CompletedNCT02842242PIONEER-HCMUpdated Jun 8, 2021Results posted

A Phase 2 Open-label Pilot Study Evaluating MYK-461 in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction

A Phase 2 interventional study of MYK-461 in Cardiomyopathy, Hypertrophic Obstructive and Left Ventricular Outflow Tract Obstruction, sponsored by MyoKardia, Inc.. Completed at 7 sites in United States. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2021-06-08.

Sponsored by MyoKardia, Inc. (part of Bristol-Myers Squibb) · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 21
Allocation: Not applicable
Ages: 18 Years to 70 Years
Sex: All

Study summary

The purpose of this phase 2 open-label pilot study is to evaluate the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of MYK-461 in subjects with symptomatic HCM and LVOT obstruction aged 18-70 years.

Conditions studied

Cardiomyopathy, Hypertrophic Obstructive
Left Ventricular Outflow Tract Obstruction

Browse trials for

Cardiomyopathy, Hypertrophic 353

In context

Cardiomyopathy, Hypertrophic

353 studies on the registry are indexed under Cardiomyopathy, Hypertrophic; 113 are open to participants now.

This study's enrollment of 21 is below the median of 56 across 173 interventional studies indexed under Cardiomyopathy, Hypertrophic.

Browse Cardiomyopathy, Hypertrophic studies →

Lead sponsor

MyoKardia, Inc. is the lead sponsor of 7 studies on the registry; none are open to participants now.

First submitted before MyoKardia, Inc. became part of Bristol-Myers Squibb.

Browse MyoKardia, Inc. studies →All Bristol-Myers Squibb studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 70 Years
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Key Inclusion Criteria:

Diagnosed with HCM (hypertrophied and non-dilated left ventricle in absence of systemic or other known cause), with LV wall thickness ≥ 15 mm at time of initial diagnosis or ≥ 13 mm with a positive family history of HCM.
Age 18-70
BMI 18-37kg/m2
Documented LVEF ≥ 55% at the Screening visit as determined by the investigator and the investigational site's echocardiography laboratory.
Resting LVOT gradient ≥ 30 mg Hg and post-exercise peak LVOT gradient ≥ 50 mm Hg
NYHA functional class II or higher

Key Exclusion Criteria:

History of sustained ventricular tachyarrhythmia.
History of syncope with exercise within past 6 months.
Active infection.
Persistent atrial fibrillation or atrial fibrillation at Screening or history of paroxysmal atrial fibrillation with resting rate document > 100bpm within 1 year of screening.
Has QTc Fridericia (QTcF) > 500 ms, or any other ECG abnormality considered by the investigator to pose a risk to subject safety (e.g. second degree atrioventricular block type II).
Aortic stenosis or fixed subaortic obstruction.
History of LV systolic dysfunction (LVEF \< 45%) at any time during their clinical course.
History of obstructive coronary artery disease.
History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator or MyoKardia physician, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
Part A: Ongoing therapy with beta blockers, calcium channel blockers, or disopyramide. Subjects on any of these medications who, in the opinion of the investigator, can safely be withdrawn are eligible as long as medication is discontinued at least 14 days prior to the Screening visit.
Part B: Ongoing therapy with calcium channel blockers or disopyramide. Subjects on any of these medications who, in the opinion of the investigator, can safely be withdrawn are eligible as long as medication is discontinued at least 14 days prior to the Screening visit.
Prior treatment with cardiotoxic agents such as doxorubicin or similar, or current treatment with antiarrhythmic drugs that have negative inotropic activity, e.g. flecainide or propafenone.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 21 participants (actual)

Study arms

Experimental
Open Label
MYK-461
Drug: MYK-461

Interventions

DrugMYK-461

What researchers measure

Primary outcomes

Change in Post-exercise Peak LVOT Gradient From Baseline to Week 12
Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.
Time frame: Baseline and Week 12

Secondary outcomes

Number of Participants Achieving a Post-exercise Peak LVOT Gradient Response of < 30 mmHg. Gradient < 30 mmHg
LVOT gradients are assessed after a treadmill stress test by echocardiography.
Time frame: Baseline and Week 12
Change in Dyspnea Symptom Score From Baseline to Week 12
The scale name is Dyspnea Numeric Rating Scale (NRS). It is intended to measure how much shortness of breath you have had in the past week. 0 = no shortness of breath and 10 = shortness of breath as the worst possible.
Time frame: Baseline and Week 12
Change in Peak VO2 From Baseline to Week 12
Peak VO2 is assessed using a cardiopulmonary exercise test.
Time frame: Baseline and Week 12
Change in VE/VCO2 From Baseline to Week 12
VE/VCO2 is assessed from cardiopulmonary exercise testing results.
Time frame: Baseline and Week 12
Change in Resting LVEF From Baseline to Week 12
LVEF is assessed by echocardiography.
Time frame: Baseline and Week 12
Change in LV Fractional Shortening (LVFS) From Baseline to Week 12
LVFS is assessed using echocardiography measures.
Time frame: Baseline and Week 12
Change in Global Longitudinal Strain (GLS) From Baseline to Week 12
GLS is assessed using echocardiography measures.
Time frame: Baseline and Week 12
Change in Post-exercise Peak LVOT Gradient From Week 12 to Week 16
Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.
Time frame: Weeks 12 and 16

