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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Information provided by (Responsible Party):
MyoKardia, Inc.

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Cardiomyopathy, Hypertrophic Obstructive
Left Ventricular Outflow Tract Obstruction
Intervention Drug: MYK-461
Enrollment 21
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort A Cohort B
Hide Arm/Group Description Mavacamten 10 to 20 mg/d without background medications Mavacamten 2 to 5 mg/d with beta-blockers allowed.
Period Title: Overall Study
Started 11 10
Completed 10 10
Not Completed 1 0
Arm/Group Title Cohort A Cohort B Total
Hide Arm/Group Description Mavacamten 10 to 20 mg/d without background medications Mavacamten 2 to 5 mg/d with beta-blockers allowed. Total of all reporting groups
Overall Number of Baseline Participants 11 10 21
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Mean (Full Range)
Unit of measure:  Years
Mean Age (range) Number Analyzed 11 participants 10 participants 21 participants
56
(22 to 70)
58
(26 to 67)
57
(22 to 70)
Sex/Gender, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Male Number Analyzed 11 participants 10 participants 21 participants
7
  63.6%
5
  50.0%
12
  57.1%
Female Number Analyzed 11 participants 10 participants 21 participants
4
  36.4%
5
  50.0%
9
  42.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 10 participants 21 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
11
 100.0%
10
 100.0%
21
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 10 participants 21 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
  10.0%
1
   4.8%
White
11
 100.0%
9
  90.0%
20
  95.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Postexercise LVOT gradient   [1] 
Mean (Standard Deviation)
Unit of measure:  Mm Hg
Number Analyzed 9 participants 9 participants 18 participants
103  (50) 86  (43) 94.5  (0)
[1]
Measure Analysis Population Description: Based on available data
1.Primary Outcome
Title Change in Post-exercise Peak LVOT Gradient From Baseline to Week 12
Hide Description Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort A Cohort B
Hide Arm/Group Description:
Mavacamten 10 to 20 mg/d without background medications
Mavacamten 2 to 5 mg/d with beta-blockers allowed.
Overall Number of Participants Analyzed 8 9
Mean (95% Confidence Interval)
Unit of Measure: mm Hg
-89.5
(-138.3 to -40.7)
-25.0
(-47.1 to -3.0)
2.Secondary Outcome
Title Number of Participants Achieving a Post-exercise Peak LVOT Gradient Response of < 30 mmHg. Gradient < 30 mmHg
Hide Description LVOT gradients are assessed after a treadmill stress test by echocardiography.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort A Cohort B
Hide Arm/Group Description:
Mavacamten 10 to 20 mg/d without background medications
Mavacamten 2 to 5 mg/d with beta-blockers allowed.
Overall Number of Participants Analyzed 11 10
Measure Type: Count of Participants
Unit of Measure: Participants
8
  72.7%
0
   0.0%
3.Secondary Outcome
Title Change in Dyspnea Symptom Score From Baseline to Week 12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort A Cohort B
Hide Arm/Group Description:
Mavacamten 10 to 20 mg/d without background medications
Mavacamten 2 to 5 mg/d with beta-blockers allowed.
Overall Number of Participants Analyzed 10 10
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-3.1
(-4.1 to -2.1)
-3.0
(-5.0 to -1.0)
4.Secondary Outcome
Title Change in Peak VO2 From Baseline to Week 12
Hide Description Peak VO2 is assessed using a cardiopulmonary exercise test.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort A Cohort B
Hide Arm/Group Description:
Mavacamten 10 to 20 mg/d without background medications
Mavacamten 2 to 5 mg/d with beta-blockers allowed.
Overall Number of Participants Analyzed 10 10
Mean (95% Confidence Interval)
Unit of Measure: mL/kg/min
3.5
(1.2 to 5.9)
1.7
(0.03 to 3.3)
5.Secondary Outcome
Title Change in VE/VCO2 From Baseline to Week 12
Hide Description VE/VCO2 is assessed from cardiopulmonary exercise testing results.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort A Cohort B
Hide Arm/Group Description:
Mavacamten 10 to 20 mg/d without background medications
Mavacamten 2 to 5 mg/d with beta-blockers allowed.
Overall Number of Participants Analyzed 10 10
Mean (95% Confidence Interval)
Unit of Measure: Ratio
-2.2
(-6.1 to 1.7)
-2.5
(-4.3 to -0.7)
6.Secondary Outcome
Title Change in Resting LVEF From Baseline to Week 12
Hide Description LVEF is assessed by echocardiography.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort A Cohort B
Hide Arm/Group Description:
Mavacamten 10 to 20 mg/d without background medications
Mavacamten 2 to 5 mg/d with beta-blockers allowed.
