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

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)

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.

Study Overview

• Status: Completed
• Conditions: Cardiomyopathy, Hypertrophic
• Intervention / Treatment: Drug: Placebo; Drug: LCZ696

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10789
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Kiel, Germany, 24105
    • Novartis Investigative Site
• Greece
  • Heraklion Crete, Greece, 711 10
    • Novartis Investigative Site
  • GR
    • Athens, GR, Greece, 151 23
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 05505
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28222
    • Novartis Investigative Site
  • Madrid, Spain, 280796
    • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • Novartis Investigative Site
• United States
  • California
    • Stanford, California, United States, 94305-5826
      • Novartis Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Novartis Investigative Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109 5271
      • Novartis Investigative Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2020
• Primary Completion (Actual): August 22, 2023
• Study Completion (Actual): August 22, 2023

Study Registration Dates

• First Submitted: November 13, 2019
• First Submitted That Met QC Criteria: November 13, 2019
• First Posted (Actual): November 15, 2019

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: hypertrophic cardiomyopathy; non-obstructive; genetic cardiomyopathy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Hypertrophy; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: CLCZ696I12201; 2019-003098-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No