Other outcomes

Change in NYHA Functional Class From Baseline to Week 12
Time frame: Baseline and Week 12
Change in KCCQ OSS From Baseline to Week 12
Time frame: Baseline and Week 12
Change in NT-proBNP From Baseline to Week 12
Time frame: 12 weeks
Number of Subjects Achieving an LVOT Gradient Response of Post-exercise Peak Gradient < 10 mmHg at Week 12
Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.
Time frame: Baseline and Week 12

Results

Posted Feb 5, 2020

Participant flow

Participant flow — Overall Study
Milestone	Cohort A	Cohort B
Started	11	10
Completed	10	10
Not completed	1	0

Outcome measures

PrimaryChange in Post-exercise Peak LVOT Gradient From Baseline to Week 12

Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.

Time frame:: Baseline and Week 12
Reported as:: Mean · mm Hg

Change in Post-exercise Peak LVOT Gradient From Baseline to Week 12
mm Hg	Cohort A	Cohort B
Change in Post-exercise Peak LVOT Gradient From Baseline to Week 12	-89.5 (-138.3 to -40.7)	-25.0 (-47.1 to -3.0)

SecondaryNumber of Participants Achieving a Post-exercise Peak LVOT Gradient Response of < 30 mmHg. Gradient < 30 mmHg

LVOT gradients are assessed after a treadmill stress test by echocardiography.

Time frame:: Baseline and Week 12
Reported as:: Count of participants · Participants

Number of Participants Achieving a Post-exercise Peak LVOT Gradient Response of < 30 mmHg. Gradient < 30 mmHg
Participants	Cohort A	Cohort B
Number of Participants Achieving a Post-exercise Peak LVOT Gradient Response of < 30 mmHg. Gradient < 30 mmHg	8	0

SecondaryChange in Dyspnea Symptom Score From Baseline to Week 12

The scale name is Dyspnea Numeric Rating Scale (NRS). It is intended to measure how much shortness of breath you have had in the past week. 0 = no shortness of breath and 10 = shortness of breath as the worst possible.

Time frame:: Baseline and Week 12
Reported as:: Mean · units on a scale

Change in Dyspnea Symptom Score From Baseline to Week 12
units on a scale	Cohort A	Cohort B
Change in Dyspnea Symptom Score From Baseline to Week 12	-3.1 (-4.1 to -2.1)	-3.0 (-5.0 to -1.0)

SecondaryChange in Peak VO2 From Baseline to Week 12

Peak VO2 is assessed using a cardiopulmonary exercise test.

Time frame:: Baseline and Week 12
Reported as:: Mean · mL/kg/min

Change in Peak VO2 From Baseline to Week 12
mL/kg/min	Cohort A	Cohort B
Change in Peak VO2 From Baseline to Week 12	3.5 (1.2 to 5.9)	1.7 (0.03 to 3.3)

SecondaryChange in VE/VCO2 From Baseline to Week 12

VE/VCO2 is assessed from cardiopulmonary exercise testing results.

Time frame:: Baseline and Week 12
Reported as:: Mean · Ratio

Change in VE/VCO2 From Baseline to Week 12
Ratio	Cohort A	Cohort B
Change in VE/VCO2 From Baseline to Week 12	-2.2 (-6.1 to 1.7)	-2.5 (-4.3 to -0.7)

SecondaryChange in Resting LVEF From Baseline to Week 12

LVEF is assessed by echocardiography.

Time frame:: Baseline and Week 12
Reported as:: Mean · Percent change

Change in Resting LVEF From Baseline to Week 12
Percent change	Cohort A	Cohort B
Change in Resting LVEF From Baseline to Week 12	-14.6 (-23.1 to -6.2)	-5.5 (-9.8 to -1.2)

SecondaryChange in LV Fractional Shortening (LVFS) From Baseline to Week 12

LVFS is assessed using echocardiography measures.

Time frame:: Baseline and Week 12
Reported as:: Mean · Percent

Change in LV Fractional Shortening (LVFS) From Baseline to Week 12
Percent	Cohort A	Cohort B
Change in LV Fractional Shortening (LVFS) From Baseline to Week 12	-18.60 ± 13.05	-3.98 ± 11.42

SecondaryChange in Global Longitudinal Strain (GLS) From Baseline to Week 12

GLS is assessed using echocardiography measures.

Time frame:: Baseline and Week 12
Reported as:: Mean · Percent

Change in Global Longitudinal Strain (GLS) From Baseline to Week 12
Percent	Cohort A	Cohort B
Change in Global Longitudinal Strain (GLS) From Baseline to Week 12	0.56 ± 3.778	0.18 ± 2.806

SecondaryChange in Post-exercise Peak LVOT Gradient From Week 12 to Week 16

Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.

