Trial Outcomes & Findings for A Study of Mavacamten in Obstructive Hypertrophic Cardiomyopathy (NCT NCT05414175)

Last Updated: 2024-12-04

Results Overview

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 doppler echocardiography. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

38 participants

Primary outcome timeframe

At Baseline and Week 30

Results posted on

2024-12-04

Participant Flow

Participant milestones

Participant milestones
Measure	Mavacamten Participants with symptomatic obstructive hypertrophic cardiomyopathy received oral capsule of mavacamten during the treatment period from Day 1 to Week 30. The starting dose of mavacamten was 2.5 milligram (mg) once daily. At Week 6, Week 8, Week 14, and Week 20, mavacamten dose were titrated based on the individual, transthoracic echocardiogram (TTE) response (Valsalva left ventricular outflow tract \[LVOT\] gradient and left ventricular ejection fraction LVEF). The permissible doses during the study were 1, 2.5, 5, 10, or 15 mg.
Overall Study STARTED	38
Overall Study Intent to Treat Population	38
Overall Study Safety Population	38
Overall Study COMPLETED	36
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Mavacamten Participants with symptomatic obstructive hypertrophic cardiomyopathy received oral capsule of mavacamten during the treatment period from Day 1 to Week 30. The starting dose of mavacamten was 2.5 milligram (mg) once daily. At Week 6, Week 8, Week 14, and Week 20, mavacamten dose were titrated based on the individual, transthoracic echocardiogram (TTE) response (Valsalva left ventricular outflow tract \[LVOT\] gradient and left ventricular ejection fraction LVEF). The permissible doses during the study were 1, 2.5, 5, 10, or 15 mg.
Overall Study Withdrawal by Subject	1
Overall Study Other Reasons	1

Baseline Characteristics

A Study of Mavacamten in Obstructive Hypertrophic Cardiomyopathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mavacamten n=38 Participants Participants with symptomatic obstructive hypertrophic cardiomyopathy received oral capsule of mavacamten during the treatment period from Day 1 to Week 30. The starting dose of mavacamten was 2.5 milligram (mg) once daily. At Week 6, Week 8, Week 14, and Week 20, mavacamten dose were titrated based on the individual, transthoracic echocardiogram (TTE) response (Valsalva left ventricular outflow tract \[LVOT\] gradient and left ventricular ejection fraction LVEF). The permissible doses during the study were 1, 2.5, 5, 10, or 15 mg.
Age, Continuous	64.8 years STANDARD_DEVIATION 10.95 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Race/Ethnicity, Customized Japanese	38 participants n=5 Participants

PRIMARY outcome

Timeframe: At Baseline and Week 30

Population: Intent-to-treat population. Only those participants with data available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Mavacamten n=35 Participants Participants with symptomatic obstructive hypertrophic cardiomyopathy received oral capsule of mavacamten during the treatment period from Day 1 to Week 30. The starting dose of mavacamten was 2.5 milligram (mg) once daily. At Week 6, Week 8, Week 14, and Week 20, mavacamten dose were titrated based on the individual, transthoracic echocardiogram (TTE) response (Valsalva left ventricular outflow tract \[LVOT\] gradient and left ventricular ejection fraction LVEF). The permissible doses during the study were 1, 2.5, 5, 10, or 15 mg.
Change From Baseline in Post-exercise Left Ventricular Outflow Tract (LVOT) Peak Gradient at Week 30	-60.6963 millimeters of mercury (mmHg) Standard Deviation 31.55674

SECONDARY outcome

Timeframe: At Baseline and Week 30

Population: Intent to Treat Population. Only those participants with data available at the specified time points were analyzed.

The KCCQ-23 is a 23-item, self-administered questionnaire that measures the impact of a participant's cardiovascular disease or its treatment on 6 distinct domains using a 2-week recall period: symptoms/signs, physical limitation, quality of life (QoL), social limitations, self-efficacy, and symptom stability. The KCCQ 23 Clinical Summary Score (CSS) is derived from the Total Symptom Score (TSS) and the Physical Limitations (PL) score of the KCCQ 23. The CSS, TSS, and the PL score range from 0 to 100 with higher scores representing less severe symptoms and/or physical limitations. The CSS is a mean of the TSS and the PL score. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment.

