Cardiomyopathy, HypertrophicPhase 2NCT04164732
Study of Efficacy of Oral Sacubitril/Valsartan in Adult Patients With Non-obstructive Hypertrophic Cardiomyopathy
A Phase 2 study testing LCZ696 in people with Cardiomyopathy, Hypertrophic, run by Novartis Pharmaceuticals at 18 sites in 6 countries.
Trial summary
The purpose of this study was to determine if LCZ696 can improve functional capacity (via improved peak VO2) in non-obstructive hypertrophic cardiomyopathy (HCM) patient population over the course of 50 weeks of treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiomyopathy, Hypertrophic
- What is being tested?
- LCZ696
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 18 sitesin 6 countries
- Study dates
- 8 Jan 2020to 22 Aug 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
18 sites in 6 countries.
18 sites in 6 countries
United States5 sites
Novartis Investigative Site
Ann Arbor, Michigan, 48109 5271
Novartis Investigative Site
Boston, Massachusetts, 02114
Novartis Investigative Site
Morristown, New Jersey, 07960
Novartis Investigative Site
Portland, Oregon, 97239
Novartis Investigative Site
Stanford, California, 94305-5826
Germany4 sites
Novartis Investigative Site
Berlin, 10789
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Kiel, 24105
Spain4 sites
Novartis Investigative Site
El Palmar, Murcia, 30120
Novartis Investigative Site
Madrid, 280796
Novartis Investigative Site
Madrid, 28222
Novartis Investigative Site
Valencia, Valencia, 46010
Greece2 sites
Novartis Investigative Site
Athens, GR, 151 23
Novartis Investigative Site
Heraklion Crete, 711 10
South Korea2 sites
Novartis Investigative Site
Seoul, 03722
Novartis Investigative Site
Seoul, 05505
About this study
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)
The purpose of this study was to determine if LCZ696 can improve functional capacity (via improved peak VO2) in non-obstructive hypertrophic cardiomyopathy (HCM) patient population over the course of 50 weeks of treatment.
Read the detailed description
This was a multi-center, placebo-controlled, patient and investigator-blinded study in non-obstructive HCM patients.
The study comprised a ≤ 35-day screening/baseline period, a 4-week single-blind treatment run-in period, followed by a 46-week double-blind placebo-controlled treatment period (total treatment period of 50 weeks), and a follow-up period approximately 30 days after the last dose.
The treatment run-in period was planned to ensure that as large a proportion as possible of patients:
- had stable symptoms and could comply with study visits, and
- could tolerate at least low dose LCZ696. During the run-in period, all patients received oral (p.o.) placebo b.i.d. for 2 weeks followed by 50 mg p.o. of active LCZ696 b.i.d. for 2 weeks. Patients who were unable to tolerate either placebo or the 50 mg p.o. b.i.d. dose level, were considered treatment run-in failures and were neither randomized into the double-blind, placebo-controlled study, nor included in the efficacy analysis.
In the double-blind treatment period, participants were randomized 1:1 to placebo or LCZ696. In the LCZ696 arm, participants started at a LCZ696 100 mg p.o. b.i.d dose. After approximately 14 days, patients who tolerated the 100 mg p.o. b.i.d. dose were up-titrated to 200 mg p.o. b.i.d. dose, whereas those who did not meet the safety criteria were titrated back down to the 50 mg b.i.d. dose.
- Conditions
- Cardiomyopathy, Hypertrophic
- Being tested
- LCZ696, Placebo
- Keywords
- non-obstructive, hypertrophic cardiomyopathy, genetic cardiomyopathy
- Medical subject headings
- Cardiomyopathy, Hypertrophic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LCZ696Drug
Also called sacubitril, valsartan
LCZ696 orally twice daily
PlaceboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| LCZ696 BID | Experimental | Patients were treated with LCZ696. The target dose level was 200 mg p.o. b.i.d. Receives: Drug: LCZ696 |
| Placebo BID | Placebo comparator | Placebo to LCZ696 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Peak VO2 as Measured by Cardiopulmonary Exercise Test (CPET)
The primary analysis assessed the effect of LCZ696 on the change from baseline in peak Volume of Oxygen (VO2) (ml/kg/min) at week 50 compared to placebo, where baseline peak VO2 came from the screening/baseline CPET.
