Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 3, Multi-Center, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of CK-3773274 in Adults with Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction

    Summary
    EudraCT number
    		 2021-003536-92
    Trial protocol
    		 HU   DK   ES   NL   CZ   PL   PT   IT  
    Global end of trial date
    18 Dec 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Dec 2024
    First version publication date
    28 Dec 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CY 6031
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05186818
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Cytokinetics, Inc.
    Sponsor organisation address
    350 Oyster Point Blvd, South San Francisco, United States, 94080
    Public contact
    Medical Affairs, Cytokinetics, Inc., +1 6506242929, medicalaffairs@cytokinetics.com
    Scientific contact
    Medical Affairs, Cytokinetics, Inc., +1 6506242929, medicalaffairs@cytokinetics.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 Dec 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 Dec 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Dec 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the effect of CK-3773274 on exercise capacity in patients with symptomatic obstructive hypertrophic cardiomyopathy
    Protection of trial subjects
    This study was conducted in accordance with the protocol, consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines, applicable International Council for Harmonisation guidelines for Good Clinical Practices, and all applicable laws and regulations.
    Background therapy
    		 Participants on beta-blockers, verapamil, diltiazem, or disopyramide were to have been on a stable regimen for > 6 weeks prior to randomization, which was individually optimized according to local practice.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Feb 2022
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 7
    Country: Number of subjects enrolled
    Poland: 17
    Country: Number of subjects enrolled
    Portugal: 4
    Country: Number of subjects enrolled
    Spain: 32
    Country: Number of subjects enrolled
    Czechia: 1
    Country: Number of subjects enrolled
    Denmark: 7
    Country: Number of subjects enrolled
    France: 17
    Country: Number of subjects enrolled
    Germany: 11
    Country: Number of subjects enrolled
    Hungary: 7
    Country: Number of subjects enrolled
    Italy: 12
    Country: Number of subjects enrolled
    China: 46
    Country: Number of subjects enrolled
    United States: 94
    Country: Number of subjects enrolled
    United Kingdom: 18
    Country: Number of subjects enrolled
    Israel: 9
    Worldwide total number of subjects
    282
    EEA total number of subjects
    115
    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)
    169
    From 65 to 84 years
    113
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This study included adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM) and was conducted at 82 study centers in China, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Portugal, Spain, the United Kingdom, and the United States.

    Pre-assignment
    Screening details
    		 Participants had: left ventricular (LV) hypertrophy and non-dilated LV chamber in the absence of other cardiac disease, and end diastolic LV wall thickness ≥ 15 mm in ≥ 1 myocardial segment or ≥ 13 mm in ≥ 1 wall segment; a known disease-causing gene mutation or positive family history of HCM; a Valsalva LV outflow tract gradient ≥ 50 mmHg.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Aficamten
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Aficamten
    Investigational medicinal product code
    CK-3773274
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants randomized to aficamten started at a dose of 5 mg once daily. At 2-week intervals, doses could have escalated sequentially to 10, 15, or 20 mg once daily based on echocardiography results. Participants with Valsalva LVOT-G ≥ 30 mmHg and biplane LVEF ≥ 55% could escalate to the next higher dose; if these criteria were not met, the participant remained at their existing dose. The Week 6 visit was the last time a dose could have been escalated; no dose escalations were allowed after this time point. At Week 8 and later, dose reductions (to the next lower dose) occurred if echocardiography results showed that LVEF was < 50%. Overall, participants were to receive aficamten for a total of 24 weeks.

    Arm title
    		 Placebo
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo for aficamten
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants randomized to placebo received new study drug kits on the same schedule as participants randomized to aficamten to maintain the blind during the dose titration phase.

    Number of subjects in period 1
    		Aficamten Placebo
    Started
    142
    140
    Completed
    137
    136
    Not completed
    5
    4
         Consent withdrawn by subject
    2
    -
         Physician decision
    -
    1
         Adverse event, non-fatal
    1
    2
         Transportation issue due to COVID-19
    -
    1
         Protocol deviation
    2
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Aficamten
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group values
    		 Aficamten Placebo Total
    Number of subjects
    		 142 140 282
    Age categorical
    Units: Subjects
        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)
    		 85 84 169
        From 65-84 years
    		 57 56 113
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 59.0 (18 to 83) 60.0 (23 to 84) -
    Gender categorical
    Units: Subjects
        Female
    		 56 59 115
        Male
    		 86 81 167
    pVO2 per CPET
    Units: mL/kg/min
        arithmetic mean (standard deviation)
    		 18.4 ( 4.5 ) 18.6 ( 4.5 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Aficamten
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Primary: Change from Baseline in pVO2 at Week 24

    		 Close Top of page
    End point title
    		 Change from Baseline in pVO2 at Week 24
    End point description
    The effect of aficamten on exercise capacity in participants with symptomatic obstructive HCM was determined through changes in peak oxygen uptake (pVO2) after 24 weeks of treatment. pVO2 was measured by cardiopulmonary exercise testing (CPET; treadmill or bicycle).
    End point type
    Primary
    End point timeframe
    Baseline (ie, start of study drug) through Week 24
    End point values
    		 Aficamten Placebo
    Number of subjects analysed
    142
    140
    Units: mL/kg/min
        least squares mean (standard error)
    1.76 ( 0.25 )
    0.02 ( 0.25 )
    Statistical analysis title
    		 Primary Analysis
    Statistical analysis description
    The primary analysis was performed using an analysis of covariance (ANCOVA) model that included terms of treatment, randomization stratification factors (beta-blocker use status and CPET modality), baseline pVO2 and baseline body weight as covariates in the Full Analysis Set.
    Comparison groups
    Aficamten v Placebo
    Number of subjects included in analysis
    282
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.04
         upper limit
    		 2.44
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.36

    Secondary: Change from Baseline in KCCQ-CSS at Week 24

    		 Close Top of page
    End point title
    		 Change from Baseline in KCCQ-CSS at Week 24
    End point description
    The effect of aficamten on patient health status was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a patient-reported outcome designed to assess the physical limitations, symptoms, self-efficacy, social imitation, and quality of life of patients with heart failure symptoms. The KCCQ-Clinical Symptoms Score (KCCQ-CSS) is scored on a scale from 0 to 100, with higher scores indicating better physical functioning and symptoms.
    End point type
    Secondary
    End point timeframe
    Baseline (ie, initiation of study drug) to Week 24
    End point values
    		 Aficamten Placebo
    Number of subjects analysed
    142
    140
    Units: score on a scale
        least squares mean (standard error)
    11.6 ( 1.0 )
    4.3 ( 1.0 )
    Statistical analysis title
    		 Analysis of Change in KCCQ-CSS at Week 24
    Comparison groups
    Aficamten v Placebo
    Number of subjects included in analysis
    282
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS mean difference
    Point estimate
    7.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.6
         upper limit
    		 10.1
    Variability estimate
    Standard deviation
    Dispersion value
    1.4

    Secondary: Change from Baseline in KCCQ-CSS at Week 12

    		 Close Top of page
    End point title
    		 Change from Baseline in KCCQ-CSS at Week 12
    End point description
    The effect of aficamten on patient health status was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a patient-reported outcome designed to assess the physical limitations, symptoms, self-efficacy, social limitation, and quality of life of patients with heart failure symptoms. The KCCQ-Clinical Symptoms Score (KCCQ-CSS) is scored on a scale from 0 to 100, with higher scores indicating better physical functioning and symptoms.
    End point type
    Secondary
    End point timeframe
    Baseline (ie, start of study drug) to Week 12
    End point values
    		 Aficamten Placebo
    Number of subjects analysed
    142
    140
    Units: score on a scale
        least squares mean (standard error)
    11.1 ( 0.9 )
    4.0 ( 0.9 )
    Statistical analysis title
    		 Analysis of Change in KCCQ-CSS at Week 12
    Comparison groups
    Aficamten v Placebo
    Number of subjects included in analysis
    282
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS mean difference
    Point estimate
    7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.5
         upper limit
    		 9.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.3

    Secondary: Proportion of Participants with ≥1 Class Improvement in NYHA Functional Class from Baseline to Week 24

    		 Close Top of page
    End point title
    		 Proportion of Participants with ≥1 Class Improvement in NYHA Functional Class from Baseline to Week 24
    End point description
    The effect of aficamten on New York Heart Association (NYHA) functional classification was evaluated through changes observed from baseline through 24 weeks of treatment.
    End point type
    Secondary
    End point timeframe
    Baseline (ie, start of study drug) to Week 24
    End point values
    		 Aficamten Placebo
    Number of subjects analysed
    142
    140
    Units: % of participants
        number (not applicable)
    58.5
    24.3
    Statistical analysis title
    		 Analysis 1: NYHA ≥1 Class Improvement at Week 24
    Comparison groups
    Aficamten v Placebo
    Number of subjects included in analysis
    282
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Rate difference
    Point estimate
    34.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 23.4
         upper limit
    		 45
    Statistical analysis title
    		 Analysis 2: NYHA ≥1 Class Improvement at Week 24
    Comparison groups
    Aficamten v Placebo
    Number of subjects included in analysis
    282
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    4.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.6
         upper limit
    		 7.6

    Secondary: Proportion of Participants with ≥1 Class Improvement in NYHA Functional Class from Baseline to Week 12

    		 Close Top of page
    End point title
    		 Proportion of Participants with ≥1 Class Improvement in NYHA Functional Class from Baseline to Week 12
    End point description
    The effect of aficamten on NYHA functional cassification was evaluated through changes observed from baseline through 12 weeks of treatment.
    End point type
    Secondary
    End point timeframe
    Baseline (ie, start of study drug) to Week 12
    End point values
    		 Aficamten Placebo
    Number of subjects analysed
    142
    140
    Units: % of participants
        number (not applicable)
    48.6
    17.9
    Statistical analysis title
    		 Analysis 1: NYHA ≥1 Class Improvement at Week 12
    Comparison groups
    Aficamten v Placebo
    Number of subjects included in analysis
    282
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Rate difference
    Point estimate
    30.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 20.6
         upper limit
    		 41
    Statistical analysis title
    		 Analysis 2: NYHA ≥1 Class Improvement at Week 12
    Comparison groups
    Aficamten v Placebo
    Number of subjects included in analysis
    282
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    4.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.6
         upper limit
    		 8.4

    Secondary: Change From Baseline in Valsalva LVOT-G at Week 24

    		 Close Top of page
    End point title
    		 Change From Baseline in Valsalva LVOT-G at Week 24
    End point description
    The effect of aficamten treatment on Valsalva left ventricular outflow tract gradient (LVOT-G) was evaluated through changes from baseline to Week 24.
    End point type
    Secondary
    End point timeframe
    Baseline (ie, start of study drug) to Week 24
    End point values
    		 Aficamten Placebo
    Number of subjects analysed
    142
    140
    Units: mmHg
        least squares mean (standard error)
    -48 ( 2.4 )
    2 ( 2.4 )
    Statistical analysis title
    		 Analysis of Change in Valsalva LVOT-G at Week 24
    Comparison groups
    Aficamten v Placebo
    Number of subjects included in analysis
    282
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS mean difference
    Point estimate
    -50
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -57
         upper limit
    		 -44
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.4

    Secondary: Change From Baseline in Valsalva LVOT-G at Week 12

    		 Close Top of page
    End point title
    		 Change From Baseline in Valsalva LVOT-G at Week 12
    End point description
    The effect of aficamten treatment on Valsalva LVOT-G was evaluated through changes from baseline to Week 12.
    End point type
    Secondary
    End point timeframe
    Baseline (ie, start of study drug) to Week 12
    End point values
    		 Aficamten Placebo
    Number of subjects analysed
    142
    140
    Units: mmHg
        least squares mean (standard error)
    -46 ( 2.4 )
    3 ( 2.4 )
    Statistical analysis title
    		 Analysis of Change in Valsalva LVOT-G at Week 12
    Comparison groups
    Aficamten v Placebo
    Number of subjects included in analysis
    282
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS mean difference
    Point estimate
    -48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -55
         upper limit
    		 -42
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.4

