Cardiomyopathy, Hypertrophic ObstructivePhase 2PIONEER-HCMNCT02842242
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 study testing MYK-461 in people with Cardiomyopathy, Hypertrophic Obstructive and Left Ventricular Outflow Tract Obstruction, run by MyoKardia, Inc. at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Cardiomyopathy, Hypertrophic Obstructive, Left Ventricular Outflow Tract Obstruction
- What is being tested?
- MYK-461
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 7 sitesUnited States
- Study dates
- Aug 2016to Nov 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Tufts Medical Center
Boston, Massachusetts
Duke Health Center at Southpoint
Durham, North Carolina
Yale New Haven Hospital
New Haven, Connecticut
Hospital of the University of Pennsylvania (Penn Heart and Vascular Center)
Philadelphia, Pennsylvania
Oregon Health and Science University
Portland, Oregon
Mayo Clinic Arizona
Scottsdale, Arizona
Washington University St. Louis
St Louis, Missouri
About this study
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
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.
- Being tested
- MYK-461
- Medical subject headings
- Cardiomyopathy, Hypertrophic, Ventricular Outflow Obstruction, Left
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MYK-461Drug
| Study group | Role | What they receive |
|---|---|---|
| Open Label | Experimental | MYK-461 Receives: Drug: MYK-461 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Week 12
Secondary outcomes (8)
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.
Measured: 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.
Measured: Baseline and Week 12
Change in Peak VO2 From Baseline to Week 12
Peak VO2 is assessed using a cardiopulmonary exercise test.
Measured: Baseline and Week 12
Change in VE/VCO2 From Baseline to Week 12
VE/VCO2 is assessed from cardiopulmonary exercise testing results.
Measured: Baseline and Week 12
Change in Resting LVEF From Baseline to Week 12
LVEF is assessed by echocardiography.
Measured: Baseline and Week 12
Change in LV Fractional Shortening (LVFS) From Baseline to Week 12
LVFS is assessed using echocardiography measures.
Measured: Baseline and Week 12
Change in Global Longitudinal Strain (GLS) From Baseline to Week 12
GLS is assessed using echocardiography measures.
Measured: 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.
Measured: Weeks 12 and 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2016 (estimated)
- Study startAug 2016
- Primary completionNov 2017
- Study completionNov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiomyopathy, Hypertrophic ObstructiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- MyoKardia, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Amy Sehnert, MD, Study chair, MyoKardia, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02842242
- Sponsor's protocol ID
- MYK-461-004
- Acronym
- PIONEER-HCM
- Status last verified
- Jun 2021
- First submitted
- 20 Jul 2016
- Last updated
- 8 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
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 at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02842242
- Acronym / sponsor ID
- PIONEER-HCM / MYK-461-004
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- MyoKardia, Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2016 (actual)
- Primary completion
- Nov 2017 (actual)
- Study completion
- Nov 2017 (actual)
- First posted
- 22 Jul 2016 (estimated)
- Results
- Posted 5 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open Label | Experimental | Drug: MYK-461MYK-461 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MYK-461 | Drug | Open Label |
Primary outcome
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.
8 secondary outcomes
Number of Participants Achieving a Post-exercise Peak LVOT Gradient Response of < 30 mmHg. Gradient < 30 mmHg
Time frame: Baseline and Week 12
Change in Dyspnea Symptom Score From Baseline to Week 12
Time frame: Baseline and Week 12
Change in Peak VO2 From Baseline to Week 12
Time frame: Baseline and Week 12
Change in VE/VCO2 From Baseline to Week 12
Time frame: Baseline and Week 12
Change in Resting LVEF From Baseline to Week 12
Time frame: Baseline and Week 12
Change in LV Fractional Shortening (LVFS) From Baseline to Week 12
Time frame: Baseline and Week 12
Change in Global Longitudinal Strain (GLS) From Baseline to Week 12
Time frame: Baseline and Week 12
Change in Post-exercise Peak LVOT Gradient From Week 12 to Week 16
Time frame: Weeks 12 and 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31035291Heitner 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.
Related trials for Cardiomyopathy, Hypertrophic Obstructive
RecruitingPhase 2
A Trial to Evaluate the Efficacy and Safety of Ninerafaxstat in Patients With Symptomatic Non-obstructive Hypertrophic Cardiomyopathy
Non-obstructive Hypertrophic Cardiomyopathy
Active, not recruitingPhase 3
A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy
Obstructive Hypertrophic Cardiomyopathy
Enrolling by invitationPhase 2/3
Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Aficamten in Adults With HCM
Symptomatic Hypertrophic Cardiomyopathy (HCM)
RecruitingObservational study
Hypertrophic Cardiomyopathy Registry, Biobank and Imaging Data Repository
Hypertrophic Cardiomyopathy, Hypertrophic Obstructive Cardiomyopathy
Not yet recruiting
Coronary Sinus Reducer Objective Impact on SymptoMs, Ischaemia and miCrovascular Resistance in Non-obstructive Hypertrophic CardioMyopathy
Hypertrophic Cardiomyopathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy Sehnert, MD study chair
MyoKardia, Inc.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MYK-461 in people with Cardiomyopathy, Hypertrophic Obstructive and Left Ventricular Outflow Tract Obstruction, run by MyoKardia, Inc. at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Post-exercise Peak LVOT Gradient From Baseline to Week 12 (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02842242, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2021.