Clinical Trials Register

Summary
EudraCT Number:	2021-005329-26
Sponsor's Protocol Code Number:	CV027-031
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-11-01
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2021-005329-26

A.3

Full title of the trial

A Randomized, Double-blind, Placebo-controlled Clinical Study to Evaluate Mavacamten in Adults with Symptomatic Nonobstructive Hypertrophic Cardiomyopathy

Estudio clínico aleatorizado, doble ciego y controlado con placebo para evaluar mavacamten en adultos con cardiomiopatía hipertrófica sintomática no obstructiva

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Randomized, Double-blind, Placebo-controlled Clinical Study to Evaluate Mavacamten in Adults with Cardiomyopathy

Estudio clínico aleatorizado, doble ciego y controlado con placebo para evaluar mavacamten en adultos con cardiomiopatía

A.3.2

Name or abbreviated title of the trial where available

Mavacamten in nonobstructive HCM

Mavacamten en CMH no obstructiva

A.4.1

Sponsor's protocol code number

CV027-031

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1269-8581

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Myokardia, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Myokardia, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bristol-Myers Squibb International Corporation
B.5.2	Functional name of contact point	Head of the GSM-CT
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'Alliance - Avenue de Finlande, 4
B.5.3.2	Town/ city	Braine-l'Alleud
B.5.3.3	Post code	1420
B.5.3.4	Country	Belgium
B.5.4	Telephone number	900 150 160
B.5.6	E-mail	clinical.trials@bms.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Mavacamten
D.3.2	Product code	MYK-461
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	MYK-461
D.3.9.3	Other descriptive name	MAVACAMTEN
D.3.9.4	EV Substance Code	SUB191202
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Mavacamten
D.3.2	Product code	MYK-461
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	MYK-461
D.3.9.3	Other descriptive name	MAVACAMTEN
D.3.9.4	EV Substance Code	SUB191202
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Mavacamten
D.3.2	Product code	MYK-461
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	MYK-461
D.3.9.3	Other descriptive name	MAVACAMTEN
D.3.9.4	EV Substance Code	SUB191202
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Mavacamten
D.3.2	Product code	MYK-461
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	MYK-461
D.3.9.3	Other descriptive name	MAVACAMTEN
D.3.9.4	EV Substance Code	SUB191202
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Mavacamten
D.3.2	Product code	MYK-461
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	MYK-461
D.3.9.3	Other descriptive name	MAVACAMTEN
D.3.9.4	EV Substance Code	SUB191202
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Symptomatic Nonobstructive Hypertrophic Cardiomyopathy

cardiomiopatía hipertrófica sintomática no obstructiva

E.1.1.1

Medical condition in easily understood language

Symptomatic hardening of the left ventricle.

Solidificación Sintomática del ventrículo izquierdo

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10049813
E.1.2	Term	Non-obstructive cardiomyopathy
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10020871
E.1.2	Term	Hypertrophic cardiomyopathy
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy of a 52-week course of
mavacamten compared to placebo on patient reported health status

To assess the efficacy of a 52-week course of
mavacamten compared to placebo on exercise
capacity

Evaluar la eficacia de un ciclo de 52 semanas de mavacamten en comparación con placebo en el estado de salud notificado por el paciente

Evaluar la eficacia de un ciclo de 52 semanas de mavacamten en comparación con placebo en la capacidad para hacer ejercicio

E.2.2

Secondary objectives of the trial

Evaluate the effects of mavacamten on exercise capacity as measured by VE/VCO2

Evaluate the effects of mavacamten on NYHA classification

Evaluate the effects of mavacamten on the composite of NYHA and pVO2

Evaluate the effects of mavacamten on cardiac biomarkers

Evaluate the effects of mavacamten on patient reported shortness of breath

Evaluate the effects of mavacamten on composite of cardiovascular events

Evaluar los efectos de mavacamten sobre la capacidad para hacer ejercicio medida mediante VE/VCO2

Evaluar los efectos de mavacamten en la clasificación de la NYHA

Evaluar los efectos de mavacamten en el criterio combinado de NYHA y pVO2

Evaluar los efectos de mavacamten sobre los biomarcadores cardíacos

Evaluar los efectos de mavacamten en la disnea notificada por el paciente

Evaluar los efectos de mavacamten en el criterio combinado de acontecimientos cardiovasculares

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Cardiac magnetic resonance (CMR) imaging sub-study (80 participants)
•Primary endpoint: change in measures of LV mass index
•Exploratory endpoints: changes in myocardial fibrosis
•CMR will be done at randomization and at week 52

Incidence of cardiac arrhythmias sub-study (~80 participants)
•Sub-study endpoint: Incidence of AF, ventricular tachycardia, ventricular fibrillation, and conduction abnormalities including heart block from baseline to 52 weeks
•A wearable electrocardiogram (ECG) monitor will be applied 10 times during the study as per the Schedule of Activities

Subestudio de imágenes por resonancia magnética cardíaca (CMR) (80 participantes)
•Criterio de valoración primario: cambio en las medidas del índice de masa del VI
•Criterios de valoración exploratorios: cambios en la fibrosis miocárdica
•La CMR se realizará en la aleatorización y en la semana 52

