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    Clinical Trial Results:
    A Phase 1b Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of ACE-1334 Plus Standard of Care in Participants with Systemic Sclerosis

    Summary
    EudraCT number
    		 2021-001004-15
    Trial protocol
    		 IT  
    Global end of trial date
    18 Oct 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Oct 2024
    First version publication date
    23 Oct 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MK-2225-002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04948554
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme LLC
    Sponsor organisation address
    126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    18 Oct 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 Oct 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Oct 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The purpose of the MK-2225-002 (A1334-02) study is to evaluate the safety and tolerability of MK-2225 (ACE-1334) plus standard of care (SOC) in participants with Systemic Sclerosis (SSc) following multiple doses.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Mar 2023
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    United States: 3
    Worldwide total number of subjects
    5
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    5
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study enrolled male and female participants at least 18 years of age.

    Pre-assignment
    Screening details
    		 A total of 5 participants were randomized in this study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MK-2225
    Arm description
    		 Participants received MK-2225 plus standard of care (SOC) for 12 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MK-2225
    Investigational medicinal product code
    Other name
    ACE-1334
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered subcutaneously (SC) for 12 weeks

    Arm title
    		 Placebo
    Arm description
    		 Participants received placebo plus SOC for 12 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo administered SC for 12 weeks

    Number of subjects in period 1
    		MK-2225 Placebo
    Started
    4
    1
    Completed
    3
    0
    Not completed
    1
    1
         Adverse event, non-fatal
    -
    1
         site closure
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MK-2225
    Reporting group description
    		 Participants received MK-2225 plus standard of care (SOC) for 12 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo plus SOC for 12 weeks.

    Reporting group values
    		 MK-2225 Placebo Total
    Number of subjects
    		 4 1 5
    Age Categorical
    Units: Participants
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 4 1 5
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Gender Categorical
    Units: Participants
        Female
    		 4 1 5
        Male
    		 0 0 0
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 1 1 2
        Not Hispanic or Latino
    		 3 0 3
    Race
    Units: Subjects
        Black or African American
    		 1 0 1
        Other
    		 1 0 1
        White
    		 2 1 3

    End points

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    End points reporting groups
    Reporting group title
    MK-2225
    Reporting group description
    		 Participants received MK-2225 plus standard of care (SOC) for 12 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo plus SOC for 12 weeks.

    Subject analysis set title
    MK-2225 or Placebo
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received MK-2225 or Placebo.

    Primary: Number of Participants Discontinuing from Study Therapy Due to AE

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    End point title
    		 Number of Participants Discontinuing from Study Therapy Due to AE [1]
    End point description
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE is reported. Study participants who received at least one dose of study treatment were analyzed.
    End point type
    Primary
    End point timeframe
    Up to 12 Weeks
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No between-group statistical analyses were performed for this endpoint, because the study ended early with only 5 participants enrolled.
    End point values
    		 MK-2225 or Placebo
    Number of subjects analysed
    5
    Units: Number of Participants
    1
    No statistical analyses for this end point

    Primary: Number of Participants with ≥1 Adverse Event (AE)

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    End point title
    		 Number of Participants with ≥1 Adverse Event (AE) [2]
    End point description
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE is reported. Study participants who received at least one dose of study treatment were analyzed.
    End point type
    Primary
    End point timeframe
    Up to 20 Weeks
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No between-group statistical analyses were performed for this endpoint, because the study ended early with only 5 participants enrolled.
    End point values
    		 MK-2225 or Placebo
    Number of subjects analysed
    5
    Units: Number of Participants
    5
    No statistical analyses for this end point

    Secondary: Area Under the Concentration-Time Curve (AUC0-tau) of MK-2225

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    End point title
    		 Area Under the Concentration-Time Curve (AUC0-tau) of MK-2225
    End point description
    AUC0-tau is the area under the concentration-time curve for one dose cycle of 14 days (336 hours). Blood samples were collected at designated timepoints to determine AUC0-tau of MK-2225. The analysis population included the participants who completed the study without dosing anomalies.
    End point type
    Secondary
    End point timeframe
    Up to 12 Weeks
    End point values
    		 MK-2225 or Placebo
    Number of subjects analysed
    3 [3]
    Units: hr*ug/mL
        geometric mean (confidence interval 95%)
    585 (398 to 860)
    Notes
    [3] - Analysis population included the 3 participants who completed the study without dosing anomalies.
    No statistical analyses for this end point