    Secondary: Proportion of Participants With Valsalva LVOT-G <30 mmHg at Week 24

    		 Close Top of page
    End point title
    		 Proportion of Participants With Valsalva LVOT-G <30 mmHg at Week 24
    End point description
    The effect of aficamten treatment on Valsalva LVOT-G was evaluated through changes from baseline to Week 24.
    End point type
    Secondary
    End point timeframe
    Baseline (ie, start of study drug) to Week 24
    End point values
    		 Aficamten Placebo
    Number of subjects analysed
    142
    140
    Units: % of participants
        number (not applicable)
    49.3
    3.6
    Statistical analysis title
    		 Analysis 1: Valsalva LVOT-G <30 mmHg at Week 24
    Comparison groups
    Aficamten v Placebo
    Number of subjects included in analysis
    282
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Rate difference
    Point estimate
    45.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 36.9
         upper limit
    		 54.4
    Statistical analysis title
    		 Analysis 2: Valsalva LVOT-G <30 mmHg at Week 24
    Comparison groups
    Aficamten v Placebo
    Number of subjects included in analysis
    282
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    25.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.1
         upper limit
    		 88.2

    Secondary: Proportion of Participants With Valsalva LVOT-G <30 mmHg at Week 12

    		 Close Top of page
    End point title
    		 Proportion of Participants With Valsalva LVOT-G <30 mmHg at Week 12
    End point description
    The effect of aficamten treatment on Valsalva LVOT-G was evaluated through changes from baseline to Week 12.
    End point type
    Secondary
    End point timeframe
    Baseline (ie, start of study drug) to Week 12
    End point values
    		 Aficamten Placebo
    Number of subjects analysed
    142
    140
    Units: % of Participants
        number (not applicable)
    52.1
    5.7
    Statistical analysis title
    		 Analysis 1: Valsalva LVOT-G <30 mmHg at Week 12
    Comparison groups
    Aficamten v Placebo
    Number of subjects included in analysis
    282
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Rate difference
    Point estimate
    46.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 37.3
         upper limit
    		 55.5
    Statistical analysis title
    		 Analysis 2: Valsalva LVOT G <30 mmHg at Week 12
    Comparison groups
    Aficamten v Placebo
    Number of subjects included in analysis
    282
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.8
         upper limit
    		 44.4

    Secondary: Duration of SRT Eligibility During the 24-week Treatment Period for Participants Who Were SRT Eligible at Baseline

    		 Close Top of page
    End point title
    		 Duration of SRT Eligibility During the 24-week Treatment Period for Participants Who Were SRT Eligible at Baseline
    End point description
    The effect of aficamten treatment on the duration of eligibility for septal reduction therapy (SRT) was evaluated over the 24-week treatment period.
    End point type
    Secondary
    End point timeframe
    Baseline (ie, start of study drug) to Week 24
    End point values
    		 Aficamten Placebo
    Number of subjects analysed
    32 [1]
    29 [2]
    Units: days
        least squares mean (standard error)
    35.3 ( 7.9 )
    113.4 ( 8.1 )
    Notes
    [1] - 32 of the 142 participants in this arm were SRT eligible at baseline
    [2] - 29 of the 140 participants in this arm were SRT eligible at baseline
    Statistical analysis title
    		 Analysis of duration of SRT eligibility
    Comparison groups
    Aficamten v Placebo
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -78.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -99.8
         upper limit
    		 -56.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    10.9

    Secondary: Change From Baseline to Week 24 in Total Workload During CPET

    		 Close Top of page
    End point title
    		 Change From Baseline to Week 24 in Total Workload During CPET
    End point description
    The effect of aficamten on intensity of exercise (based on speed, incline, participant weight, etc.) during CPET was evaluated. Workload is an indication of the energy expended during cardiopulmonary exercise testing.
    End point type
    Secondary
    End point timeframe
    Baseline (ie, start of study drug) to Week 24
    End point values
    		 Aficamten Placebo
    Number of subjects analysed
    142
    140
    Units: watts
        least squares mean (standard error)
    13.4 ( 2.1 )
    1.2 ( 2.1 )
    Statistical analysis title
    		 Analysis of workload at Week 24
    Comparison groups
    Aficamten v Placebo
    Number of subjects included in analysis
    282
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    12.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.4
         upper limit
    		 18
    Variability estimate
    Standard error of the mean
    Dispersion value
    3