Outcome measures

Outcome measures
Measure	Mavacamten n=36 Participants Participants with symptomatic obstructive hypertrophic cardiomyopathy received oral capsule of mavacamten during the treatment period from Day 1 to Week 30. The starting dose of mavacamten was 2.5 milligram (mg) once daily. At Week 6, Week 8, Week 14, and Week 20, mavacamten dose were titrated based on the individual, transthoracic echocardiogram (TTE) response (Valsalva left ventricular outflow tract \[LVOT\] gradient and left ventricular ejection fraction LVEF). The permissible doses during the study were 1, 2.5, 5, 10, or 15 mg.
Change From Baseline in Kansas City Cardiomyopathy Questionnaire 23-item Version (KCCQ-23) Clinical Summary Score (CSS) at Week 30	9.766 Score on a Scale Standard Deviation 16.8588

SECONDARY outcome

Timeframe: Baseline and at Week 30

Population: Intent To Treat Population.

The NYHA Functional Classification of Heart Failure (HF) assigns participants to 1 of 4 categories based on the participant's symptoms. Class I (No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea); Class II (Slight limitation of physical activity, Comfortable at rest, Ordinary physical activity results in fatigue, palpitation, dyspnea); Class III (Marked limitation of physical activity, Comfortable at rest, Less-than ordinary-activity causes fatigue, palpitation, or dyspnea) and Class IV (Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases). Improvement is defined as participant moving to lower class category from a higher one. Baseline is defined as last non-missing measurement prior to the first dose.

Outcome measures

Outcome measures
Measure	Mavacamten n=38 Participants Participants with symptomatic obstructive hypertrophic cardiomyopathy received oral capsule of mavacamten during the treatment period from Day 1 to Week 30. The starting dose of mavacamten was 2.5 milligram (mg) once daily. At Week 6, Week 8, Week 14, and Week 20, mavacamten dose were titrated based on the individual, transthoracic echocardiogram (TTE) response (Valsalva left ventricular outflow tract \[LVOT\] gradient and left ventricular ejection fraction LVEF). The permissible doses during the study were 1, 2.5, 5, 10, or 15 mg.
Percentage of Participants With at Least 1 Class Improvement in New York Heart Association (NYHA) Functional Class From Baseline to Week 30	63.2 Percentage of participants

SECONDARY outcome

Timeframe: At baseline and week 30

Population: Intent to Treat Population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected for assessing the concentration of NT-proBNP. Baseline is defined as last non-missing measurement prior to the first dose.

Outcome measures

Outcome measures
Measure	Mavacamten n=36 Participants Participants with symptomatic obstructive hypertrophic cardiomyopathy received oral capsule of mavacamten during the treatment period from Day 1 to Week 30. The starting dose of mavacamten was 2.5 milligram (mg) once daily. At Week 6, Week 8, Week 14, and Week 20, mavacamten dose were titrated based on the individual, transthoracic echocardiogram (TTE) response (Valsalva left ventricular outflow tract \[LVOT\] gradient and left ventricular ejection fraction LVEF). The permissible doses during the study were 1, 2.5, 5, 10, or 15 mg.
Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 30	-738.0 nanogram per liter (ng/L) Interval -3101.0 to 590.0

SECONDARY outcome

Timeframe: At baseline and week 30

Population: Intent to Treat population. Only those participants with data available at the specified time points were analyzed.

Blood samples were collected for assessing cardiac troponins. Baseline is defined as the last non-missing assessment prior to the first dose of the study treatment if both the time of the measurement and the time of first dose are available otherwise it is the last non-missing assessment on or prior to the first dose of the study treatment.