An increase in peak VO2 (mL/kg/min)/positive change is considered beneficial for the patient.
Measured: Baseline to 50 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2019
- Study start8 Jan 2020
- Primary completion22 Aug 2023
- Study completion22 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cardiomyopathy, HypertrophicStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04164732
- Sponsor's protocol ID
- CLCZ696I12201
- Other IDs
- 2019-003098-24, 2019
- Status last verified
- May 2025
- First submitted
- 13 Nov 2019
- Last updated
- 16 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04164732
- Acronym / sponsor ID
- CLCZ696I12201
- Conditions
- Cardiomyopathy, Hypertrophic
- Keywords
- non-obstructive, hypertrophic cardiomyopathy, genetic cardiomyopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 8 Jan 2020 (actual)
- Primary completion
- 22 Aug 2023 (actual)
- Study completion
- 22 Aug 2023 (actual)
- First posted
- 15 Nov 2019 (actual)
- Results
- Posted 29 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to determine if LCZ696 can improve functional capacity (via improved peak VO2) in non-obstructive hypertrophic cardiomyopathy (HCM) patient population over the course of 50 weeks of treatment.
Detailed description
This was a multi-center, placebo-controlled, patient and investigator-blinded study in non-obstructive HCM patients.
The study comprised a ≤ 35-day screening/baseline period, a 4-week single-blind treatment run-in period, followed by a 46-week double-blind placebo-controlled treatment period (total treatment period of 50 weeks), and a follow-up period approximately 30 days after the last dose.
The treatment run-in period was planned to ensure that as large a proportion as possible of patients:
- had stable symptoms and could comply with study visits, and
- could tolerate at least low dose LCZ696. During the run-in period, all patients received oral (p.o.) placebo b.i.d. for 2 weeks followed by 50 mg p.o. of active LCZ696 b.i.d. for 2 weeks. Patients who were unable to tolerate either placebo or the 50 mg p.o. b.i.d. dose level, were considered treatment run-in failures and were neither randomized into the double-blind, placebo-controlled study, nor included in the efficacy analysis.
In the double-blind treatment period, participants were randomized 1:1 to placebo or LCZ696. In the LCZ696 arm, participants started at a LCZ696 100 mg p.o. b.i.d dose. After approximately 14 days, patients who tolerated the 100 mg p.o. b.i.d. dose were up-titrated to 200 mg p.o. b.i.d. dose, whereas those who did not meet the safety criteria were titrated back down to the 50 mg b.i.d. dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LCZ696 BID | Experimental | Drug: LCZ696Patients were treated with LCZ696. The target dose level was 200 mg p.o. b.i.d. |
| Placebo BID | Placebo comparator | Drug: PlaceboPlacebo to LCZ696 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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:
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LCZ696Also: sacubitril, valsartanLCZ696 orally twice daily | Drug | LCZ696 BID |
| Placeboplacebo | Drug | Placebo BID |
Primary outcome
Change From Baseline in Peak VO2 as Measured by Cardiopulmonary Exercise Test (CPET)
Time frame: Baseline to 50 weeks
The primary analysis assessed the effect of LCZ696 on the change from baseline in peak Volume of Oxygen (VO2) (ml/kg/min) at week 50 compared to placebo, where baseline peak VO2 came from the screening/baseline CPET. An increase in peak VO2 (mL/kg/min)/positive change is considered beneficial for the patient.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
18 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LCZ696 in people with Cardiomyopathy, Hypertrophic, run by Novartis Pharmaceuticals at 18 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Germany, Spain, Greece, South Korea and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Peak VO2 as Measured by Cardiopulmonary Exercise Test (CPET) (time frame: Baseline to 50 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2025.