MK-8591B (islatravir + ulonivirine)

Associated long-acting platforms

Oral solid form

Administration route

Oral

Therapeutic area(s)

Use case(s)

Use of drug

Dosage

Drug information

Delivery device(s)

No delivery device

Scale-up prospects

Not provided

Tentative equipment list for manufacturing

Not provided

Manufacturing

Not provided

Specific analytical instrument required for characterization of formulation

Not provided

8591-013

Identifier

NCT04564547

Link

https://clinicaltrials.gov/study/NCT04564547

Phase

Phase II

Status

Completed

Sponsor

Merck Sharp & Dohme LLC

More details

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.

Purpose

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

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2021-03-09

Anticipated Date of Last Follow-up
2025-02-10

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2025-01-30

Actual Completion Date
2025-01-30

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: * Is HIV-1 positive with plasma HIV-1 RNA \<50 copies/mL at screening * Has been virologically suppressed on 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 participant 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 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: *

Health status

Study type

Interventional (clinical trial)

Enrollment

161

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Triple-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

8591B-060

Identifier

NCT06891066

Link

https://clinicaltrials.gov/study/NCT06891066

Phase

Phase II

Status

Recruiting

Sponsor

Merck Sharp & Dohme LLC

More details

Investigators are trying to find better treatments for people with HIV-1. In this clinical study, investigators want to see how well a new treatment called ISL+ULO, taken once a week, works compared to an existing treatment called BIC/FTC/TAF, which is taken every day. Investigators will check how many people still have a high level of the virus in their blood after 24 weeks. The investigators also want to understand if the new treatment, MK-8591B, is safe and how well people can handle it.

Purpose

A Study of Islatravir (ISL) and Ulonivirine (ULO) Once Weekly (QW) in Virologically Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) (MK-8591B-060)

Interventions

Intervention 1

Intervention 2

Intervention 3

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2025-04-14

Anticipated Date of Last Follow-up
2025-05-10

Estimated Primary Completion Date
2027-09-24

Estimated Completion Date
2027-09-24

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion: The main inclusion criteria include but are not limited to the following: - Has been receiving Bictegravir/Emtricitabine/Tenofovir alafenamide (BIC/FTC/TAF) therapy with documented viral suppression \[Human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) \<50 copies/mL\] for ≥6 months prior to providing documented informed consent and has no history of prior virologic treatment failure on any past or current regimen. Exclusion: The main exclusion criteria include but are not limited to the following: * Has Human immunodeficiency virus type 2 (HIV-2) infection. * Has a diagnosis of an active Acquired immune deficiency syndrome (AIDS)-defining opportunistic infection. * Has active hepatitis C virus (HCV) coinfection. * Has hepatitis B virus (HBV) coinfection. * H

Health status

Study type

Interventional (clinical trial)

Enrollment

150

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

Proprietary excipients used

Not provided

Novel excipients or existing excipients at a concentration above Inactive Ingredients Database (IID) for the specified route of administration

Not provided

Residual solvents used

Not provided

There are either no relevant patents or these were not yet submitted to LAPaL

Publications

Matthews RP, Patel M, Liu W, Liu Y, Rondón JC, Vargo RC, Stoch SA, Iwamoto M.2025.

Pharmacokinetics of islatravir in participants with moderate hepatic impairment.

Antimicrob Agents Chemother69:e01553-24.https://doi.org/10.1128/aac.01553-24

Islatravir (ISL) is a nucleoside reverse transcriptase translocation inhibitor in development for the treatment of HIV-1 infection. People living with HIV are at risk of liver disease. ISL is metabolized by adenosine deaminase (ADA), which is expressed in the liver; thus, ISL pharmacokinetics (PK) may be affected by hepatic impairment. This study evaluated the effect of moderate hepatic impairment on ISL PK. This nonrandomized, open-label, phase 1 study (MK-8591-030) evaluated the effects of a single oral dose of ISL 60 mg in HIV-seronegative adults with moderate hepatic insufficiency (n = 6) and matched healthy adult participants (n = 6). Blood samples for plasma ISL and 4′-ethynyl-2-fluoro-2′deoxyinosine (M4) and peripheral blood mononuclear cell (PBMC) ISL-triphosphate (ISL-TP) were collected at multiple time points through 672 h, and safety was monitored throughout. Modest decreases in maximum measured concentration (Cmax) and area under the concentration-time curve (AUC) of plasma ISL and AUC of PBMC ISL-TP were observed in participants with moderate hepatic impairment versus matched healthy participants, while ISL-TP Cmax was relatively unchanged. In contrast, plasma M4 was modestly increased in the moderate hepatic impairment group, suggesting that hepatic impairment may result in increased metabolism of ISL to M4 via ADA. The clinical relevance of the overall modest changes in M4, ISL, and ISL-TP levels with moderate hepatic impairment will be contextualized once exposure response data from ongoing clinical studies are available to elucidate the thresholds for clinical efficiency. A single oral dose of ISL 60 mg was generally well tolerated in both groups.

Additional documents

• A clinical study of islatravir and MK-8507 for people with HIV-1 (MK-8591-013) - Protocol Plain Language Summary

Useful links

There are no additional links

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