Short and long-term Hemodynamic and Physiological Effects of Mavacamten in Obstructive Hypertrophic Cardiomyopathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Skane

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2026-06-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

to investigate acute, sub-acute and chronic hemodynamic and physiological effects of treatment with mavacamten in patients with oHCM using state-of-the art cardiovascular magnetic resonance (CMR) imaging.

Secondary objectives 1

1. To assess changes in tissue characteristics (LGE-extent, native T1, T2) and hemodyanmics (pressure-volume (P-V)-loops, 4d-flow) measured by CMR.

Conditions and MedDRA coding

Obstructive Hypertrophic Cardiomyopathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. The subject has given their written consent to participate in the trial.
2. Age ≥ 18 years
3. Diagnosis of oHCM with unexplained LV hypertrophy with nondilated ventricular chambers in the absence of other cardiac (eg, hypertension, aortic stenosis) or systemic disease and with maximal LV wall thickness ≥15 mm
4. Eligible for on-label mavacamten therapy per Swedish prescribing information.
5. Left ventricular outflow tract (LVOT) ≥ 50 mmHg at rest, during Valsalva or post-exercise.
6. Left ventricular ejection fraction ≥ 55%
7. New York Heart Association (NYHA) class II or III symptoms.
8. Participants who are capable of becoming pregnant must not be pregnant or lactating and, if sexually active, must use effective birth control methods (see section 7.4) from the Screening visit through 6 months after the last dose of mavacamten.

Exclusion criteria 20

1. Presence or planned implantation of electronic cardiac devices such as ICD or pacemaker
2. History of or planned septal reduction therapy (surgical myectomy or percutaneous alcohol ablation) during trial period
3. Known infiltrative or storage disorder causing cardiac hypertrophy that mimics oHCM, such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy
4. Has paroxysmal, intermittent atrial fibrillation with atrial fibrillation present per the investigator’s evaluation of the participant’s ECG at the time of Screening
5. Has permanent atrial fibrillation
6. Current treatment (within 14 days prior to screening) or planned treatment during the study with: (a) a strong CYP3A4 inhibitor in participants with poor or unknown CYP2C19 metaboliser phenotype; (b) the simultaneous combination of a strong CYP2C19 inhibitor and a strong CYP3A4 inhibitor; (c) strong inducers of both CYP2C19 and CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, efavirenz, St. John's Wort); or (d) omeprazole or esomeprazole.
7. Has documented obstructive coronary artery disease (>70% stenosis in one or more epicardial coronary arteries) or history of myocardial infarction
8. Has known moderate or severe (as per investigator’s judgment) aortic valve stenosis at Screening
9. Has any acute or serious comorbid condition (eg, major infection or hematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction) that, in the judgment of the investigator, could lead to premature termination of study participation or interfere with the measurement or interpretation of the efficacy and safety assessments in the study
10. Reduced kidney function with estimated GFR <30 ml/min/1.73m2
11. Severe impairment of liver function (Child-Pugh class C) or if there is an alanine aminotransferase or aspartate aminotransferase result, the value must be <3 × the upper limit of the laboratory reference range
12. Unable to comply with the study requirements
13. Unable to perform CMR exams
14. Body mass index ≥ 40kg/m2
15. Participation or recent participation in a clinical trial with an investigational medicinal product within 30 days.
16. Previous participation in this trial
17. Known or suspected allergies against any product included in the trial
18. Pregnancy (positive p-hCG test at screening), breastfeeding, or planned pregnancy
19. Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of participation in the trial
20. Treatment or disease which, according to the investigator, can affect treatment or trial results

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in myocardial perfusion reserve (MPR) (averaged values across all hypertrophied myocardial segments without significant LGE) from baseline to 2 years after initiation of treatment.

Secondary endpoints 7

1. Change in MPR from BL to 12 weeks
2. Change in MPR from BL to 1 year
3. Changes in T1, T2 and extracellular volume (ECV) mapping from BL to 12 w, 1 year and 2 years
4. Change in LGE extent from BL to 12 w, 1 year and 2 years
5. Change in stroke work, ventricular efficiency, contractility, and arterial elastance assessed by P-V-loop-analysis from BL to 12 w, 1 year and 2 years
6. Change in kinetic energy and regional pressure gradients assessed by 4D flow-analysis from BL to 12 w, 1 year and 2 years
7. Changes in myocardial mass and left atrial volume assessed by standard CMR from BL to 12 w, 1 year and 2 years

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Skane

Sponsor organisation

Region Skane

Address

Dockplatsen 26, Malmo S:t Petri Malmo S:t Petri

City

Malmo

Postcode

211 74

Country

Sweden

Scientific contact point

Organisation

Region Skane

Contact name

Oscar Braun

Public contact point

Organisation

Region Skane

Contact name

Oscar Braun

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

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

Documents 6 files

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

Application history

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