A Phase 3 interventional study of mavacamten and Placebo in Obstructive Hypertrophic Cardiomyopathy, sponsored by MyoKardia, Inc.. Completed at 71 sites in 13 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-10-04.
Sponsored by MyoKardia, Inc. · Phase 3, Interventional, and Treatment
This is a multicenter, international, double-blind study of the administration of mavacamten in participants with symptomatic obstructive HCM (oHCM). Approximately 220 participants will be randomized to receive placebo or mavacamten.
Key Inclusion Criteria:
Key Exclusion Criteria:
Drug: mavacamten
Drug: Placebo
mavacamten capsules
Also known as: MYK-461
placebo oral capsule
Percentage of Participants Achieving A Clinical Response
A positive clinical response (value="YES") is defined as having achieved either an improvement of at least 1.5 mL/kg/min in peak oxygen consumption (pVO2) as determined by cardiopulmonary exercise testing (CPET) and a reduction of one or more class in New York Heart Association (NYHA) functional classification (e.g.I, II, III, or IV) -OR- an improvement of 3.0 mL/kg/min or more in pVO2 with no worsening in NYHA Functional Class.
Time frame: 30 weeks
Changes From Baseline to Week 30 in Post Exercise in LVOT Peak Gradient.
The post-exercise LVOT gradient was measured from echocardiograms obtained at baseline and week 30 following a study-specified exercise protocol and read by the Cardiovascular Imaging Core Laboratory (CICL, Boston MA). Change from baseline was determined as per the study statistical analysis plan and compared between treatment arms.
Time frame: 30 weeks
Change From Baseline to Week 30 in pVO2 as Assessed by CPET
Cardiopulmonary exercise testing (CPET) was performed at baseline and week 30 following a study-specified protocol and peak oxygen consumption (pVO2) was determined by the Cardiovascular Metabolic Disease Research Institute (CMDRI, Palo Alto, CA). Change from baseline was determined as per the study statistical analysis plan and compared between treatment arms.
Time frame: 30 weeks
Proportion of Participants With at Least 1 Class Improvement in NYHA Functional Class From Baseline to Week 30
New York Heart Association (NYHA) functional classification was determined by the principal investigator at baseline and at specified timepoints in the study. At baseline, all subjects were NYHA Class II or III. For the secondary outcome, NYHA class at Week 30 was compared to baseline and the proportion of subjects with an improvement of at least one class was determined, and the difference between treatment groups was analyzed. The proportion was also multiplied by 100 to provide the result as a percent.
Time frame: 30 weeks
Change From Baseline to Week 30 in Participant-reported Health-related Quality of Life as Assessed by the KCCQ Score
The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a patient reported outcome instrument with minimum score = 0 and maximum score = 100 where higher score indicates better health status. There are no units to the score. The instrument utilizes a recall period of 2 weeks over which patients describe the frequency and severity of their symptoms, their physical and social limitations, and how they perceive their heart failure symptoms to affect their quality of life. The KCCQ clinical summary (KCCQ-CS) score, a prespecified secondary outcome of EXPLORER-HCM, combines the physical limitation and total symptom scores.
Time frame: 30 weeks
Change From Baseline to Week 30 in Participant-reported Severity of HCM Symptoms as Assessed by the HCMSQ Score
The Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ) is a patient reported outcome instrument that is a daily self-administered 11-item questionnaire. The HCMSQ assesses the core symptoms of HCM (tiredness/fatigue, heart palpitations, chest pain, dizziness, and shortness of breath). The Shortness of Breath domain score, a pre-specified secondary outcome of EXPLORER-HCM, assesses the frequency and severity of shortness of breath. The minimum score = 0 and maximum score = 18 where lower score indicates better health status. There are no units to the score.
