Clinical trial • Phase III • Cardiology

MAVACAMTEN for Symptomatic Obstructive Hypertrophic Cardiomyopathy|Hypertrophic obstructive cardiomyopathy

Phase III trial of MAVACAMTEN for Symptomatic Obstructive Hypertrophic Cardiomyopathy|Hypertrophic obstructive cardiomyopathy.

Overview

Trial Therapeutic Area
Cardiology
Trial Disease
Symptomatic Obstructive Hypertrophic Cardiomyopathy|Hypertrophic obstructive cardiomyopathy
Trial Stage
Phase III
Drug Modality
Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
15-01-2024
First CTIS Authorization Date
25-04-2024

Trial design

Randomised, placebo ("myk-461 capsules, placebo is a solid oral dosage form in size 2 gelatin capsules each containing 120 mg of an excipient blend. it is intended as a placebo to match myk-461 capsules of all active strengths")-controlled Phase III trial in Germany, Italy, Spain and others.

Randomised
Yes
Comparator
Placebo ("myk-461 capsules, placebo is a solid oral dosage form in size 2 gelatin capsules each containing 120 mg of an excipient blend. it is intended as a placebo to match myk-461 capsules of all active strengths")
Target Sample Size
29
Trial Duration For Participant
196

Eligibility

Recruits 29 paediatric patients.

Vulnerable Population
Adolescents (12 to <18 years) are included and flagged as a vulnerable population. Age-specific assent and consent documents are provided (assent forms for 12–15 and 16–17 year olds, parent/guardian informed consent forms, ICFs for adolescents reaching the age of majority). Separate patient/parent information brochures and assent guides are available.

Inclusion criteria

  • {"criterion_text":"- Adolescents aged 12 to <18 at the time of agreeing to participate"}
  • {"criterion_text":"- Diagnosis of HCM"}
  • {"criterion_text":"- Presence of LVOT obstruction"}
  • {"criterion_text":"- Presence of symptoms"}

Exclusion criteria

  • {"criterion_text":"- Phenocopy diseases resulting in myocardial hypertrophy not related to sarcomere dysfunction"}
  • {"criterion_text":"- Evidence of LVEF <50% in prior 6 months"}
  • {"criterion_text":"- Planned escalation in HCM therapy or upcoming intervention (eg, major cardiac surgery, HCM medication dose increase)"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Change from baseline in Valsalva LVOT gradient at Week 28","definition_or_measurement_approach":"Change from baseline measured as Valsalva left ventricular outflow tract (LVOT) gradient assessed at Week 28."}

Secondary endpoints

  • {"endpoint_text":"- Change from baseline in the following at Week 28: 1) Resting LVOT gradient 2) Post-exercise peak LVOT gradient 3) Maximal wall thickness 4) Ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e’)","definition_or_measurement_approach":"Change from baseline for each listed echocardiographic parameter assessed at Week 28."}
  • {"endpoint_text":"- Proportion of participants achieving an increase from baseline to Week 28 in peak oxygen uptake test (pVO2)","definition_or_measurement_approach":"Proportion achieving increase in peak oxygen uptake (pVO2) measured by exercise testing at Week 28 compared to baseline."}
  • {"endpoint_text":"- Proportion of participants achieving a reduction from baseline to Week 28 in maximal LVOT gradient to < 30 mmHg","definition_or_measurement_approach":"Proportion with maximal LVOT gradient reduced to <30 mmHg at Week 28 compared to baseline."}
  • {"endpoint_text":"- Proportion of participants with at least 1 class improvement in New York Heart Association (NYHA) class from baseline to Week 28","definition_or_measurement_approach":"Proportion with ≥1 class improvement in NYHA functional class at Week 28 versus baseline."}
  • {"endpoint_text":"- Proportion of participants with at least 1 grade improvement in mitral regurgitation at Week 28 Incidence of treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs)","definition_or_measurement_approach":"Proportion with ≥1 grade improvement in mitral regurgitation at Week 28; incidence of TEAEs and TESAEs collected during the treatment period."}
  • {"endpoint_text":"- Change from baseline in QT interval on electrocardiogram at Week 28","definition_or_measurement_approach":"Change from baseline in ECG QT interval measured at Week 28."}
  • {"endpoint_text":"- Incidence of left ventricular ejection fraction (LVEF) ≤ 30%","definition_or_measurement_approach":"Incidence of participants with LVEF ≤30% recorded during study assessments."}
  • {"endpoint_text":"- Incidence of LVEF < 50%","definition_or_measurement_approach":"Incidence of participants with LVEF <50% recorded during study assessments."}
  • {"endpoint_text":"- Summary of plasma concentrations by visit (Ctrough and post dose)","definition_or_measurement_approach":"Plasma concentration summaries (Ctrough and post-dose) by visit."}
  • {"endpoint_text":"- Cmax and AUC using sparse sampling utilizing population PK approach","definition_or_measurement_approach":"Estimation of Cmax and AUC using sparse sampling and population pharmacokinetic (PK) modelling approach."}
  • {"endpoint_text":"- Proportion of participants who evaluate taste and swallowability as neutral or better using taste and swallowability scales at Day 1 and Week 11","definition_or_measurement_approach":"Proportion rating taste and swallowability as neutral or better on specified scales at Day 1 and Week 11."}
  • {"endpoint_text":"- Change from baseline in the HCMSQ SoB domain at Week 28","definition_or_measurement_approach":"Change from baseline in the Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ) Shortness of Breath domain at Week 28."}

Recruitment

Planned Sample Size
29
Recruitment Window Months
60
Consent Approach
Informed consent obtained from parent(s)/guardian(s) with age-specific assent from adolescent participants. Age-specific forms include assent for 12–15 and 16–17 year olds, parent/guardian main ICFs, and ICFs for adolescents reaching the age of majority. Recruitment and participant information materials are provided in multiple languages as per submitted documents (English, German, French, Spanish, Italian as evidenced by available patient-facing documents).