Outcome measures

Outcome measures
Measure	Mavacamten n=36 Participants Participants with symptomatic obstructive hypertrophic cardiomyopathy received oral capsule of mavacamten during the treatment period from Day 1 to Week 30. The starting dose of mavacamten was 2.5 milligram (mg) once daily. At Week 6, Week 8, Week 14, and Week 20, mavacamten dose were titrated based on the individual, transthoracic echocardiogram (TTE) response (Valsalva left ventricular outflow tract \[LVOT\] gradient and left ventricular ejection fraction LVEF). The permissible doses during the study were 1, 2.5, 5, 10, or 15 mg.
Change From Baseline in Cardiac Troponin I at Week 30	-10.920 ng/L Interval -226.42 to 0.8

SECONDARY outcome

Timeframe: At baseline and week 30

Population: Intent to Treat Population. Only those participants with data available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	Mavacamten n=36 Participants Participants with symptomatic obstructive hypertrophic cardiomyopathy received oral capsule of mavacamten during the treatment period from Day 1 to Week 30. The starting dose of mavacamten was 2.5 milligram (mg) once daily. At Week 6, Week 8, Week 14, and Week 20, mavacamten dose were titrated based on the individual, transthoracic echocardiogram (TTE) response (Valsalva left ventricular outflow tract \[LVOT\] gradient and left ventricular ejection fraction LVEF). The permissible doses during the study were 1, 2.5, 5, 10, or 15 mg.
Change From Baseline in Cardiac Troponin T at Week 30	-4.95 ng/L Interval -19.2 to 0.3

Adverse Events

Mavacamten

Serious events: 6 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Mavacamten n=38 participants at risk Participants with symptomatic obstructive hypertrophic cardiomyopathy received oral capsule of mavacamten during the treatment period from Day 1 to Week 30. The starting dose of mavacamten was 2.5 milligram (mg) once daily. At Week 6, Week 8, Week 14, and Week 20, mavacamten dose were titrated based on the individual, transthoracic echocardiogram (TTE) response (Valsalva left ventricular outflow tract \[LVOT\] gradient and left ventricular ejection fraction LVEF). The permissible doses during the study were 1, 2.5, 5, 10, or 15 mg.
Cardiac disorders Atrial fibrillation	2.6% 1/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Eye disorders Macular oedema	2.6% 1/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Hepatobiliary disorders Cholangitis	2.6% 1/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Hepatobiliary disorders Cholecystitis acute	2.6% 1/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Infections and infestations COVID-19	2.6% 1/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Infections and infestations Colonic abscess	2.6% 1/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	2.6% 1/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Nervous system disorders Cerebral haemorrhage	2.6% 1/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.

Other adverse events

Other adverse events
Measure	Mavacamten n=38 participants at risk Participants with symptomatic obstructive hypertrophic cardiomyopathy received oral capsule of mavacamten during the treatment period from Day 1 to Week 30. The starting dose of mavacamten was 2.5 milligram (mg) once daily. At Week 6, Week 8, Week 14, and Week 20, mavacamten dose were titrated based on the individual, transthoracic echocardiogram (TTE) response (Valsalva left ventricular outflow tract \[LVOT\] gradient and left ventricular ejection fraction LVEF). The permissible doses during the study were 1, 2.5, 5, 10, or 15 mg.
Cardiac disorders Atrial fibrillation	7.9% 3/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Cardiac disorders Palpitations	5.3% 2/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Eye disorders Cataract	5.3% 2/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	5.3% 2/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
General disorders Malaise	5.3% 2/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
General disorders Pyrexia	7.9% 3/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Infections and infestations Bronchitis	5.3% 2/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Infections and infestations COVID-19	21.1% 8/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Infections and infestations Nasopharyngitis	15.8% 6/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	5.3% 2/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	5.3% 2/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis contact	5.3% 2/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.
Vascular disorders Hypertension	7.9% 3/38 • All-cause mortality was measured from first dose up until approximately 66 weeks post-first dose. SAEs and Other AEs were collected from first dose till last dose plus 140 days (up to approximately 50 weeks). Safety analysis population included all participants who receive at least one dose of study drug.

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER