Hypertrophic cardiomyopathy (HCM) Circulatory System
Conditions
Interventions
Phase 2a participants will all receive azacitidine treatment, with the dose being escalated/deescalated based on the TITE-CRM DLT model. During Phase 2b participants will be randomly assigned by 1:1 a
Sponsors
Belfast Health and Social Care Trust
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age 18 to 75 years who have a diagnosis of phenotype positive nHCM consistent with current American and European guidelines; Left ventricle (LV) wall thickness =15 mm (or =13 mm with a family history of HCM). 2. Symptomatic of nHCM at screening (defined as being NYHA functional class II/III). 3. Elevated N-terminal pro-hormone of Brain Natriuretic Peptide (NT pro-BNP) level >125 pg/ml as measured within 6 months of screening. 4. Left ventricular ejection fraction (LVEF) =55%. 5. Left Ventricular Outflow Tract (LVOT) peak gradient at rest and during Valsalva <50mmHg as determined by the echocardiography laboratory. 6. Men who are sexually active, must agree to acceptable birth control methods whilst receiving the the study drug and until 3 months after the last dose of study drug. 7. Women of childbearing potential, must agree to acceptable birth control methods during the study and until 6 months after the last dose of study drug.
Exclusion criteria
Exclusion criteria: 1. Presence of any active malignancy that required treatment within the last year 2. Patient is known to be pregnant or lactating 3. Consent to participate is declined 4. Absolute contraindication to study drug 5. NYHA functional class IV 6. Patients with reduced baseline blood counts (i.e. WBC <3.0 × 109/L or ANC <1.5 × 109/L or platelets <75.0 × 109/L) prior to the first treatment 7. Patient is enrolled in another investigational drug study within the past 6 months 8. Patient is incapable of completing exercise stress test
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 2a: Safety of azacitidine, as defined by the incidence of dose-limiting toxicity (DLT) in each cohort. Adverse events will be monitored on days 8, 15, 22, 29, 43, 57, 71, 85, 99, 113 and at follow up on day 141. Phase 2b: Peak oxygen consumption (pVO2) measured by CPET at baseline (day 0) and following 16 weeks treatment (day 141). | — |
Secondary
| Measure | Time frame |
|---|---|
| All measured at baseline (day 0) and at 16 weeks (day 113): Phase 2a: 1. The optimal dose of azacitidine for use in Phase 2b of the clinical trial 2. Patient functional class measured using the New York Heart Association functional classification of heart failure (NYHA) at baseline and following 16 weeks treatment with azacitidine 3. Quality of life measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ) quality of life assessment tool at baseline and following 16 weeks treatment with azacitidine 4. Blood biomarkers including cardiac Troponin T and NT-proBNP measured using laboratory analysis at baseline and following 16 weeks treatment with azacitidine 5. Exercise tolerance measured by 6-minute walk test from baseline to week 16 6. Peak oxygen consumption (pVO2) measured by cardiopulmonary exercise testing (CPET) from baseline to week 16 7. Echocardiographic parameters of left ventricular function measured at baseline and following 16 weeks treatment with azacitidine 8. Cardiac MRI parameters of left ventricular function and late gadolinium enhancement measured at baseline and following 16 weeks treatment with azacitidine Phase 2b: 1. Patient functional class measured using NYHA symptom class at baseline and following 16 weeks treatment with azacitidine 2. Quality of life measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ) quality of life assessment tool at baseline and following 16 weeks treatment with azacitidine) 3. Blood biomarkers including cTnT and NT-proBNP measured using laboratory analysis at baseline and following treatment with azacitidine 4. Exercise tolerance measured by 6-minute walk test at baseline and following 16 weeks treatment with azacitidine 5. Echocardiographic imaging parameters including systolic and diastolic function and global longitudinal strain measured at baseline and following 16 weeks treatment with azacitidine 6. Cardiac MRI parameters including systolic and diastolic function and late gadolinium enhan | — |
Countries
Northern Ireland, United Kingdom
Outcome results
None listed