    Secondary: Serum Apparent Terminal Half-Life (t1/2) of MK-2225

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    End point title
    		 Serum Apparent Terminal Half-Life (t1/2) of MK-2225
    End point description
    t1/2 is the time required for 50% of drug to be cleared from serum. A value of 9999 indicates t1/2 could not be calculated, due to the insufficient availability of data beyond post Tmax time points.
    End point type
    Secondary
    End point timeframe
    Up to 12 Weeks
    End point values
    		 MK-2225 or Placebo
    Number of subjects analysed
    3 [4]
    Units: hr
        geometric mean (confidence interval 95%)
    9999 (9999 to 9999)
    Notes
    [4] - t1/2 could not be calculated, due to insufficient availability of data beyond post Tmax time points.
    No statistical analyses for this end point

    Secondary: Time to peak Serum Concentration (Tmax) of MK-2225

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    End point title
    		 Time to peak Serum Concentration (Tmax) of MK-2225
    End point description
    Tmax is the amount of time required to reach Cmax. Blood samples were collected at designated timepoints to determine Tmax of MK-2225. The analysis population included the participants who completed the study without dosing anomalies.
    End point type
    Secondary
    End point timeframe
    Up to 12 Weeks
    End point values
    		 MK-2225 or Placebo
    Number of subjects analysed
    3 [5]
    Units: hr
        geometric mean (confidence interval 95%)
    161.82 (115.50 to 167.20)
    Notes
    [5] - Analysis population included the 3 participants who completed the study without dosing anomalies.
    No statistical analyses for this end point

    Secondary: Accumulation Ratio for AUC0-tau (RAUC) of MK-2225

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    End point title
    		 Accumulation Ratio for AUC0-tau (RAUC) of MK-2225
    End point description
    RAUC is the accumulation ratio of AUC0-336 from time 0 to 336 hours. The accumulation ratio (Day 57: Day 1) for AUC0-336 is presented. The analysis population included the participants who completed the study without dosing anomalies.
    End point type
    Secondary
    End point timeframe
    Up to 12 Weeks
    End point values
    		 MK-2225 or Placebo
    Number of subjects analysed
    3 [6]
    Units: hr*ug/mL
        geometric mean (confidence interval 95%)
    2.61 (1.77 to 3.84)
    Notes
    [6] - Analysis population included the 3 participants who completed the study without dosing anomalies.
    No statistical analyses for this end point

    Secondary: Serum Maximum Concentration (Cmax) of MK-2225

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    End point title
    		 Serum Maximum Concentration (Cmax) of MK-2225
    End point description
    Cmax is the maximum concentration of the drug observed in plasma. Blood samples were collected at designated timepoints to determine Cmax of MK-2225. The analysis population included the participants who completed the study without dosing anomalies.
    End point type
    Secondary
    End point timeframe
    Up to 12 Weeks
    End point values
    		 MK-2225 or Placebo
    Number of subjects analysed
    3 [7]
    Units: ug/mL
        geometric mean (confidence interval 95%)
    2.08 (1.29 to 3.37)
    Notes
    [7] - Analysis population included the 3 participants who completed the study without dosing anomalies.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 20 Weeks
    Adverse event reporting additional description
    The analysis population for deaths (all-causes) included all randomized participants. The analysis population for AEs included all randomized participants who received at least one dose of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    MK-2225 or Placebo
    Reporting group description
    		 Participants received MK-2225 or Placebo plus SOC for 12 weeks.

    Serious adverse events
    		 MK-2225 or Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 5 (0.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 MK-2225 or Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 5 (100.00%)
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Blood urine present
         subjects affected / exposed
    2 / 5 (40.00%)
         occurrences all number
    2
    Occult blood positive
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Injury, poisoning and procedural complications
    Post procedural erythema
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    3
    General disorders and administration site conditions
    Injection site erythema
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    2
    Injection site swelling
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Injection site pain
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    6
    Reproductive system and breast disorders
    Genital ulceration
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Polymenorrhoea
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Interstitial lung disease
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Keloid scar
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Neck pain
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Infections and infestations
    COVID-19
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Infected skin ulcer
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1
    Metabolism and nutrition disorders
    Vitamin D deficiency
         subjects affected / exposed
    1 / 5 (20.00%)
         occurrences all number
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 Jun 2021
    Amendment 01: Primary reason for amendment was to incorporate revisions to objectives, endpoints, exclusion criteria, and schedule of assessments.
    10 Sep 2021
    Amendment 02: Primary reason for amendment was to incorporate revisions to objectives and endpoints.
    07 Feb 2022
    Amendment 03: Primary reason for amendment was to incorporate revisions to schedule of assessments.
    24 Aug 2022
    Amendment 04: Primary reason for amendment was to incorporate revisions to study design and objectives.
    20 Sep 2022
    Amendment 05: Primary reason for amendment was to incorporate revisions to exclusion criteria and clinical laboratory assessments.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    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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