Overall Number of Participants Analyzed 10 10
Mean (95% Confidence Interval)
Unit of Measure: Percent change
-14.6
(-23.1 to -6.2)
-5.5
(-9.8 to -1.2)
7.Secondary Outcome
Title Change in LV Fractional Shortening (LVFS) From Baseline to Week 12
Hide Description LVFS is assessed using echocardiography measures.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort A Cohort B
Hide Arm/Group Description:
Mavacamten 10 to 20 mg/d without background medications
Mavacamten 2 to 5 mg/d with beta-blockers allowed.
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: Percent
-18.60  (13.05) -3.98  (11.42)
8.Secondary Outcome
Title Change in Global Longitudinal Strain (GLS) From Baseline to Week 12
Hide Description GLS is assessed using echocardiography measures.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort A Cohort B
Hide Arm/Group Description:
Mavacamten 10 to 20 mg/d without background medications
Mavacamten 2 to 5 mg/d with beta-blockers allowed.
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: Percent
0.56  (3.778) 0.18  (2.806)
9.Secondary Outcome
Title Change in Post-exercise Peak LVOT Gradient From Week 12 to Week 16
Hide Description Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.
Time Frame Weeks 12 and 16
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort A Cohort B
Hide Arm/Group Description:
Mavacamten 10 to 20 mg/d without background medications
Mavacamten 2 to 5 mg/d with beta-blockers allowed.
Overall Number of Participants Analyzed 8 10
Mean (Standard Deviation)
Unit of Measure: mm Hg
55.22  (40.84) 84.08  (28.38)
10.Other Pre-specified Outcome
Title Change in NYHA Functional Class From Baseline to Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Outcome Measure Data Not Reported
11.Other Pre-specified Outcome
Title Change in KCCQ OSS From Baseline to Week 12
Hide Description [Not Specified]
Time Frame Baseline and Week 12
Outcome Measure Data Not Reported
12.Other Pre-specified Outcome
Title Change in NT-proBNP From Baseline to Week 12
Hide Description [Not Specified]
Time Frame 12 weeks
Outcome Measure Data Not Reported
13.Other Pre-specified Outcome
Title Number of Subjects Achieving an LVOT Gradient Response of Post-exercise Peak Gradient < 10 mmHg at Week 12
Hide Description Post-exercise peak LVOT gradients are assessed after a treadmill stress test by echocardiography.
Time Frame Baseline and Week 12
Outcome Measure Data Not Reported
Time Frame 16 Weeks
Adverse Event Reporting Description Adverse event data were collected from baseline through the end of study visit at Week 16 for each participant enrolled.
 
Arm/Group Title Cohort A Cohort B
Hide Arm/Group Description Mavacamten 10 to 20 mg/d without background medications Mavacamten 2 to 5 mg/d with beta-blockers allowed.
All-Cause Mortality
Cohort A Cohort B
Affected / at Risk (%) Affected / at Risk (%)
Total   0/11 (0.00%)   0/10 (0.00%) 
Hide Serious Adverse Events
Cohort A Cohort B
Affected / at Risk (%) Affected / at Risk (%)
Total   1/11 (9.09%)   0/10 (0.00%) 
Cardiac disorders     
Atrial Fibrillation †  1/11 (9.09%)  0/10 (0.00%) 
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort A Cohort B
Affected / at Risk (%) Affected / at Risk (%)
Total   10/11 (90.91%)   10/10 (100.00%) 
Cardiac disorders     
Ventricular Tachycardia †  1/11 (9.09%)  4/10 (40.00%) 
Atrial Fibrillation †  3/11 (27.27%)  1/10 (10.00%) 
Angina Pectoris †  0/11 (0.00%)  2/10 (20.00%) 
Cardiac Failure †  1/11 (9.09%)  0/10 (0.00%) 
Cardiac Flutter †  1/11 (9.09%)  0/10 (0.00%) 
Palpitations †  1/11 (9.09%)  0/10 (0.00%) 
Tachycardia †  1/11 (9.09%)  0/10 (0.00%) 
Ventricular extrasystoles †  1/11 (9.09%)  0/10 (0.00%) 
Eye disorders     
Visual impairment †  1/11 (9.09%)  0/10 (0.00%) 
Gastrointestinal disorders     
Nausea †  2/11 (18.18%)  0/10 (0.00%) 
Abdominal Discomfort †  1/11 (9.09%)  0/10 (0.00%) 
Constipation †  0/11 (0.00%)  1/10 (10.00%) 
Diarrhoea †  0/11 (0.00%)  1/10 (10.00%) 
Food Poisoning †  1/11 (9.09%)  0/10 (0.00%) 
Gastric Ulcer †  1/11 (9.09%)  0/10 (0.00%) 
Gastritis †  0/11 (0.00%)  1/10 (10.00%) 
Retching †  1/11 (9.09%)  0/10 (0.00%) 
Vomiting †  1/11 (9.09%)  0/10 (0.00%) 
General disorders     
Fatigue †  2/11 (18.18%)  2/10 (20.00%) 
Application Site Rash †  0/11 (0.00%)  2/10 (20.00%) 
Application Site Erythema †  1/11 (9.09%)  0/10 (0.00%) 
Asthenia †  1/11 (9.09%)  1/10 (10.00%) 
Chills †  1/11 (9.09%)  0/10 (0.00%) 
Feeling Abnormal †  1/11 (9.09%)  0/10 (0.00%) 
Oedema peripheral †  1/11 (9.09%)  0/10 (0.00%) 
Peripheral Swelling †  0/11 (0.00%)  1/10 (10.00%) 
Infections and infestations     
Upper Respiratory Tract Infection †  1/11 (9.09%)  2/10 (20.00%) 
Urinary Tract Infection †  2/11 (18.18%)  0/10 (0.00%) 
Nasopharyngitis †  0/11 (0.00%)  1/10 (10.00%) 
Sinusitis †  0/11 (0.00%)  1/10 (10.00%) 
Tooth infection †  0/11 (0.00%)  1/10 (10.00%) 
Injury, poisoning and procedural complications     
Contusion †  0/11 (0.00%)  1/10 (10.00%) 
Fall †  1/11 (9.09%)  1/10 (10.00%) 
Heat exhaustion †  0/11 (0.00%)  1/10 (10.00%) 
Laceration †  0/11 (0.00%)  1/10 (10.00%) 
Muscle strain †  0/11 (0.00%)  1/10 (10.00%) 
Rib fracture †  0/11 (0.00%)  1/10 (10.00%) 
Investigations     
Ejection Fraction Decreased †  3/11 (27.27%)  0/10 (0.00%) 
Blood bilirubin increased †  0/11 (0.00%)  1/10 (10.00%) 
Blood calcium decreased †  0/11 (0.00%)  1/10 (10.00%) 
Blood creatine phosphokinase abnormal †  1/11 (9.09%)  0/10 (0.00%) 
Brain natriuretic peptide increased †  1/11 (9.09%)  1/10 (10.00%) 
Heart rate irregular †  1/11 (9.09%)  1/10 (10.00%) 
Musculoskeletal and connective tissue disorders     
Joint swelling †  0/11 (0.00%)  1/10 (10.00%) 
Muscular weakness †  1/11 (9.09%)  0/10 (0.00%) 
Myalgia †  1/11 (9.09%)  0/10 (0.00%) 
Pain in extremity †  0/11 (0.00%)  1/10 (10.00%) 
Nervous system disorders     
Headache †  3/11 (27.27%)  2/10 (20.00%) 
Dizziness †  1/11 (9.09%)  3/10 (30.00%) 
Hypersomnia †  0/11 (0.00%)  1/10 (10.00%) 
Hyporeflexia †  0/11 (0.00%)  1/10 (10.00%) 
Paraesthesia †  0/11 (0.00%)  1/10 (10.00%) 
Presyncope †  0/11 (0.00%)  1/10 (10.00%) 
Tremor †  1/11 (9.09%)  0/10 (0.00%) 
Psychiatric disorders     
Anxiety †  1/11 (9.09%)  0/10 (0.00%) 
Insomnia †  0/11 (0.00%)  1/10 (10.00%) 
Reproductive system and breast disorders     
Breast mass †  0/11 (0.00%)  1/10 (10.00%) 
Breast pain †  0/11 (0.00%)  1/10 (10.00%) 
Vaginal discharge †  0/11 (0.00%)  1/10 (10.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnea (Exertional) †  2/11 (18.18%)  0/10 (0.00%) 
Cough †  1/11 (9.09%)  1/10 (10.00%) 
Dyspnoea †  1/11 (9.09%)  0/10 (0.00%) 
Oropharyngeal pain †  0/11 (0.00%)  1/10 (10.00%) 
Productive cough †  0/11 (0.00%)  1/10 (10.00%) 
Rhinorrhoea †  1/11 (9.09%)  1/10 (10.00%) 
Sinus congestion †  1/11 (9.09%)  0/10 (0.00%) 
Throat irritation †  1/11 (9.09%)  1/10 (10.00%) 
Upper-airway cough syndrome †  1/11 (9.09%)  0/10 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash †  2/11 (18.18%)  0/10 (0.00%) 
Cold sweat †  1/11 (9.09%)  0/10 (0.00%) 
Dermatitis †  1/11 (9.09%)  0/10 (0.00%) 
Dermatitis contact †  0/11 (0.00%)  1/10 (10.00%) 
Vascular disorders     
Hypertension †  1/11 (9.09%)  1/10 (10.00%) 
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
PI's have the right to publish data after the primary publication is released.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Amy Sehnert
Organization: MyoKardia Inc.
Phone: 650-741-7798
EMail: asehnert@myokardia.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: MyoKardia, Inc.
ClinicalTrials.gov Identifier: NCT02842242    
Other Study ID Numbers: MYK-461-004
First Submitted: July 20, 2016
First Posted: July 22, 2016
Results First Submitted: January 8, 2020
Results First Posted: February 5, 2020
Last Update Posted: June 8, 2021