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

Cardiomyopathy, Hypertrophic Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04164732
• Other study ID #: CLCZ696I12201
• Secondary ID: 2019-003098-24
• Status: Completed
• Phase: Phase 2
• Start date: January 8, 2020
• Est. completion date: August 22, 2023

Study information

• Verified date: September 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: August 22, 2023
• Est. primary completion date: August 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Hypertrophy

Intervention

Drug:
• LCZ696
LCZ696 at doses of 50mg, 100mg and 200mg b.i.d oral
• Placebo
placebo

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Kiel
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Heraklion Crete
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Spain	Novartis Investigative Site	El Palmar	Murcia
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
United Kingdom	Novartis Investigative Site	London
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany,  Greece,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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