Subestudio de incidencia de arritmias cardíacas (~80 participantes)
•Criterio de valoración del subestudio: Incidencia de FA, taquicardia ventricular, fibrilación ventricular y anomalías de la conducción, incluido el bloqueo de corazón desde el inicio hasta las 52 semanas
•Se aplicará un monitor de electrocardiograma (ECG) portátil 10 veces durante el estudio según el Calendario de Actividades

E.3

Principal inclusion criteria

1. Participants must be 18 years old or local age of majority at the time of signing the informed consent
2. Female participants must adhere to highly effective contraceptive methods or have documented proof that they are not of childbearing potential
3. No additional contraceptive measures are required to be used for male participants
4. Diagnosis of HCM consistent with current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines.
5. Peak LVOT pressure gradient < 30 mmHg at rest and < 50 mmHg with provocation (Valsalva maneuver and stress echocardiography)
6. CPET: Documented oxygen saturation at rest >90% at Screening. Able to perform an upright cardiopulmonary stress test (CPET) and has a respiratory exchange ratio (RER) ≥ 1.0 at Screening per central reading. If the RER is between 0.91 and 1.0, the participant may be enrolled if the central CPET laboratory determines that peak exercise has been achieved. Participants with subpeak performance may not be enrolled as described in the CPET Laboratory Manual.
7. New York Heart Association (NYHA) Class II or III
8. NT-proBNP≥200 pg/mL or BNP≥70 pg/mL
9. LVEF ≥60 % as determined by the echocardiography central laboratory

1. Los participantes deben tener cumplidos los 18 años o ser mayores de edad, según la normativa nacional, en el momento de firmar el consentimiento informado
2. Las participantes femeninas deben adherirse a un sistema altamente efectivo de método anticonceptivo o disponer de pruebas documentadas de que no tienen capacidad de quedarse embarazadas
3. No se requieren medidas anticonceptivas adicionales en el caso de los participantes varones
4. Diagnóstico de MCH concordante con las directrices actuales de la American College of Cardiology Foundation [Fundación del Colegio Estadounidense de Cardiología]/American Heart Association [Asociación Estadounidense de Cardiología] y la European Society of Cardiology [Sociedad Europea de Cardiología]
5. Gradiente de presión máxima del infundíbulo ventricular izquierdo <30 mmHg en reposo y <50 mmHg con provocación (maniobra de Valsalva y ecocardiografía de esfuerzo)
6. Prueba de ejercicio cardiopulmonar (PECP): Saturación de oxígeno documentada en reposo >90 % en la selección. El participante puede realizar una PECP en posición vertical y tiene un cociente respiratorio (CR) ≥1,0 en la selección según la lectura central. Si el CR está entre 0,91 y 1,0, se podrá inscribir al participante si el laboratorio central encargado de la PECP determina que se ha alcanzado el máximo ejercicio. Los participantes que presenten un rendimiento inferior al pico no pueden inscribirse para las afecciones descritas en el manual de laboratorio de la PECP
7. Clase II o III de la New York Heart Association (Asociación de Cardiología de Nueva York [NYHA])
8. NT-proBNP ≥200 pg/ml o BNP ≥70 pg/ml
9. FEVI ≥60 % según lo determinado por la ecocardiografía del laboratorio central

E.4

Principal exclusion criteria

Medical Conditions
- Known infiltrative or storage disorder causing cardiac hypertrophy that mimics nHCM such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy
- History of unexplained syncope within 6 months prior to screening
- History of sustained ventricular tachyarrhythmia (> 30 seconds) within 6 months prior to Screening
- Paroxysmal or persistent (non-permanent) AF detected at the time of screening. Permanent AF or history of paroxysmal or persistent AF is allowed if the participant is anticoagulated and the investigator considers the heart rate adequately controlled
- CV diseases or treatments that in the opinion of the investigator increase the unpredictability of or change the participants’ clinical course.
- Acute heart failure from 4 weeks prior to screening up to randomization
- Myocardial infarction (increase in cardiac enzymes in combination with symptoms of ischemia or new ischemic ECG changes), coronary artery bypass graft surgery, or other major CV surgery, stroke, or transient ischemic attack in the past 90 days
- Women who are breastfeeding or pregnant.

