Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM (NCT NCT05174416)

Last Updated: 2024-09-19

Results Overview

To compare the effect of a 30-week course of mavacamten with placebo on Valsalva LVOT peak gradient as determined by Doppler echocardiography

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

81 participants

Primary outcome timeframe

30 weeks

Results posted on

2024-09-19

Participant Flow

A total of 81 eligible participants were randomly assigned to one of 2 treatment groups, mavacamten or placebo in a ratio of 2:1 (2 mavacamten and 1 placebo). Randomization was stratified according to current treatment at enrollment with a beta-blocker (yes or no)

Participant milestones

Participant milestones
Measure	Mavacamten Mavacamten Capsules Mavacamten: Mavacamten Capsules	Placebo Matching Placebo Capsules Placebo: Matching PBO capsules during placebo controlled period，and mavacamten capsules during long term extension period
Overall Study STARTED	54	27
Overall Study COMPLETED	54	27
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mavacamten n=54 Participants Mavacamten Capsules Mavacamten: Mavacamten Capsules	Placebo n=27 Participants Matching Placebo Capsules Placebo: Matching PBO capsules during placebo controlled period，and mavacamten capsules during long term extension period	Total n=81 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	47 Participants n=99 Participants	23 Participants n=107 Participants	70 Participants n=206 Participants
Age, Categorical >=65 years	7 Participants n=99 Participants	4 Participants n=107 Participants	11 Participants n=206 Participants
Age, Continuous	52.4 years STANDARD_DEVIATION 12.08 • n=99 Participants	51.0 years STANDARD_DEVIATION 11.83 • n=107 Participants	51.9 years STANDARD_DEVIATION 11.94 • n=206 Participants
Sex: Female, Male Female	13 Participants n=99 Participants	10 Participants n=107 Participants	23 Participants n=206 Participants
Sex: Female, Male Male	41 Participants n=99 Participants	17 Participants n=107 Participants	58 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	54 Participants n=99 Participants	27 Participants n=107 Participants	81 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment China	54 participants n=99 Participants	27 participants n=107 Participants	81 participants n=206 Participants
Valsalva LVOT peak gradient	106.78 mmHg STANDARD_DEVIATION 43.225 • n=99 Participants	99.79 mmHg STANDARD_DEVIATION 41.100 • n=107 Participants	104.45 mmHg STANDARD_DEVIATION 42.401 • n=206 Participants

PRIMARY outcome

Timeframe: 30 weeks

To compare the effect of a 30-week course of mavacamten with placebo on Valsalva LVOT peak gradient as determined by Doppler echocardiography

Outcome measures

Outcome measures
Measure	Mavacamten n=54 Participants Mavacamten Capsules Mavacamten: Mavacamten Capsules	Placebo n=27 Participants Matching Placebo Capsules Placebo: Matching PBO capsules during placebo controlled period，and mavacamten capsules during long term extension period
Change From Baseline to Week 30 in Valsalva Left Ventricular Outflow Tract (LVOT) Peak Gradient	-51.05 mmHg Standard Deviation 6.150	19.23 mmHg Standard Deviation 8.535

SECONDARY outcome

Timeframe: 30 weeks

To compare the effect of a 30-week course of mavacamten with placebo on LVOT obstruction.

Outcome measures

Outcome measures
Measure	Mavacamten n=54 Participants Mavacamten Capsules Mavacamten: Mavacamten Capsules	Placebo n=27 Participants Matching Placebo Capsules Placebo: Matching PBO capsules during placebo controlled period，and mavacamten capsules during long term extension period
Change From Baseline to Week 30 in Resting LVOT Peak Gradient	-49.04 mmHg Standard Deviation 4.637	5.95 mmHg Standard Deviation 6.311

SECONDARY outcome

Timeframe: 30 weeks

To compare the effect of a 30-week course of mavacamten with placebo on LVOT obstruction.

Outcome measures

Outcome measures
Measure	Mavacamten n=54 Participants Mavacamten Capsules Mavacamten: Mavacamten Capsules	Placebo n=27 Participants Matching Placebo Capsules Placebo: Matching PBO capsules during placebo controlled period，and mavacamten capsules during long term extension period
Proportion of Participants Achieving a Valsalva LVOT Peak Gradient < 30 mmHg at Week 30	26 Participants	1 Participants

SECONDARY outcome

Timeframe: 30 weeks

To compare the effect of a 30-week course of mavacamten with placebo on LVOT obstruction.

Outcome measures

Outcome measures
Measure	Mavacamten n=54 Participants Mavacamten Capsules Mavacamten: Mavacamten Capsules	Placebo n=27 Participants Matching Placebo Capsules Placebo: Matching PBO capsules during placebo controlled period，and mavacamten capsules during long term extension period
Proportion of Participants Achieving a Valsalva LVOT Peak Gradient < 50 mmHg at Week 30.	32 Participants	2 Participants

SECONDARY outcome

Timeframe: 30 weeks

To compare the effect of a 30-week course of mavacamten with placebo on clinical symptoms

Outcome measures

Outcome measures
Measure	Mavacamten n=54 Participants Mavacamten Capsules Mavacamten: Mavacamten Capsules	Placebo n=27 Participants Matching Placebo Capsules Placebo: Matching PBO capsules during placebo controlled period，and mavacamten capsules during long term extension period
Proportion of Participants With at Least 1 Class Improvement in New York Heart Association (NYHA) Functional Classification From Baseline to Week 30	32 Participants	4 Participants

SECONDARY outcome

Timeframe: 30 weeks

To compare the effect of a 30-week course of Mavacamten with placebo on Participant-Reported health status individually The KCCQ (23-item version) is a patient-reported questionnaire that measures the impact of patients' CV disease or its treatment on 6 distinct domains using a 2-week recall: symptoms/signs, physical limitations, quality of life, social limitations, self-efficacy, and symptom stability (Green et al., 2000). In addition to the individual domains, 2 summary scores can be calculated from the KCCQ: the overall summary score (includes the total symptom, physical limitation, social limitations and quality of life scores) and the clinical summary score (combines the total symptom and physical limitation scales). Scores range from 0 to 100, with higher scores reflecting better health status. The KCCQ will be administered to participants as indicated.