Methods

  • Use of recruitment materials including patient flyers and parent information brochures (K2 recruitment materials) and patient assent guides directed at adolescents and parents/guardians; local site-based recruitment at participating paediatric cardiology centres (sites have provided K1/K2 recruitment documents).

Geography

Total Number Of Sites
8
Total Number Of Participants
11

Germany

Earliest CTIS Part Ii Submission Date
02-04-2024
Latest Decision Or Authorization Date
01-10-2025
Processing Time Days
548
Number Of Sites
2
Number Of Participants
2

Sites

Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
DHZC; Klinik für angeborene Herzfehler/Kinderkardiologie
Contact Person Name
Katja Weiss
Contact Person Email
katja.weiss@charite.de
Site Name
Deutsches Herzzentrum Muenchen Des Freistaates Bayern Klinik An Der Technischen Universitaet Muenchen
Department Name
Department of Congenital Heart Defects and Pediatric Cardiology
Contact Person Name
Cordula Maria Wolf
Contact Person Email
wolf@dhm.mhn.de

Italy

Earliest CTIS Part Ii Submission Date
29-01-2024
Latest Decision Or Authorization Date
07-11-2025
Processing Time Days
648
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
Azienda Ospedaliera Universitaria Meyer IRCCS
Department Name
Experimental and Clinical Medicine, UNIFI and Pediatric and Transistion
Contact Person Name
Iacopo Olivotto
Contact Person Email
Iacopo.olivotto@unifi.it

Spain

Earliest CTIS Part Ii Submission Date
04-04-2024
Latest Decision Or Authorization Date
03-10-2025
Processing Time Days
548
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
Hospital Universitario La Paz
Department Name
Pediatric Cardiology
Contact Person Name
Marta Gambra Arzoz
Site Name
Sant Joan De Deu Barcelona Hospital
Department Name
Cardiology
Contact Person Name
Georgia Sarquella Brugada
Contact Person Email
georgia.sarquella@sjd.es

Ireland

Earliest CTIS Part Ii Submission Date
19-03-2024
Latest Decision Or Authorization Date
03-11-2025
Processing Time Days
595
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Children's Health Ireland
Department Name
Cardiology
Contact Person Name
Terence Prendiville

France

Earliest CTIS Part Ii Submission Date
25-04-2024
Latest Decision Or Authorization Date
03-10-2025
Processing Time Days
527
Number Of Sites
2
Number Of Participants
2

Sites

Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Pediatric Neurometabolism
Contact Person Name
Xavier Iriart
Contact Person Email
xavier.iriart@chu-bordeaux.fr
Site Name
Hopital Necker Enfants Malades
Department Name
Cardiologie pédiatrique
Contact Person Name
Damien Bonnet
Contact Person Email
Damien.bonnet@aphp.fr

Sponsor

Primary sponsor

Full Name
Bristol-Myers Squibb Services Unlimited Company
Organisation Type
Pharmaceutical company
Country Of Registered Address
Ireland

Contract research organisations

Name
Iqvia Inc.
Responsibilities
Site Payments
Name
Fortrea Inc.
Responsibilities
Operational support including exporting/importing of biological samples and kit logistics

Third parties

  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Routine clinical pathology testing, Clinical chemistry, Clinical haematology, Clinical microbiology","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Data management platform","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Cardiovascular And Metabolic Disease Research Institute","duties_or_roles":"CPET Analysis","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"India","full_name":"Accenture Solutions Private Limited","duties_or_roles":"Pharmacovigilance:Medical review, Cases Data Entry.; submission administrative support; Embarc operations","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Iqvia Inc.","duties_or_roles":"Site Payments","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"Core Technology Services","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Cleveland Clinic Foundation","duties_or_roles":"Medical image analysis/ review - X-ray, MRI, ultrasound, etc., ECHO Analysis","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"Licensing and translations services","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Signant Health LLC","duties_or_roles":"PRO/CoA","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Exporting of blood samples, importing of collection kits (additional operational and laboratory support functions)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Alturas Analytics Inc.","duties_or_roles":"Pharmacokinetic (PK) testing","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"Sample storage","organisation_type":"Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Routine clinical pathology testing, Clinical chemistry, Clinical haematology, Clinical microbiology","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Mavacamten
Active Substance
MAVACAMTEN
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised (prodAuthStatus=1)
Investigational Product Name
"myk-461 capsules, placebo is a solid oral dosage form in size 2 gelatin capsules each containing 120 mg of an excipient blend. it is intended as a placebo to match myk-461 capsules of all active strengths"
Modality
Other

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