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    Summary
    EudraCT Number:2019-000586-20
    Sponsor's Protocol Code Number:MK-8591A-017
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2019-11-28
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2019-000586-20
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    DOR/ISL Open-label Switch
    A.3.2Name or abbreviated title of the trial where available
    DOR/ISL Open-Label Switch
    A.4.1Sponsor's protocol code numberMK-8591A-017
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorMerck Sharp & Dohme LLC.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMerck Sharp & Dohme LLC.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDoravirine/Islatravir
    D.3.2Product code MK-8591A
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDORAVIRINE
    D.3.9.2Current sponsor codeMK-1439
    D.3.9.4EV Substance CodeSUB177834
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMK-8591
    D.3.9.2Current sponsor codeMK-8591
    D.3.9.4EV Substance CodeSUB130009
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.75
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    HIV-1 Infection
    E.1.1.1Medical condition in easily understood language
    HIV-1 Infection
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10068341
    E.1.2Term HIV-1 infection
    E.1.2System Organ Class 100000004862
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    1. To evaluate the antiretroviral activity following switch to Doravirine/Islatravir (DOR/ISL) compared to continued baseline antiretroviral therapy (ART) as assessed by the percentage of participants with Human Immunodeficiency Virus 1 (HIV-1) RNA ≥50 copies/mL at Week 48
    2. To evaluate the safety and tolerability of switch to DOR/ISL compared to continued baseline ART as assessed by review of the accumulated safety data through Week 48
    E.2.2Secondary objectives of the trial
    1. To evaluate the antiretroviral activity at Week 48
    2. To evaluate the antiretroviral activity at Week 96
    3. To evaluate the sustained antiretroviral activity in participants who switched to DOR/ISL on Day 1 at Week 96
    4. To evaluate the immunologic effect of switch to DOR/ISL as measured by change from baseline in CD4+ T-cell count at Week 48
    5. To evaluate the immunologic effect of DOR/ISL as assessed by the change from baseline in CD4+ T-cell count at Week 96
    6. To evaluate the development of viral drug resistance
    7. To evaluate the effect on fasting lipid profiles following switch to DOR/ISL compared to continued baseline ART
    8. To evaluate the effect of switch to DOR/ISL compared to continued baseline ART on weight
    9. To evaluate the safety and tolerability of DOR/ISL through Week 96
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Merck will conduct Future Biomedical Research on DNA (Blood) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time.
    E.3Principal inclusion criteria
    1. Is HIV-1 positive with plasma HIV-1 RNA <50 copies/mL at screening
    2. Has been receiving continuous, stable oral 2-drug or 3-drug combination (± 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
    3. Is male or female at least 18 years of age at the time of signing the informed consent
    4. A 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)
    OR
    - Is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 6 weeks, corresponding to the time needed to eliminate any study intervention(s) (eg, 5 terminal half-lives) after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention
    - 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 (eg, 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
    - The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy
    5. The participant provides written informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research
    E.4Principal exclusion criteria
    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 an active diagnosis of hepatitis due to any cause, including active HBV co-infection (defined as HBsAg-positive or HBV DNA positive)
    4. 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
    5. 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, such that it is not in the best interest of the participant to participate
    6. Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies from 45 days prior to Day 1 through the study treatment period
    7. Is currently taking long-acting cabotegravir-rilpivirine
    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 virologic resistance to DOR, as demonstrated by any of the following DOR resistance substitutions in reverse transcriptase:
    V106A/M, V108I, Y188L, H221Y, P225H, F227C/L, M230I/L, L234I, P236L, or Y318F
    10. Has exclusionary laboratory values (completed by the central laboratory) within 45 days prior to Day 1
    11. Is female and expecting to conceive or donate eggs at any time during the study
    E.5 End points
    E.5.1Primary end point(s)
    1. Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48
    2. Percentage of participants with one or more adverse events (AEs) up to Week 48
    3. Percentage of participants who discontinued study intervention due to an AE up to Week 48
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Week 48
    2. Week 48
    3. Week 48
    E.5.2Secondary end point(s)
    1. Percentage of participants with HIV-1 RNA <40 or <50 copies/mL at Week 48
    2. Percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL or <50 copies/mL from Week 48 to Week 96
    3. Percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL or <50 copies/mL from Day 1 to Week 96
    4. Change from baseline in CD4+ T-cell count at Week 48
    5. Change from baseline in CD4+ T-cell count at Week 96
    6. Change from Week 48 in CD4+ T-cell count at Week 96
    7. Percentage of participants with evidence of viral drug resistance associated substitutions at Week 48
    8. Percentage of participants with evidence of viral drug resistance-associated substitutions at Week 96
    9. Change from baseline in fasting low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol to Week 24
    10. Change from baseline in fasting low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol to Week 48
    11. Change from baseline in body weight at Week 48
    12. Percentage of participants with one or more AEs from Day 1 up to Week 96
    13. Percentage of participants who discontinued study intervention due to an AE from Day 1 up to Week 96
    14. Percentage of participants with one or more AEs from Week 48 up to Week 96
    15. Percentage of participants who discontinued study intervention due to an AE from Week 48 up to Week 96
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Week 48
    2. Weeks 48 to 96
    3. Day 1 to Week 96
    4. Baseline and Week 48
    5. Baseline and Week 96
    6. Week 48 and Week 96
    7. Week 48
    8. Week 96
    9. Baseline and Week 24
    10. Baseline and Week 48
    11. Baseline and Week 48
    12. Day 1 to Week 96
    13. Day 1 to Week 96
    14. Weeks 48 to 96
    15. Weeks 48 to 96
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Approved in Poland Antiretroviral Therapy (ART) in the treatment of patient with HIV
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Information not present in EudraCT
    E.8.4 The trial involves multiple sites in the Member State concerned Information not present in EudraCT
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA32
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    Chile
    Colombia
    Japan
    New Zealand
    South Africa
    United States
    France
    Poland
    Spain
    Switzerland
    Italy
    Russian Federation
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 289
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 289
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 169
    F.4.2.2In the whole clinical trial 578
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    At the end of Week 96, provided development of DOR/ISL continues, there will be a mechanism for all eligible participants to continue receiving study intervention without interruption until it becomes commercially accessible. Eligible participants are those who have completed the last scheduled study visit and are considered by the investigator to derive clinical benefit from continued administration of their current regimen
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-03-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-01-13
    P. End of Trial
    P.End of Trial StatusCompleted
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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