Outcome measures

Outcome measures
Measure	Mavacamten n=54 Participants Mavacamten Capsules Mavacamten: Mavacamten Capsules	Placebo n=27 Participants Matching Placebo Capsules Placebo: Matching PBO capsules during placebo controlled period，and mavacamten capsules during long term extension period
Change From Baseline to Week 30 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)	4.99 score on a scale Standard Deviation 2.063	-5.25 score on a scale Standard Deviation 2.750

SECONDARY outcome

Timeframe: 30 weeks

To compare the effect of a 30-week course of mavacamten on cardiac biomarkers

Outcome measures

Outcome measures
Measure	Mavacamten n=54 Participants Mavacamten Capsules Mavacamten: Mavacamten Capsules	Placebo n=27 Participants Matching Placebo Capsules Placebo: Matching PBO capsules during placebo controlled period，and mavacamten capsules during long term extension period
Change From Baseline to Week 30 in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)	0.182 ng/L Standard Deviation 0.1743	0.932 ng/L Standard Deviation 0.5133

SECONDARY outcome

Timeframe: 30 weeks

To compare the effect of a 30-week course of mavacamten on cardiac biomarkers

Outcome measures

Outcome measures
Measure	Mavacamten n=54 Participants Mavacamten Capsules Mavacamten: Mavacamten Capsules	Placebo n=27 Participants Matching Placebo Capsules Placebo: Matching PBO capsules during placebo controlled period，and mavacamten capsules during long term extension period
Change From Baseline to Week 30 in Cardiac Troponin	0.419 ng/L Standard Deviation 0.1983	1.236 ng/L Standard Deviation 0.6528

SECONDARY outcome

Timeframe: 30 weeks

To compare the effect of a 30-week course of mavacamten with placebo on LV mass evaluated by cardiac magnetic resonance (CMR) imaging.

Outcome measures

Outcome measures
Measure	Mavacamten n=54 Participants Mavacamten Capsules Mavacamten: Mavacamten Capsules	Placebo n=27 Participants Matching Placebo Capsules Placebo: Matching PBO capsules during placebo controlled period，and mavacamten capsules during long term extension period
Change From Baseline to Week 30 in Left Ventricular (LV) Mass Index	-26.365 g/m^2 Standard Deviation 21.0565	4.434 g/m^2 Standard Deviation 14.4226

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Mavacamten

Serious events: 4 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=27 participants at risk Matching Placebo Capsules Placebo: Matching PBO capsules during placebo controlled period，and mavacamten capsules during long term extension period	Mavacamten n=54 participants at risk Mavacamten Capsules Mavacamten: Mavacamten Capsules
Gastrointestinal disorders Haemorrhoids	0.00% 0/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	1.9% 1/54 • Number of events 1 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Cardiac disorders Atrial flutter	0.00% 0/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	1.9% 1/54 • Number of events 1 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Cardiac disorders fibrillation	0.00% 0/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	1.9% 1/54 • Number of events 1 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Vascular disorders Hypotension	0.00% 0/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	1.9% 1/54 • Number of events 1 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	1.9% 1/54 • Number of events 1 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Cardiac disorders Sinus arrest	0.00% 0/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	1.9% 1/54 • Number of events 1 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Cardiac disorders Atrial fibrillation	0.00% 0/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	1.9% 1/54 • Number of events 1 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.

Other adverse events

Additional Information

Prof. Shuyang Zhang

Peking Union Medical College Hospital

Phone: +86 13911667211

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=27 participants at risk Matching Placebo Capsules Placebo: Matching PBO capsules during placebo controlled period，and mavacamten capsules during long term extension period	Mavacamten n=54 participants at risk Mavacamten Capsules Mavacamten: Mavacamten Capsules
Infections and infestations COVID-19	40.7% 11/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	37.0% 20/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Infections and infestations Upper respiratory tract infection	14.8% 4/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	14.8% 8/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Cardiac disorders Defect conduction intraventricular	0.00% 0/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	9.3% 5/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Cardiac disorders Palpitations	7.4% 2/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	5.6% 3/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Cardiac disorders Ventricular extrasystoles	11.1% 3/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	3.7% 2/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Cardiac disorders Cardiac discomfort	0.00% 0/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	5.6% 3/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Cardiac disorders Ventricular tachycardia	7.4% 2/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	3.7% 2/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Metabolism and nutrition disorders Hyperuricemia	7.4% 2/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	13.0% 7/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Metabolism and nutrition disorders Hyperlipidaemia	0.00% 0/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	7.4% 4/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Nervous system disorders Dizziness	7.4% 2/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	13.0% 7/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Nervous system disorders Hypoaesthesia	0.00% 0/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	5.6% 3/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Nervous system disorders Headache	7.4% 2/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	1.9% 1/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Investigations Hepatic enzyme increased	0.00% 0/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	5.6% 3/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Investigations Electrocardiogram QT prolonged	7.4% 2/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	1.9% 1/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Respiratory, thoracic and mediastinal disorders Cough	7.4% 2/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	1.9% 1/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	5.6% 3/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.
Vascular disorders Hypertension	0.00% 0/27 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.	5.6% 3/54 • Adverse events were assessed from the first dose date of study medication up to 30 weeks. Consistent with clinicaltrials.gov definitions.