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

• ClinicalTrials.gov Identifier: NCT02842242
• Recruitment Status: Completed
• First Posted: July 22, 2016
• Results First Posted: February 5, 2020
• Last Update Posted: June 8, 2021
• Sponsor: MyoKardia, Inc.
• Information provided by (Responsible Party): MyoKardia, Inc.

Tracking Information

• First Submitted Date: July 20, 2016
• First Posted Date: July 22, 2016
• Results First Submitted Date: January 8, 2020
• Results First Posted Date: February 5, 2020
• Last Update Posted Date: June 8, 2021
• Actual Study Start Date: August 2016
• Actual Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 23, 2020)

Change in Post-exercise Peak LVOT Gradient From Baseline to Week 12 [ Time Frame: Baseline and Week 12 ]

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

• Original Primary Outcome Measures (submitted: July 20, 2016): Change in post-exercise peak LVOT gradient from baseline to Week 12 [ Time Frame: 12 weeks ]

Current Secondary Outcome Measures (submitted: January 23, 2020)

• Number of Participants Achieving a Post-exercise Peak LVOT Gradient Response of < 30 mmHg. Gradient < 30 mmHg [ Time Frame: Baseline and Week 12 ]
  LVOT gradients are assessed after a treadmill stress test by echocardiography.
• Change in Dyspnea Symptom Score From Baseline to Week 12 [ Time Frame: Baseline and 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.
• Change in Peak VO2 From Baseline to Week 12 [ Time Frame: Baseline and Week 12 ]
  Peak VO2 is assessed using a cardiopulmonary exercise test.
• Change in VE/VCO2 From Baseline to Week 12 [ Time Frame: Baseline and Week 12 ]
  VE/VCO2 is assessed from cardiopulmonary exercise testing results.
• Change in Resting LVEF From Baseline to Week 12 [ Time Frame: Baseline and Week 12 ]
  LVEF is assessed by echocardiography.
• Change in LV Fractional Shortening (LVFS) From Baseline to Week 12 [ Time Frame: Baseline and Week 12 ]
  LVFS is assessed using echocardiography measures.
• Change in Global Longitudinal Strain (GLS) From Baseline to Week 12 [ Time Frame: Baseline and Week 12 ]
  GLS is assessed using echocardiography measures.
• Change in Post-exercise Peak LVOT Gradient From Week 12 to Week 16 [ Time Frame: Weeks 12 and 16 ]
  Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.

• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: January 23, 2020)

• 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 [ Time Frame: Baseline and Week 12 ]
  Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 2 Open-label Pilot Study Evaluating MYK-461 in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction
• Official Title: A Phase 2 Open-label Pilot Study to Evaluate Efficacy, Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of MYK-461 in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Cardiomyopathy, Hypertrophic Obstructive
• Left Ventricular Outflow Tract Obstruction

• Intervention: Drug: MYK-461

Study Arms

Experimental: Open Label

MYK-461

Intervention: Drug: MYK-461

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 28, 2017): 21
• Original Enrollment: Not Provided
• Actual Study Completion Date: November 2017
• Actual Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02842242
• Other Study ID Numbers: MYK-461-004
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: MyoKardia, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: MyoKardia, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Amy Sehnert, MD; MyoKardia, Inc.

• PRS Account: MyoKardia, Inc.
• Verification Date: June 2021