Dose Ranging, Switch Study of ISL and MK‑8507 Once-Weekly

2024-511041-19-00 Protocol MK-8591-013 Therapeutic exploratory (Phase II) Ended

Start 6 Apr 2021 · End 30 Jan 2025 · Status Ended · 1 EU/EEA countries · 3 sites · Protocol MK-8591-013

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ended
Participants planned 161
Countries 1
Sites 3

HIV-1 Infection

To evaluate the safety and tolerability of ISL + MK-8507 once-weekly as assessed by review of the accumulated safety data.

Key facts

Sponsor
Merck Sharp & Dohme LLC
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Virus Diseases [C02]
Trial duration
6 Apr 2021 → 30 Jan 2025
Decision date (initial)
2024-04-17
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Merck Sharp & Dohme LLC

External identifiers

EU CT number
2024-511041-19-00
EudraCT number
2020-003071-18
WHO UTN
U1111-1302-9886
ClinicalTrials.gov
NCT04564547

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy, Pharmacokinetic, Safety

To evaluate the safety and tolerability of ISL + MK-8507 once-weekly as assessed by review of the accumulated safety data.

Secondary objectives 1

  1. NA

Conditions and MedDRA coding

HIV-1 Infection

VersionLevelCodeTermSystem organ class
20.1 LLT 10068341 HIV-1 infection 10021881

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

  1. Is HIV-1 positive with plasma HIV-1 RNA <50 copies/mL at screening
  2. Has been virologically suppressed on BIC/FTC/TAF for ≥6 months
  3. Has a screening CD4+ T-cell count >200 cells/mm^3 (completed by the central laboratory)
  4. Is male or female, at least 18 years of age, at the time of signing the informed consent
  5. Female participants are eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: a) is not a woman of childbearing potential (WOCBP), or b) 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 10

  1. Has HIV-2 infection
  2. Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
  3. 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)
  4. Has a current (active) diagnosis of acute hepatitis due to any cause
  5. 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
  6. 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
  7. Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies
  8. 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
  9. Has a documented or known virological resistance to ulonivirine or nucleoside/nucleotide reverse transcriptase inhibitors (NNRTI)
  10. Is female and expecting to conceive or donate eggs at any time during the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

  1. Percentage of participants with ≥1 adverse event (AE)
  2. Percentage of participants discontinuing study intervention due to AE

Secondary endpoints 1

  1. NA

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

ulonivirine

PRD987479 · Product

Active substance
Ulonivirine
Substance synonyms
3-CHLORO-5-{[6-OXO-1-{[6-OXO-5-(TRIFLUOROMETHYL)-1,6-DIHYDROPYRIDAZIN-3-YL]METHYL}-4-(TRIFLUOROMETHYL)-1,6-DIHYDROPYRIMIDIN-5-YL]OXY}BENZONITRILE, MK-8507
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
400 mg milligram(s)
Max total dose
57600 mg milligram(s)
Max treatment duration
144 Week(s)
Authorisation status
Not Authorised
MA holder
MERCK & CO. INC.
Paediatric formulation
No
Orphan designation
No

islatravir

PRD9392193 · Product

Active substance
Islatravir
Substance synonyms
4'-ETHYNYL-2-FLUORO-2'-DEOXYADENOSINE, 2'-DEOXY-4'-C-ETHYNYL-2-FLUOROADENOSINE, MK-8591
Pharmaceutical form
CAPSULE
Route of administration
ORAL
Max daily dose
20 mg milligram(s)
Max total dose
2880 mg milligram(s)
Max treatment duration
144 Week(s)
Authorisation status
Not Authorised
MA holder
MERCK & CO. INC.
Paediatric formulation
No
Orphan designation
No

Emtricitabine

SCP31283932 · ATC

Active substance
Emtricitabine
Route of administration
ORAL
Max daily dose
275 mg milligram(s)
Max total dose
184800 mg milligram(s)
Max treatment duration
96 Week(s)
Authorisation status
Authorised
ATC code
J05AR20 — EMTRICITABINE, TENOFOVIR ALAFENAMIDE AND BICTEGRAVIR
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 3

