Biological Collection for the Purpose of Exploring Genetic and Clinical-biological Factors Associated With Variability in Response to Mavacamten in the Treatment of Obstructive Hypertrophic Cardiomyopathy

NCT07439952 | Not Yet Recruiting

• 2 other identifiers: APHP250667 -2025-A00838-41
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 3

Brief Summary

The European Medicines Agency has required pre-treatment genotyping of CYP2C19 to determine the initial and maximum dosage, in order to avoid overexposure to mavacamten associated with a decrease in ventricular ejection fraction below 50% in slow metabolisers of CYP2C19 (AUC multiplied by 3.4). The study is a requalification for the search for DNA samples obtained during treatment in order to genotype the genes of interest.The primary objective of the study is to estimate, for each of the CYP2C19 phenotypes of interest determined by genotyping (ultra-rapid, rapid, normal/extensive and intermediate metabolisers), the proportion of patients who are non-responders to mavacamten at each time point (D0, Week 4, Week 8, Week 12 and Week 24 in the treatment of HCM). This is a multicentre (3 centres which are hospitals of APHP) study aiming to include 300 patients with obstructive hypertrophic cardiomyopathy treated with Mavacamten who underwent or are undergoing CYP2C19 genotyping at the start of treatment. The inclusion period is 36 months and the follow-up period is 6 months. The total duration of the study is 42 months.

Conditions

Obstructive Hypertrophic Cardiomyopathy (oHCM)

Keywords

mavacamten; obstructive hypertrophic cardiomyopathy; polymorphisms of CYP2C19, CYP3A4/CYP3A5 and CYP2C9

Outcome Measures

Primary Outcomes (1)

• Response rate to Mavacamten treatment

  Proportion of patients responding to mavacamten (LVEF \>55% and LVOT gradient at Valsalva \<30 mL/min) according to different CYP2C19 and CYP3A phenotypic groups at 12 and 24 weeks, evaluated by echocardiography

  Day 0, Week4, Week 8, Week 12, Week 24

Secondary Outcomes (4)

• Response rate to Mavacamten treatment in the above-mentioned populations

  Day 0, Week4, Week 8, Week 12, Week 24

• Response rate to Mavacamten treatment in the general population and in the above-mentioned populations

  Day 0, Week4, Week 8, Week 12, Week 24

• Description of cardiac and other adverse effects (excluding reduced LVEF) in the general population and in the above-mentioned populations

  Day 0, Week4, Week 8, Week 12, Week 24

• Variation in dosage of Mavacamten at weeks 4, week 8, week 12 and week 24 according to the different populations

  Weeks 4, week 8, week 12 and week 24

Study Arms (1)

Patients with oHCM treated with Mavacamten who underwent or are undergoing CYP2C19 genotyping at

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

300 patients with obstructive hypertrophic cardiomyopathy treated with Mavacamten who underwent or are undergoing CYP2C19 genotyping at the start of treatment.

You may qualify if:

• \- Patients aged ≥18 years
• Diagnosis of obstructive hypertrophic cardiomyopathy (OHCM), based on the guidelines of the European Society of Cardiology (Arbelo et al. 2023), with unexplained left ventricular hypertrophy and a maximum LVOT gradient ≥ 50 mmHg at rest, or after Valsalva manoeuvre or exercise at the time of diagnosis, and an LVOT gradient with Valsalva manoeuvre ≥ 30 mmHg at selection
• With cardiac symptoms defined as NYHA class II/III, persistent despite background treatment (beta-blockers or calcium channel blockers)
• LVEF ≥55% at the start of treatment with mavacamten
• Initiation of treatment with mavacamten or patient already receiving treatment
• Prescription of pre-treatment CYP2C19 genotyping performed
• Consent to participate signed by the patient
• Beneficiary of health insurance

You may not qualify if:

• Minors
• Adults under guardianship (legal guardianship and curatorship) or judicial protection
• Pregnant or breastfeeding women

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (3)

APHP, Ambroise Paré

Boulogne-Billancourt, 92100, France

Location

APHP, Bicêtre hospital

Le Kremlin-Bicêtre, France

Location

APHP, La Pitié Salpetriere hospital

Paris, 75013, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

DNA from blood samples

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Central Study Contacts

Philippe CHARRON, Pr

CONTACT

+33 1 42 16 28 92; philippe.charron@aphp.fr

Céline Verstuyft, Pr

CONTACT

+3 1 45 21 27 21; celine.verstuyft@aphp.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2026
• First Posted: February 27, 2026
• Study Start: February 5, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: February 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)