Time frame: 30 weeks
Subjects who met all of the inclusion criteria and none of the exclusion criteria were enrolled into the study and were randomized 1:1 to receive mavacamten (2.5, 5, 10, or 15 mg capsule) or placebo once daily for 30 weeks, followed by an 8 week post-treatment period. In total, 429 participants were assessed for eligibility and 251 were enrolled from 68 sites in the United States and EMEA.
| Milestone | Mavacamten (MYK-461) | Placebo |
|---|---|---|
| Started | 123 | 128 |
| Completed | 119 | 125 |
| Not completed | 4 | 3 |
| Withdrew: Death | 0 | 1 |
| Withdrew: Did not complete week 30 assessments due to scheduling conflict | 1 | 0 |
| Withdrew: Adverse event | 2 | 0 |
| Withdrew: Withdrawal by subject | 1 | 1 |
| Withdrew: Week 30 not completed due to circumstances surrounding the covid-19 pandemic | 0 | 1 |
A positive clinical response (value="YES") is defined as having achieved either an improvement of at least 1.5 mL/kg/min in peak oxygen consumption (pVO2) as determined by cardiopulmonary exercise testing (CPET) and a reduction of one or more class in New York Heart Association (NYHA) functional classification (e.g.I, II, III, or IV) -OR- an improvement of 3.0 mL/kg/min or more in pVO2 with no worsening in NYHA Functional Class.
| Participants | Mavacamten (MYK-461) | Placebo |
|---|---|---|
| Percentage of Participants Achieving A Clinical Response | 45 | 22 |
The post-exercise LVOT gradient was measured from echocardiograms obtained at baseline and week 30 following a study-specified exercise protocol and read by the Cardiovascular Imaging Core Laboratory (CICL, Boston MA). Change from baseline was determined as per the study statistical analysis plan and compared between treatment arms.
| mmHg | Mavacamten (MYK-461) | Placebo |
|---|---|---|
| Changes From Baseline to Week 30 in Post Exercise in LVOT Peak Gradient. | -47 ± 40.3 | -10 ± 29.6 |
Cardiopulmonary exercise testing (CPET) was performed at baseline and week 30 following a study-specified protocol and peak oxygen consumption (pVO2) was determined by the Cardiovascular Metabolic Disease Research Institute (CMDRI, Palo Alto, CA). Change from baseline was determined as per the study statistical analysis plan and compared between treatment arms.
| mL/kg/min | Mavacamten (MYK-461) | Placebo |
|---|---|---|
| Change From Baseline to Week 30 in pVO2 as Assessed by CPET | 1.4 ± 3.12 | -0.05 ± 3.02 |
New York Heart Association (NYHA) functional classification was determined by the principal investigator at baseline and at specified timepoints in the study. At baseline, all subjects were NYHA Class II or III. For the secondary outcome, NYHA class at Week 30 was compared to baseline and the proportion of subjects with an improvement of at least one class was determined, and the difference between treatment groups was analyzed. The proportion was also multiplied by 100 to provide the result as a percent.
| Participants | Mavacamten (MYK-461) | Placebo |
|---|---|---|
| Proportion of Participants With at Least 1 Class Improvement in NYHA Functional Class From Baseline to Week 30 | 80 | 40 |
The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a patient reported outcome instrument with minimum score = 0 and maximum score = 100 where higher score indicates better health status. There are no units to the score. The instrument utilizes a recall period of 2 weeks over which patients describe the frequency and severity of their symptoms, their physical and social limitations, and how they perceive their heart failure symptoms to affect their quality of life. The KCCQ clinical summary (KCCQ-CS) score, a prespecified secondary outcome of EXPLORER-HCM, combines the physical limitation and total symptom scores.
| Scores on Scale | Mavacamten (MYK-461) | Placebo |
|---|---|---|
| Change From Baseline to Week 30 in Participant-reported Health-related Quality of Life as Assessed by the KCCQ Score | 13.6 ± 14.42 | 4.2 ± 13.68 |
The Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ) is a patient reported outcome instrument that is a daily self-administered 11-item questionnaire. The HCMSQ assesses the core symptoms of HCM (tiredness/fatigue, heart palpitations, chest pain, dizziness, and shortness of breath). The Shortness of Breath domain score, a pre-specified secondary outcome of EXPLORER-HCM, assesses the frequency and severity of shortness of breath. The minimum score = 0 and maximum score = 18 where lower score indicates better health status. There are no units to the score.
