007)

Hollywood, Florida, United States, 33024

United States, Maryland

Johns Hopkins School of Medicine - Drug Development Unit ( Site 0002)

Baltimore, Maryland, United States, 21287

United States, Nebraska

Celerion, Inc. ( Site 0006)

Lincoln, Nebraska, United States, 68502

United States, Pennsylvania

Magee Womens Research Institute ( Site 0001)

Pittsburgh, Pennsylvania, United States, 15213

Israel

Hadassah Ein Karem Jerusalem ( Site 0016)

Jerusalem, Yerushalayim, Israel, 9112001

Rambam Medical Center ( Site 0017)

Haifa, Israel, 3109601

South Africa

JOSHA Research ( Site 0015)

Bloemfontein, Free State, South Africa, 9301

Clinical HIV Research Unit CHRU ( Site 0014)

Johannesburg, Gauteng, South Africa, 2092

Emavundleni Vaccine Centre ( Site 0011)

Cape Town, Western Cape, South Africa, 7750

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT04003103
• Other Study ID Numbers: 8591-016; Merck Protocol Number ( Other Identifier: MK-8591-016 )
• First Posted: July 1, 2019
• Last Update Posted: December 10, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Infection; Communicable Diseases; 4'-ethynyl-2-fluoro-2'-deoxyadenosine; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents