Open-label Extension Study to Evaluate Long-term Safety of Sacubitril/Valsartan in Pediatric Patients With HF

A Multicenter Study to Evaluate Long-term Safety and Tolerability of Open Label Sacubitril/Valsartan in Pediatric Patients With Heart Failure Due to Systemic Left Ventricle Systolic Dysfunction Who Have Completed Study CLCZ696B2319

The purpose of this study was to evaluate long-term safety and tolerability and to provide post-trial access to sacubitril/valsartan to eligible participants who successfully completed CLCZ696B2319 (PANORAMA-HF) core study Part 2 as per protocol.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: sacubitril/valsartan

Detailed Description

This was a multicenter, open-label long-term extension study for participants who successfully completed PANORAMA-HF core study Part 2 of the trial or who discontinued study drug treatment early in Part 2 due to the implementation of Urgent safety measure (USM) of PANORAMA-HF core study. Provided that they fulfilled the protocol requirements, these patients were eligible to participate in the OLE. Depending on when and where the participant was enrolled, the duration of the study was of a minimum of 1 year, or until receipt of local marketing authorization and commercial availability, or reaching the maximum limit allowed by local regulations, or until Dec-2023, whichever occurred first.

• Study Type: Interventional
• Enrollment (Actual): 216
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Provincia De Salta
    • Ciudad de Salta, Provincia De Salta, Argentina, A4406BPF
      • Novartis Investigative Site
• Austria
  • Innsbruck, Austria, 6020
    • Novartis Investigative Site
• Bulgaria
  • Sofia, Bulgaria, 1309
    • Novartis Investigative Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1C9
      • Novartis Investigative Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Novartis Investigative Site
• Croatia
  • Zagreb, Croatia, 10000
    • Novartis Investigative Site
• Czechia
  • Praha 5, Czechia, 150 06
    • Novartis Investigative Site
• Finland
  • Helsinki, Finland, 00290
    • Novartis Investigative Site
• France
  • Paris 15, France, 75015
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Stuttgart, Germany, 70174
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, H 1096
    • Novartis Investigative Site
• India
  • New Delhi, India, 110029
    • Novartis Investigative Site
  • Delhi
    • New Delhi, Delhi, India, 110076
      • Novartis Investigative Site
  • Gujarat
    • Ahmedabad, Gujarat, India, 380 060
      • Novartis Investigative Site
  • Kerala
    • Kochi, Kerala, India, 682041
      • Novartis Investigative Site
• Israel
  • Beer Sheva, Israel, 84101
    • Novartis Investigative Site
• Italy
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • BG
    • Bergamo, BG, Italy, 24127
      • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • FI
    • Firenze, FI, Italy, 50132
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20162
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00165
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10126
      • Novartis Investigative Site
• Japan
  • Saitama, Japan, 330 8777
    • Novartis Investigative Site
  • Aichi
    • Obu, Aichi, Japan, 474 8710
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo city, Hokkaido, Japan, 060 8648
      • Novartis Investigative Site
  • Nagasaki
    • Omura, Nagasaki, Japan, 856-8562
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo ku, Tokyo, Japan, 113 8655
      • Novartis Investigative Site
    • Setagaya-ku, Tokyo, Japan, 157-8535
      • Novartis Investigative Site
    • Shinjuku ku, Tokyo, Japan, 162 8666
      • Novartis Investigative Site
  • Toyama
    • Toyama-city, Toyama, Japan, 930-0194
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 06351
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 03722
    • Novartis Investigative Site
  • Gyeongsangnam Do
    • Yangsan Si, Gyeongsangnam Do, Korea, Republic of, 50612
      • Novartis Investigative Site
• Lebanon
  • Ashrafieh, Lebanon, 166830
    • Novartis Investigative Site
  • Beirut, Lebanon, 10999
    • Novartis Investigative Site
• Poland
  • Warszawa, Poland, 04 730
    • Novartis Investigative Site
  • Wroclaw, Poland, 51-124
    • Novartis Investigative Site
• Portugal
  • Coimbra, Portugal, 3000 075
    • Novartis Investigative Site
  • Lisboa, Portugal, 1169 024
    • Novartis Investigative Site
  • Lisboa
    • Carnaxide, Lisboa, Portugal, 2799 523
      • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 125412
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 197341
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119260
    • Novartis Investigative Site
  • Singapore, Singapore, 229899
    • Novartis Investigative Site
• South Africa
  • Gauteng
    • Soweto, Gauteng, South Africa, 2013
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Andalucia
    • Cordoba, Andalucia, Spain, 14004
      • Novartis Investigative Site
  • Barcelona
    • Esplugues De Llobregat, Barcelona, Spain, 08950
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
• Switzerland
  • Lausanne, Switzerland, 1011
    • Novartis Investigative Site
• Taiwan
  • Tainan, Taiwan, 70403
    • Novartis Investigative Site
  • Taipei, Taiwan, 10041
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
  • Bangkok
    • Bangkoknoi, Bangkok, Thailand, 10700
      • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06490
    • Novartis Investigative Site
  • Izmir, Turkey, 35040
    • Novartis Investigative Site
  • Konak-Izmir, Turkey, 35210
    • Novartis Investigative Site
• United States
  • California
    • Loma Linda, California, United States, 92354
      • Novartis Investigative Site
    • Los Angeles, California, United States, 90095
      • Novartis Investigative Site
    • Palo Alto, California, United States, 94304
      • Novartis Investigative Site
  • Florida
    • Saint Petersburg, Florida, United States, 33701
      • Novartis Investigative Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Novartis Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Novartis Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Novartis Investigative Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5238
      • Novartis Investigative Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Novartis Investigative Site
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Novartis Investigative Site
  • New York
    • New York, New York, United States, 10032
      • Novartis Investigative Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Novartis Investigative Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Novartis Investigative Site
    • Pittsburgh, Pennsylvania, United States, 15224
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent
• On study drug at PANORAMA-HF Part 2 EOS visit. Does not have any significant safety issue

Exclusion Criteria:

• Subject only participated in PANORAMA-HF Part 1 or was a SF in PANORAMA-HF or permanently discontinued study drug in PANORMA-HF Part 2
• Use of investigational drugs within 5 half-lives of enrollment or within 30 days (longer duration); with the exception of PANORAMA-HF study drug (requires >/=36-hour washout before baseline visit)
• History of hypersensitivity or allergy to study treatment, its excipients or drugs of similar chemical class, ACEIs, ARBs, or NEP inhibitor and known/suspected contraindications to sacubitril/valsartan
• Renal vascular hypertension (including renal artery stenosis)
• Significant renal estimated glomerular filtration rate disorder (eGFR calculated using modified Schwartz formula <30% mean GFR for age); hepatic disorder (serum aspartate aminotransferase or alanine aminotransferase > 3 times upper limit of normal); gastrointestinal disorder or biliary disorder
• History of angioedema
• Parents or legal guardians of subject who do not give consent or allow the child to give assent, or inability of patient or parents/legal guardians to follow instructions or comply with follow-up procedures
• Any medical condition(s) that may put the patient at risk in the investigator's opinion or that the investigator deems unsuitable for the study
• Other protocol defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sacubitril/valsartan; single arm, open label sacubitril/valsartan	Drug: sacubitril/valsartan; Target dose 3.1 mg/kg bid Formulations: Tablets (50, 100, 200 mg) Granules [12.5 mg (4 granules), 31.25 mg (10 granules), in capsules] Liquid (1 mg/ml, 4 mg/ml, prepared from tablets); Other Names: LCZ696

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Number of participants with at least one Adverse Events (AEs)	to end of study, up to 4,5 years
Number of Participants With Serious Adverse Events	Number of participants with at least one Serious Adverse Events (SAEs)	to end of study, up to 4.5 years
Duration of Drug Exposure	Median duration of exposure to sacubitril/valsartan (including temporary interruptions)	Up to 4.5 years

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2019
• Primary Completion (Actual): December 29, 2023
• Study Completion (Actual): December 29, 2023

Study Registration Dates

• First Submitted: December 20, 2018
• First Submitted That Met QC Criteria: December 20, 2018
• First Posted (Actual): December 24, 2018

Study Record Updates

• Last Update Posted (Actual): May 16, 2025
• Last Update Submitted That Met QC Criteria: May 14, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: pediatric; heart failure; LCZ696; open-label study; sacubitril/valsartan; angiotensin receptor neprilysin inhibitor; PANORAMA-HF
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; 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: CLCZ696B2319E1

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