|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Hypertrophic Cardiomyopathy (HCM)
|Medical condition in easily understood language
|HCM is a heart condition that leads to the thickening and scarring of the walls of the heart.
|Diseases [C] - Cardiovascular Diseases [C14]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10010331 - Congenital, familial and genetic disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To find out if trientine reduces heart muscle thickening in patients with hypertrophic cardiomyopathy.
|Secondary objectives of the trial
|To find out if trientine improves exercise capacity, improves heart function and reduces abnormal heart rhythms in patients with hypertrophic cardiomyopathy. The study will also assess how trientine works in hypertrophic cardiomyopathy.
|Trial contains a sub-study
|Principal inclusion criteria
|1. Written informed consent.
2. Age 18-70 inclusive.
3. Hypertrophic cardiomyopathy (HCM), as defined by the European Society of Cardiology HCM guidelines as: “a wall thickness ≥15 mm in one or more LV myocardial segments that is not explained solely by loading conditions”. The same definition is applied to first-degree relatives of patients with HCM i.e. all participants are required to have a LV wall thickness ≥15 mm. Wall thickness is as measured on the most recent cardiovascular magnetic resonance (CMR) scan performed prior to the baseline visit. If CMR has not been performed previously, wall thickness measurement should be taken from the most recent echocardiogram performed prior to the baseline visit .
(It is recognised that in the European Society of Cardiology guidelines a clinical diagnosis of HCM in first-degree relatives requires a wall thickness that is less than this value, however ≥15 mm is applied here in order to ensure that all participants have an unequivocal phenotype).
4. New York Heart Association class I, II or III at the most recent clinical assessment performed prior to the baseline visit.
|Principal exclusion criteria
|1. Previous or planned septal reduction therapy.
2. Previously documented myocardial infarction or severe coronary artery disease.
3. Uncontrolled hypertension, defined as a systolic blood pressure of >180mmHg or a diastolic blood pressure of > 100mmHg at Visit 1.
4. Known LV EF < 50%, as measured on the most recent CMR scan performed prior to the baseline visit. If CMR has not been performed previously, the most recent echocardiogram performed prior to the baseline visit should be used.
5. Previously documented persistent atrial fibrillation.
6. Anaemia, defined as haemoglobin being below the local site normal reference range, at Visit 1.
7. Iron deficiency, defined as serum iron being below the local site normal reference range, at Visit 1.
8. Copper deficiency, defined as serum copper being below the normal reference range, at Visit 1.
9. Pacemaker or implantable cardioverter defibrillator.
10. Known severe valvular heart disease, as demonstrated on the most recent heart imaging performed prior to the baseline visit.
11. Previously documented other cardiomyopathic cause of myocardial hypertrophy (e.g. amyloidosis, Fabry disease, mitochondrial disease).
12. History of hypersensitivity to any of the components of the investigational medicinal product (IMP).
13. Known contraindication to MRI scanning.
14. Pregnancy, lactation or planning pregnancy. Women of childbearing capacity are required to have a negative serum pregnancy test before treatment , must agree to pregnancy tests at study visits as defined in the Section 8 and must agree to maintain highly effective contraception as defined in Section 8 during the study.
15. Any medical condition, which in the opinion of the Investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.
|E.5 End points
|Primary end point(s)
|Change in LVMi (g/m2), measured using CMR.
|Timepoint(s) of evaluation of this end point
|Measured from baseline to week 52.
|Secondary end point(s)
|1. Cumulative urine copper excretion, measured using urinary copper.
2. Change in exercise capacity, measured using cardiopulmonary exercise testing (CPET).
3. Change in number of non-sinus supraventricular heart beats, presence and amount of atrial fibrillation, number of ventricular-origin beats and presence and amount of non-sustained ventricular tachycardia, in 24 hours, measured using ambulatory heart monitoring.
4. Change in circulating high sensitivity troponin.
5. Change in LV global longitudinal strain and strain rate, wall thickness, mass, volumes and ejection fraction (EF) measured using CMR.
6. Change in peak left ventricular outflow tract gradient, measured using CMR.
7. Change in atrial volume and function, measured using CMR.
|Timepoint(s) of evaluation of this end point
|All assessed from baseline to week 52, except urine copper excretion, which is assessed from baseline to weeks 13, 26, 39 and 52.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|The end of the trial is defined to be the date on which data for all participants is locked and data entry privileges are withdrawn from the trial database.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days