| Scores on Scale | Mavacamten (MYK-461) | Placebo |
|---|---|---|
| Change From Baseline to Week 30 in Participant-reported Severity of HCM Symptoms as Assessed by the HCMSQ Score | -2.8 ± 2.68 | -0.9 ± 2.41 |
Collected over Treatment-Emergent Adverse Events (TEAEs) were summarized for the on-treatment period (Day 1 to Week 30) and for the treatment-emergent period (Day 1 to Week 38).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Mavacamten (MYK-461) | 0/123 (0%) | 14/123 (11.4%) | 108/123 (87.8%) |
| Placebo | 1/128 (0.8%) | 12/128 (9.4%) | 104/128 (81.3%) |
| Event | Mavacamten (MYK-461) | Placebo |
|---|---|---|
| Atrial FibrillationCardiac disorders | 3/123 | 5/128 |
| SyncopeNervous system disorders | 3/123 | 1/128 |
| Stress cardiomyopathyCardiac disorders | 2/123 | 0/128 |
| Urinary Tract InfectionInfections and infestations | 0/123 | 2/128 |
| Cardiac FailureCardiac disorders | 1/123 | 0/128 |
| Cardiogenic shockCardiac disorders | 1/123 | 0/128 |
| Pericardial effusionCardiac disorders | 1/123 | 0/128 |
| Systolic dysfunctionCardiac disorders | 1/123 | 0/128 |
| Atrial septal defectCongenital, familial and genetic disorders | 1/123 | 0/128 |
| Abdominal PainGastrointestinal disorders | 1/123 | 0/128 |
| Event | Mavacamten (MYK-461) | Placebo |
|---|---|---|
| DizzinessNervous system disorders | 26/123 | 17/128 |
| NasopharyngitisInfections and infestations | 15/123 | 19/128 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 18/123 | 13/128 |
| HeadacheNervous system disorders | 15/123 | 10/128 |
| Atrial FibrillationCardiac disorders | 10/123 | 10/128 |
| CoughRespiratory, thoracic and mediastinal disorders | 10/123 | 4/128 |
| Back painMusculoskeletal and connective tissue disorders | 10/123 | 8/128 |
| Upper respiratory tract infectionInfections and infestations | 10/123 | 6/128 |
| PalpitationsCardiac disorders | 7/123 | 10/128 |
| SyncopeNervous system disorders | 7/123 | 2/128 |
| Age, Categorical(Participants) | Mavacamten (MYK-461) | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 78 | 88 | 166 |
| >=65 years | 45 | 40 | 85 |
| Age, Continuous(years) | Mavacamten (MYK-461) | Placebo | Total |
|---|---|---|---|
| Median | 60 (26 to 82) | 60 (18 to 81) | 60 (18 to 82) |
| Sex: Female, Male(Participants) | Mavacamten (MYK-461) | Placebo | Total |
|---|---|---|---|
| Female | 57 | 45 | 102 |
| Male | 66 | 83 | 149 |
| Ethnicity (NIH/OMB)(Participants) | Mavacamten (MYK-461) | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 8 | 4 | 12 |
| Not Hispanic or Latino | 114 | 119 | 233 |
| Unknown or Not Reported | 1 | 5 | 6 |
| Race (NIH/OMB)(Participants) | Mavacamten (MYK-461) | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 1 | 1 |
| Asian | 4 | 2 | 6 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 5 | 6 |
| White | 115 | 114 | 229 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 3 | 6 | 9 |
Documents are hosted by the registry — open the source record to download them.
This study is completed, as verified in May 2020. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
MyoKardia, Inc.