Study of Efficacy of Oral Sacubitril/Valsartan in Adult Patients With Non-obstructive Hypertrophic Cardiomyopathy

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if LCZ696 is safe, tolerable and can improve exercise capacity (via improved peak VO2) in non-obstructive HCM patient population over the course of 50 weeks of treatment.

Official Title
-----------------
A Multi-center, Randomized, Placebo-controlled Patient and Investigator-blinded Study to Explore the Efficacy of Oral Sacubitril/Valsartan in Adult Patients With Non-obstructive Hypertrophic Cardiomyopathy (nHCM)

Conditions
-----------------
Cardiomyopathy, Hypertrophic

Intervention / Treatment
-----------------
* Drug: LCZ696
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed with Hypertrophic Cardiomyopathy with a left ventricular wall thickness greater than or equal to 13mm as determined by the echocardiogram obtained during the screening/baseline period Left ventricular ejection fraction (LVEF) greater than or equal to 50% as determined by echocardiogram obtained during the screening/baseline period Symptoms consistent with New York Heart Association (NYHA) Class II-III heart failure by physician assessment, or asymptomatic/NYHA Class I patients with: NT-proBNP blood sample levels above 250 pg/ml and peak VO2 of less than or equal to 80% of predicted based on age and gender as determined by cardiopulmonary exercise testing Exclusion Criteria: Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for ≥7 days after stopping study drug Patients with a resting or provokable left ventricular outflow tract gradient of greater than or equal to 30mm Hg Septal reduction procedure within 3 months of the screening/baseline visit History of atrial fibrillation within 6 months of the screening/baseline visit or placement of ICD for secondary prevention Patients with a peak VO2 on the screening/baseline cardiopulmonary exercise test of > 80% of predicted based on age and gender Patients who require treatment with ACE inhibitors, angiotensin receptor blockers (ARBs), or renin inhibitors Known infiltrative or storage disorder such as Fabry disease, or amyloidosis Known or suspected symptomatic coronary artery diseases or evidence of prior myocardial infarction Systolic blood pressure of <100 mmHg or symptomatic hypotension during the screening/baseline period or treatment run-in period Contraindication to ARB administration or prior history of angioedema Persistent uncontrolled hypertension Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCZ696 at doses of 50mg, 100mg and 200mg b.i.d<br>randomized in a 1:1 ratio: LCZ696 to placebo | Drug: LCZ696<br>* LCZ696 at doses of 50mg, 100mg and 200mg b.i.d oral<br>* Other names: valsartan;|
| Placebo Comparator: Placebo to LCZ696<br>randomized in a 1:1 ratio: LCZ696 to placebo | Drug: Placebo<br>* placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in peak VO2 as measured by cardiopulmonary exercise test (CPET) | The primary analysis will assess the effect of LCZ696 on the change from baseline in peak VO2 (ml/kg/min) at week 50 compared to placebo, where baseline peak VO2 will come from the screening/baseline CPET. | Baseline to 50 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
non-obstructive, hypertrophic cardiomyopathy, genetic cardiomyopathy