Prior/Concomitant Therapy
- Any adjustments of beta-blockers, verapamil, or diltiazem within 2 weeks prior to Screening and up to the day of randomization
- Concomitant use of strong inhibitors of cytochrome P450 (CYP) 2C19

Other Exclusion Criteria
- Any other serious condition that in the opinion of the investigator could prevent participation in the study and follow-up
- Completed a study with an investigational device or drug < 30 days or 5 half-lives prior to screening
- Participants who have completed a study with mavacamten or aficamten

Condiciones medicas
• Trastorno infiltrativo o del almacenamiento conocido que cause hipertrofia cardíaca que imita a la MCHn, como enfermedad de Fabry, amiloidosis o síndrome de Noonan con hipertrofia del VI
• Antecedentes de síncope de filiación desconocida en los 6 meses anteriores a la selección
• Antecedentes de taquiarritmia ventricular sostenida (>30 segundos) en los 6 meses anteriores a la selección
• FA paroxística o persistente (no permanente) detectada en el momento de la selección. Se permite la FA permanente o los antecedentes de FA paroxística o persistente si el participante está anticoagulado y el investigador considera que la frecuencia cardíaca está corregida adecuadamente
• Enfermedades o tratamientos CV que, en opinión del investigador, aumenten la imprevisibilidad de la evolución clínica de los participantes o modifiquen dicha evolución
• Insuficiencia cardíaca aguda desde 4 semanas antes de la selección hasta la aleatorización
• Infarto de miocardio (aumento de las enzimas cardíacas en combinación con síntomas de isquemia o nuevos cambios isquémicos en el ECG), operación de injerto de derivación de arteria coronaria u otra intervención de cirugía CV mayor, accidente cerebrovascular o accidente isquémico transitorio en los últimos 90 días
• Mujeres en período de lactancia o Embarazadas.

Tratamientos previos o simultáneos
• Cualquier ajuste en los betabloqueantes, el verapamilo o el diltiazem en las 2 semanas anteriores a la selección y hasta el día de la aleatorización
• Uso simultáneo de inhibidores potentes del citocromo P450 (CYP) 2C19.

Otros criterios de exclusión
• Cualquier otra afección grave que, en opinión del investigador, pueda impedir la participación en el estudio y el seguimiento
• Finalización por parte del candidato de un estudio llevado a cabo con un producto sanitario o fármaco en investigación <30 días o 5 semividas antes de la selección
• Finalización por parte del candidato de un estudio con mavacamten o aficamten

E.5 End points

E.5.1

Primary end point(s)

1. Change from baseline in KCCQ CSS
2. Change from baseline in pVO2

1. Cambio desde el inicio en CSS del cuestionario KCCQ
2. Cambio desde el inicio en pVO2

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Week 52
2. Week 52

1. semana 52
2. semana 52

E.5.2

Secondary end point(s)

1. Change from baseline in VE/VCO2 slope
2. Proportion of participants with at least 1 class of NYHA improvement from baseline
3. Proportion of participants with (1) pVO2 ≥ 1.5 mL/kg/min and NYHA improvement ≥ 1 from baseline ; or (2) pVO2 ≥ 3 mL/kg/min and NYHA no worsening from baseline
4. Change from baseline in NT-pro BNP
5. Change from baseline in cTn-T
6. Change from baseline in HCMSQ-SoB domain
7. First MACE-Plus events defined as any CV death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, or hospitalization for arrhythmias

1. Cambio desde el inicio en la pendiente de EV/VCO2
2. Proporción de participantes con mejoría de al menos 1 clase en la clasificación de la NYHA desde el inicio.
3. Proporción de participantes con (1) pVO2 ≥1,5 ml/kg/min y mejoría en la clasificación NYHA
≥1; o (2) pVO2 ≥3 ml/kg/min y clasificación NYHA sin empeoramiento desde el inicio.
4. Cambio desde el inicio en el valor de NT-proBNP
5. Cambio desde el inicio en el valor de cTn-T
6. Cambio desde el inicio en el cuestionario HCMSQ-SoB
7. Los primeros acontecimientos cardiovasculares mayores (MACE-plus) se definen como cualquier muerte por causas CV, infarto de miocardio no mortal, accidente cerebrovascular no mortal, hospitalización por insuficiencia cardíaca u hospitalización por arritmias

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Week 52
2. Week 52
3. Week 52
4. Week 52
5. Week 52
6. Week 52
7. From the study drug initiation to occurrence of the first MACE-Plus or when the last subject reaches Week 52

1. semana 52
2. semana 52
3. semana 52
4. semana 52
5. semana 52
6. semana 52
7. Desde el inicio del fármaco del estudio hasta la aparición del primer MACE-Plus o cuando el último sujeto llega a la semana 52

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Biomarkers

Biomarcadores

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Brazil

Canada

Israel

Japan

Korea, Republic of

United States

Austria

France

Poland

Netherlands

Spain

Czechia

Germany

Italy

Belgium

Denmark

Hungary

Norway

Portugal

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

UVUP

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

400

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

224

F.4.2.2

In the whole clinical trial

420

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

At the conclusion of the study, if the study treatment is not available as an approved and available treatment, study intervention will be provided via an extension of the study, a rollover study requiring approval by the responsible Health Authority and ethics committee, or through another mechanism at the discretion of BMS.

Al final del estudio, si el tratamiento del estudio no está disponible como un tratamiento aprobado y disponible, la intervención del estudio se proporcionará a través de una extensión del estudio, un estudio de rollover que requiere la aprobación de la Autoridad de Salud responsable y el comité de ética, o a través de otro mecanismo a discreción de BMS.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2023-01-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-12-21

P. End of Trial
P.	End of Trial Status	Ongoing

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