Time frame:: Weeks 12 and 16
Reported as:: Mean · mm Hg

Change in Post-exercise Peak LVOT Gradient From Week 12 to Week 16
mm Hg	Cohort A	Cohort B
Change in Post-exercise Peak LVOT Gradient From Week 12 to Week 16	55.22 ± 40.84	84.08 ± 28.38

Other pre-specifiedChange in NYHA Functional Class From Baseline to Week 12

Time frame:: Baseline and Week 12

Results for this outcome have not been posted.

Other pre-specifiedChange in KCCQ OSS From Baseline to Week 12

Time frame:: Baseline and Week 12

Results for this outcome have not been posted.

Other pre-specifiedChange in NT-proBNP From Baseline to Week 12

Time frame:: 12 weeks

Results for this outcome have not been posted.

Other pre-specifiedNumber of Subjects Achieving an LVOT Gradient Response of Post-exercise Peak Gradient < 10 mmHg at Week 12

Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.

Time frame:: Baseline and Week 12

Results for this outcome have not been posted.

Adverse events

Collected over 16 Weeks. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cohort A	0/11 (0%)	1/11 (9.1%)	10/11 (90.9%)
Cohort B	0/10 (0%)	0/10 (0%)	10/10 (100%)

Most frequent serious events

Most frequent serious events
Event	Cohort A	Cohort B
Atrial FibrillationCardiac disorders	1/11	0/10

Most frequent other events

Showing 10 of 73

Most frequent other events
Event	Cohort A	Cohort B
Ventricular TachycardiaCardiac disorders	1/11	4/10
DizzinessNervous system disorders	1/11	3/10
Atrial FibrillationCardiac disorders	3/11	1/10
HeadacheNervous system disorders	3/11	2/10
Ejection Fraction DecreasedInvestigations	3/11	0/10
Angina PectorisCardiac disorders	0/11	2/10
FatigueGeneral disorders	2/11	2/10
Application Site RashGeneral disorders	0/11	2/10
Upper Respiratory Tract InfectionInfections and infestations	1/11	2/10
NauseaGastrointestinal disorders	2/11	0/10

Baseline characteristics

Age, Customized
Age, Customized(years)	Cohort A	Cohort B	Total
Mean Age (range)	56 (22 to 70)	58 (26 to 67)	57 (22 to 70)

Sex/Gender, Customized
Sex/Gender, Customized(Participants)	Cohort A	Cohort B	Total
Male	7	5	12
Female	4	5	9

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Cohort A	Cohort B	Total
Hispanic or Latino	0	0	0
Not Hispanic or Latino	11	10	21
Unknown or Not Reported	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Cohort A	Cohort B	Total
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	1	1
White	11	9	20
More than one race	0	0	0
Unknown or Not Reported	0	0	0

Postexercise LVOT gradient
Postexercise LVOT gradient(mm Hg)	Cohort A	Cohort B	Total
Mean	103 ± 50	86 ± 43	94.5 ± 0

Study locations

7 sites

Mayo Clinic Arizona
Scottsdale, Arizona, United States
Yale New Haven Hospital
New Haven, Connecticut, United States
Tufts Medical Center
Boston, Massachusetts, United States
Washington University St. Louis
St Louis, Missouri, United States
Duke Health Center at Southpoint
Durham, North Carolina, United States
Oregon Health and Science University
Portland, Oregon, United States
Hospital of the University of Pennsylvania (Penn Heart and Vascular Center)
Philadelphia, Pennsylvania, United States

References and documents

Publications

Heitner SB, Jacoby D, Lester SJ, Owens A, Wang A, Zhang D, Lambing J, Lee J, Semigran M, Sehnert AJ. Mavacamten Treatment for Obstructive Hypertrophic Cardiomyopathy: A Clinical Trial. Ann Intern Med. 2019 Jun 4;170(11):741-748. doi: 10.7326/M18-3016. Epub 2019 Apr 30. PubMed 31035291 ↗

Study documents

Study protocol · May 5, 2017
Statistical analysis plan · Oct 24, 2017

Documents are hosted by the registry — open the source record to download them.

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Aug 2016 to primary completion in Nov 2017, 15 months.

Results were first posted in Feb 2020, 2 years 3 months after primary completion. A results delay was requested in Nov 2018.

Of 21 phase 2 interventional studies under Cardiomyopathy, Hypertrophic, half reached primary completion within 37 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 43. This study's 15 months is below that.

How these figures are worked out, and which studies are left out of them.

Registered: Jul 20, 2016
First posted: Jul 22, 2016
StartActual: Aug 2016
Primary completionActual: Nov 2017
CompletionActual: Nov 2017
Results delay requested: Nov 19, 2018
Results first posted: Feb 5, 2020
Last update: Jun 8, 2021

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Jun 8, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02842242
Lead sponsor: MyoKardia, Inc.
Responsible party: Sponsor
First posted: Jul 22, 2016
Start date: Aug 2016
Primary completion: Nov 2017
Completion: Nov 2017
Results posted: Feb 5, 2020
Last update: Jun 8, 2021

Study contacts

Amy Sehnert, MD

study chair · MyoKardia, Inc.

View the source record on ClinicalTrials.gov ↗

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