Placebo to ISL

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Placebo to MK-8507

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Placebo to BIC/FTC/TAF

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

290 Total trials 92 Recruiting 184 Ended
Commercial
Sponsor organisation
Merck Sharp & Dohme LLC
Address
126 East Lincoln Avenue, P. O. Box 2000 P. O. Box 2000
City
Rahway
Postcode
07065-4607
Country
United States

Scientific contact point

Organisation
Merck Sharp & Dohme LLC
Contact name
Wayne Greaves

Public contact point

Organisation
Merck Sharp & Dohme LLC
Contact name
Wayne Greaves

Third parties 1

OrganisationCity, countryDuties
PPD Global Central Labs
ORG-100046496
 Zaventem, Belgium Laboratory analysis

Locations

1 EU/EEA country · 3 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ended 48 3
Rest of world
United States, Switzerland
 — 113 —

Investigational sites

France

3 sites · Ended
Centre Hospitalier Universitaire D Orleans
Service des Maladies Infectieuses et Tropicales, 1 Rue Porte Madeleine, Cs 52439, Orleans Cedex 1
Hopital Saint Antoine
Service des Maladies Infectieuses et Tropicales, 184 Rue Du Faubourg Saint Antoine, 75571, Paris Cedex 12
Hopital Saint Louis
Service des Maladies Infectieuses et Tropicales, 1 Avenue Claude Vellefaux, 75010, Paris

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2021-04-06 2025-01-28 2021-04-12 2021-07-16

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

TitleSubmission dateStatusType
Summary of results_2024-511041-19-00_for pub
SUM-115222
 2026-01-16T18:26:33 Submitted Summary of Results

Layperson summary Annex V

TitleSubmission dateStatusType
RPLS_2024-511041-19_for pub 2025-12-23T18:01:53 Submitted Laypersons Summary of Results

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Laypersons summary of results (for publication) RPLS_2024-511041-19_for pub 01DEC2025
Laypersons summary of results (for publication) RPLS_2024-511041-19_FRA_FR_for pub 01DEC2025
Protocol (for publication) D1_Protocol_2024-511041-19_for pub 04R
Recruitment arrangements (for publication) K1_Recruitment Arrangements and IC Procedure_FRA_EN_SM01_for pub 22APR2024
Recruitment arrangements (for publication) K2_Recruitment Doc Brochure_FRA_FR_for pub 1.0
Recruitment arrangements (for publication) K2_Recruitment Doc Material Description_FRA_FR_for pub 1.0
Recruitment arrangements (for publication) K2_Recruitment Doc Patient Female Flyer_FRA_FR_for pub 1.0
Recruitment arrangements (for publication) K2_Recruitment Doc Patient Flyer_FRA_FR_for pub 1.0
Recruitment arrangements (for publication) K2_Recruitment Doc Poster_FRA_FR_for pub 1.0
Subject information and informed consent form (for publication) L1_ICF_FBR consent_FRA_FR_for pub 00R
Subject information and informed consent form (for publication) L1_ICF_Main addendum_FRA_FR_for pub 2.00
Subject information and informed consent form (for publication) L1_ICF_Main consent_FRA_FR_for pub 1.00R
Subject information and informed consent form (for publication) L1_ICF_Optional_addendum smartphone_FRA_FR_for pub 00
Subject information and informed consent form (for publication) L1_ICF_Optional_addendum Tasso_FRA_FR_for pub 00R
Subject information and informed consent form (for publication) L1_ICF_Optional_nursing_FRA_FR_for pub 00
Subject information and informed consent form (for publication) L1_ICF_Optional_pregnancy follow-up_FRA_FR_for pub 00R
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Q and RSI_Biktarvy_for pub 30AUG2022
Summary of results (for publication) Summary of results_2024-511041-19-00_for pub 08JAN2026
Synopsis of the protocol (for publication) D1_PPLS_2024-511041-19_EN_SM01_for pub 1.0
Synopsis of the protocol (for publication) D1_PPLS_2024-511041-19_FRA_FR_SM01_for pub 1.0
Synopsis of the protocol (for publication) D1_Protocol Scientific Synopsis_FRA_FR_for pub v5.0

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-03-15 France Acceptable
2024-04-10
 2024-04-17
2 SUBSTANTIAL MODIFICATION SM-1 2024-11-15 France Acceptable
2025-01-22
 2025-01-29

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