A Study of Mavacamten in Adolescent Participants with Symptomatic Obstructive Hypertrophic Cardiomyopathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bristol-Myers Squibb Services Unlimited Company

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

27 Aug 2024 → ongoing

Decision date (initial)

2024-05-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bristol-Myers Squibb Unlimited Company

External identifiers

EU CT number

2023-505650-17-00

WHO UTN

U1111-1290-1175

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

To evaluate the effect of mavacamten compared to placebo on left ventricular outflow tract (LVOT) obstruction in adolescents with symptomatic obstructive HCM

Secondary objectives 5

1. To evaluate the effect of mavacamten compared to placebo on other clinically meaningful aspects of disease (eg, symptom status, other echocardiographic parameters) in adolescents with symptomatic obstructive HCM
2. To evaluate the safety and tolerability of mavacamten in adolescents with symptomatic obstructive HCM
3. To assess the pharmacokinetics (PK) of mavacamten in adolescents with symptomatic obstructive HCM
4. To evaluate taste and swallowability of mavacamten capsules in adolescents with symptomatic obstructive HCM after first and multiple doses
5. To evaluate the effect of mavacamten on patient-reported symptoms

Conditions and MedDRA coding

Symptomatic Obstructive Hypertrophic Cardiomyopathy

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002231-PIP01-17

Plan to share IPD

Yes

IPD plan description

BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Adolescents aged 12 to <18 at the time of agreeing to participate
2. Diagnosis of HCM
3. Presence of LVOT obstruction
4. Presence of symptoms

Exclusion criteria 3

1. Phenocopy diseases resulting in myocardial hypertrophy not related to sarcomere dysfunction
2. Evidence of LVEF <50% in prior 6 months
3. Planned escalation in HCM therapy or upcoming intervention (eg, major cardiac surgery, HCM medication dose increase)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in Valsalva LVOT gradient at Week 28

Secondary endpoints 12

1. 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’)
2. Proportion of participants achieving an increase from baseline to Week 28 in peak oxygen uptake test (pVO2)
3. Proportion of participants achieving a reduction from baseline to Week 28 in maximal LVOT gradient to < 30 mmHg
4. Proportion of participants with at least 1 class improvement in New York Heart Association (NYHA) class from baseline to Week 28
5. 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)
6. Change from baseline in QT interval on electrocardiogram at Week 28
7. Incidence of left ventricular ejection fraction (LVEF) ≤ 30%
8. Incidence of LVEF < 50%
9. Summary of plasma concentrations by visit (Ctrough and post dose)
10. Cmax and AUC using sparse sampling utilizing population PK approach
11. Proportion of participants who evaluate taste and swallowability as neutral or better using taste and swallowability scales at Day 1 and Week 11
12. Change from baseline in the HCMSQ SoB domain at Week 28

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bristol-Myers Squibb Services Unlimited Company

Sponsor organisation

Bristol-Myers Squibb Services Unlimited Company

Address

Plaza 254 Blanchardstown Corporate Park 2, Ballycoolin Ballycoolin

City

Dublin 15

Postcode

D15 T867

Country

Ireland

Scientific contact point

Organisation

Bristol-Myers Squibb Services Unlimited Company

Contact name

GSM-CT

Public contact point

Organisation

Bristol-Myers Squibb Services Unlimited Company

Contact name

GSM-CT

Third parties 15

Locations

5 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 67 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications