Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017))

• ClinicalTrials.gov Identifier: NCT04223778
• Recruitment Status: Active, not recruiting
• First Posted: January 10, 2020
• Last Update Posted: August 25, 2020
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Tracking Information

• First Submitted Date: January 8, 2020
• First Posted Date: January 10, 2020
• Last Update Posted Date: August 25, 2020
• Actual Study Start Date: February 18, 2020
• Estimated Primary Completion Date: October 15, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 8, 2020)

• Participants with HIV-1 RNA ≥50 copies/mL [ Time Frame: Week 48 ]
  Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48
• Participants with one or more adverse events (AEs) up to Week 48 [ Time Frame: Day 1 to Week 48 ]
  Percentage of participants with one or more adverse events (AEs) up to Week 48
• Participants who discontinued study intervention up to Week 48 [ Time Frame: Day 1 to Week 48 ]
  Percentage of participants who discontinued study intervention due to an AE up to Week 48

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 8, 2020)

• Participants with HIV-1 RNA <40 or <50 copies/mL [ Time Frame: Week 48 ]
  Percentage of participants with HIV-1 RNA <40 or <50 copies/mL at Week 48
• Participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL or <50 copies/mL [ Time Frame: Weeks 48 to 96 ]
  Percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL or <50 copies/mL from Week 48 to Week 96
• Participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL or <50 copies/mL [ Time Frame: Day 1 to Week 96 ]
  Percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL or <50 copies/mL from Day 1 to Week 96
• Change from baseline in CD4+ T-cell count at Week 48 [ Time Frame: Baseline and Week 48 ]
  Change from baseline in cluster of differentiation 4+ (CD4+) T-cell count at Week 48
• Change from baseline in CD4+ T-cell count at Week 96 [ Time Frame: Baseline and Week 96 ]
  Change from baseline in CD4+ T-cell count at Week 96
• Change from Week 48 in CD4+ T-cell count at Week 96 [ Time Frame: Week 48 and Week 96 ]
  Change from Week 48 in CD4+ T-cell count at Week 96
• Participants with evidence of viral drug resistance-associated substitutions at Week 48 [ Time Frame: Week 48 ]
  Percentage of participants with evidence of viral drug resistance-associated substitutions at Week 48
• Participants with evidence of viral drug resistance-associated substitutions at Week 96 [ Time Frame: Week 96 ]
  Percentage of participants with evidence of viral drug resistance-associated substitutions at Week 96
• Change from baseline in fasting low-density lipoprotein cholesterol and nonhigh- density lipoprotein cholesterol to Week 24 [ Time Frame: Baseline and Week 24 ]
  Change from baseline in fasting low-density lipoprotein cholesterol and non-high- density lipoprotein cholesterol to Week 24
• Change from baseline in fasting low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol to Week 48 [ Time Frame: Baseline and Week 48 ]
  Change from baseline in fasting low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol to Week 48
• Change from baseline in body weight at Week 48 [ Time Frame: Baseline and Week 48 ]
  Change from baseline in body weight at Week 48
• Participants with one or more AEs up to Week 96 [ Time Frame: Day 1 to Week 96 ]
  Percentage of participants with one or more AEs from Day 1 up to Week 96
• Participants who discontinued study intervention up to Week 96 [ Time Frame: Day 1 to Week 96 ]
  Percentage of participants who discontinued study intervention due to an AE from Day 1 up to Week 96
• Participants with one or more AEs from Week 48 up to Week 96 [ Time Frame: Weeks 48 to 96 ]
  Percentage of participants with one or more AEs from Week 48 up to Week 96
• Participants who discontinued study intervention from Week 48 up to Week 96 [ Time Frame: Weeks 48 to 96 ]
  Percentage of participants who discontinued study intervention due to an AE from Week 48 up to Week 96

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017))
• Official Title: A Phase 3 Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Antiretroviral Therapy
• Brief Summary: This study will evaluate the safety and efficacy of a switch to MK-8591A (a fixed dose combination of doravirine and islatravir) in human immunodeficiency virus -1 (HIV-1)-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to MK-8591A will be non-inferior to continued treatment with baseline antiretroviral therapy (ART) as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV Infection

Intervention

Drug: DOR/ISL

A FDC of 100 mg DOR/ 0.75 mg ISL taken in tablet form, orally, once daily

Other Name: MK-8591A

Study Arms

• Experimental: Immediate Switch to DOR/ISL
  Participants receiving continuous antiretroviral therapy (ART) will switch to MK-8591A, a fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 96 weeks
  Intervention: Drug: DOR/ISL
• Active Comparator: Baseline Regimen with Delayed Switch to DOR/ISL
  Participants receiving continuous ART for 48 weeks will switch to MK-8591A, a FDC of 100 mg DOR/0.75 mg ISL for 48 weeks
  Intervention: Drug: DOR/ISL

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: January 8, 2020): 578
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 16, 2022
• Estimated Primary Completion Date: October 15, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Is HIV-1 positive
• Has been receiving continuous, stable oral 2-drug or 3-drug combination (± pharmacokinetic (PK) booster) with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 months prior to signing informed consent and has no history of prior virologic treatment failure on any past or current regimen.
• Female is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP); is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle; a WOCBP 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;

Exclusion Criteria:

• Has HIV-2 infection
• 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, including active Hepatitis B Virus (HBV) co-infection
• Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma
• Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies
• Is currently taking long-acting cabotegravir-rilpivirine
• Is currently participating in or has participated in a clinical study with an investigational compound or device from 45 days prior to Day 1 through the study treatment period
• Has a documented or known virologic resistance to DOR
• Female expects to conceive or donate eggs at any time during the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Chile, Colombia, France, Italy, Japan, New Zealand, Poland, Russian Federation, South Africa, Spain, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT04223778
• Other Study ID Numbers: 8591A-017; 2019-000586-20 ( EudraCT Number ); MK-8591A-017 ( Other Identifier: Merck ); 205165 ( Registry Identifier: JAPIC-CTI )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

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

• Responsible Party: Merck Sharp & Dohme Corp.
• Study Sponsor: Merck Sharp & Dohme Corp.
• Collaborators: Not Provided

Investigators

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

• PRS Account: Merck Sharp & Dohme Corp.
• Verification Date: August 2020