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected from initiation of IP through 4 weeks after the last dose of IP; as such, all serious and non-serious adverse events were treatment-emergent.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Aficamten
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Serious adverse events
    		 Aficamten Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 142 (5.63%)
    13 / 140 (9.29%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute lymphocytic leukaemia
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of the oral cavity
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Radius fracture
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Hypertrophic cardiomyopathy
         subjects affected / exposed
    3 / 142 (2.11%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thalassaemia
         subjects affected / exposed
    1 / 142 (0.70%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 142 (0.70%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia supraventricular
         subjects affected / exposed
    1 / 142 (0.70%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinoatrial block
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Carotid artery stenosis
         subjects affected / exposed
    1 / 142 (0.70%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 142 (0.70%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Microcytic anaemia
         subjects affected / exposed
    1 / 142 (0.70%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 142 (0.70%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
         subjects affected / exposed
    1 / 142 (0.70%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Sepsis
         subjects affected / exposed
    1 / 142 (0.70%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 140 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Aficamten Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    105 / 142 (73.94%)
    96 / 140 (68.57%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    11 / 142 (7.75%)
    3 / 140 (2.14%)
         occurrences all number
    11
    3
    Congenital, familial and genetic disorders
    Hypertrophic cardiomyopathy
         subjects affected / exposed
    3 / 142 (2.11%)
    3 / 140 (2.14%)
         occurrences all number
    3
    3
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    10 / 142 (7.04%)
    4 / 140 (2.86%)
         occurrences all number
    12
    5
    Angina pectoris
         subjects affected / exposed
    3 / 142 (2.11%)
    7 / 140 (5.00%)
         occurrences all number
    4
    12
    Nervous system disorders
    Headache
         subjects affected / exposed
    11 / 142 (7.75%)
    10 / 140 (7.14%)
         occurrences all number
    12
    13
    Dizziness
         subjects affected / exposed
    6 / 142 (4.23%)
    2 / 140 (1.43%)
         occurrences all number
    6
    2
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    3 / 142 (2.11%)
    7 / 140 (5.00%)
         occurrences all number
    3
    9
    Chest pain
         subjects affected / exposed
    6 / 142 (4.23%)
    2 / 140 (1.43%)
         occurrences all number
    13
    2
    Chest discomfort
         subjects affected / exposed
    5 / 142 (3.52%)
    3 / 140 (2.14%)
         occurrences all number
    7
    3
    Asthenia
         subjects affected / exposed
    4 / 142 (2.82%)
    0 / 140 (0.00%)
         occurrences all number
    6
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 142 (0.70%)
    4 / 140 (2.86%)
         occurrences all number
    1
    4
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    6 / 142 (4.23%)
    4 / 140 (2.86%)
         occurrences all number
    6
    4
    Gastrooesophageal reflux disease
         subjects affected / exposed
    4 / 142 (2.82%)
    0 / 140 (0.00%)
         occurrences all number
    4
    0
    Diarrhoea
         subjects affected / exposed
    2 / 142 (1.41%)
    4 / 140 (2.86%)
         occurrences all number
    2
    4
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    8 / 142 (5.63%)
    8 / 140 (5.71%)
         occurrences all number
    8
    8
    Cough
         subjects affected / exposed
    5 / 142 (3.52%)
    1 / 140 (0.71%)
         occurrences all number
    6
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    4 / 142 (2.82%)
    2 / 140 (1.43%)
         occurrences all number
    4
    2
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    9 / 142 (6.34%)
    12 / 140 (8.57%)
         occurrences all number
    13
    16
    COVID-19
         subjects affected / exposed
    8 / 142 (5.63%)
    9 / 140 (6.43%)
         occurrences all number
    8
    11
    Nasopharyngitis
         subjects affected / exposed
    5 / 142 (3.52%)
    6 / 140 (4.29%)
         occurrences all number
    5
    7
    Urinary tract infection
         subjects affected / exposed
    4 / 142 (2.82%)
    1 / 140 (0.71%)
         occurrences all number
    4
    1
    Bronchitis
         subjects affected / exposed
    0 / 142 (0.00%)
    4 / 140 (2.86%)
         occurrences all number
    0
    4

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    31 Mar 2023
    Protocol Amendment 03: Added endpoints to evaluate eligibility for septal reduction therapy and updated pVO2 inclusion criterion. Added option to increase the sample size based on ̉pVO2 variability and missing data rate.

    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.
    The length of the study was relatively short and did not permit assessment of longer-term cardiovascular outcomes. Ethnic diversity was limited.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/38739079
    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.

    European Medicines Agency © 1995-Mon May 05 14:29:18 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA