Dose Ranging, Switch Study of Islatravir (MK-8591) and Ulonivirine (MK-8507) Once-Weekly in Virologically-Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) [MK-8591-013]

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: HIV-1 Infection

Treatments: Drug: Islatravir; Drug: Placebo to Ulonivirine; Drug: Placebo to BIC/FTC/TAF; Drug: BIC/FTC/TAF; Drug: Placebo to ISL; Drug: Ulonivirine

Study type: Interventional

Funder types: Industry

Identifiers

NCT04564547

2020-003071-18 (EudraCT Number)

U1111-1302-9886 (Registry Identifier)

8591-013

MK-8591-013 (Other Identifier)

2024-511041-19-00 (Registry Identifier)

Details and patient eligibility

About

This is a randomized, controlled, double-blind, study to evaluate the safety and tolerability of islatravir (ISL) + ulonivirine based on review of the accumulated safety data, in adult participants with human immunodeficiency virus type 1 (HIV-1) who have been virologically suppressed for ≥6 months on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) once-daily.

Full description

Based on laboratory findings of decreased lymphocyte and CD4+ T-cell counts across the islatravir program and as described in protocol amendment 2 (approved 01-Dec-2021), participants in study Part 1 (double-blind treatment period) were unblinded, discontinued all study interventions, and switched to standard of care non-study antiretroviral (ART) therapy. Participants who received ISL + ulonivirine (Groups 1 to 3) may have then entered into an unblinded safety monitoring period and were monitored for ≥6 months. As specified in protocol amendment 2, study Parts 2 and 3 were no longer planned or initiated for any participant.

Enrollment: 161 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Is HIV-1 positive with plasma human immunodeficiency virus type 1 (HIV-1) RNA <50 copies/mL at screening

• Has been virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) for ≥6 months

• Has a screening CD4+ T-cell count >200 cells/mm^3 (completed by the central laboratory)

• Is male or female, at least 18 years of age, at the time of signing the informed consent

• Female participants are eligible to participate if 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 a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis)

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 active hepatitis C virus (HCV) coinfection (defined as detectable HCV RNA) or hepatitis B virus (HBV) coinfection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA] positive)
• Has a current (active) diagnosis of acute 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, in situ cervical cancer, or cutaneous Kaposi's sarcoma
• Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant's participation for the full duration of the study
• Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies
• 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 virological resistance to ulonivirine or nucleoside/nucleotide reverse transcriptase inhibitors (NNRTI)
• Is female and expecting to conceive or donate eggs at any time during the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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161 participants in 4 patient groups

Group 1: ISL 20 mg + Ulonivirine 100 mg

Experimental group

Description:

Participants receive ISL 20 mg + ulonivirine 100 mg once weekly (QW) and placebo to BIC/FTC/TAF once daily (QD). Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.

Treatment:

Drug: Ulonivirine

Drug: Placebo to BIC/FTC/TAF

Drug: Placebo to Ulonivirine

Drug: Islatravir

Group 2: ISL 20 mg + Ulonivirine 200 mg

Experimental group

Description:

Participants receive ISL 20 mg + ulonivirine 200 mg QW and placebo to BIC/FTC/TAF QD. Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.

Treatment:

Drug: Ulonivirine

Drug: Placebo to BIC/FTC/TAF

Drug: Placebo to Ulonivirine

Drug: Islatravir

Group 3: ISL 20 mg + Ulonivirine 400 mg

Experimental group

Description:

Participants receive ISL 20 mg + ulonivirine 400 mg QW and placebo to BIC/FTC/TAF QD. Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.

Treatment:

Drug: Ulonivirine

Drug: Placebo to BIC/FTC/TAF

Drug: Islatravir

Group 4: BIC/FTC/TAF

Active Comparator group

Description:

Participants receive placebo to ISL + placebo to ulonivirine QW and BIC/FTC/TAF 50 mg/200 mg/25 mg QD.

Treatment:

Drug: Placebo to ISL

Drug: BIC/FTC/TAF

Drug: Placebo to Ulonivirine