A Study to Evaluate the Efficacy and Safety of Sotagliflozin in Symptomatic Obstructive and Non-obstructive Hypertrophic Cardiomyopathy (SONATA-HCM)

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of SOtaglifloziN in symptomATic Obstructive And Non-obstructive Hypertrophic CardioMyopathy (SONATA-HCM)

The main purpose of the study is to determine the changes in symptoms and functional limitations in participants with symptomatic hypertrophic cardiomyopathy (HCM) treated with sotagliflozin as compared to placebo.

Study Overview

• Status: Recruiting
• Conditions: Non-obstructive Hypertrophic Cardiomyopathy; Obstructive Cardiomyopathy, Hypertrophic
• Intervention / Treatment: Drug: Sotagliflozin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tracy Newbold; Phone Number: 281-863-3016; Email: tnewbold@lexpharma.com

Study Locations

• United States
  • Indiana
    • Merrillville, Indiana, United States, 46410
      • Recruiting
      • Lexicon Investigational Site (4036)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• KCCQ CSS < 85.
• NYHA functional class II or III
• A diagnosis of HCM consistent with the current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guideline definition: unexplained left ventricular (LV) hypertrophy with nondilated ventricular chambers in the absence of other cardiac (eg, hypertension, aortic stenosis) or systemic disease with maximal LV wall thickness ≥ 15 millimeters (mm), or ≥ 13 mm with positive family history of HCM.
• For obstructive hypertrophic cardiomyopathy (oHCM), left ventricular outflow tract (LVOT) peak gradient ≥ 30 millimetre of mercury (mm Hg) during screening as assessed by echocardiography at rest or during a valsalva maneuver.
• For nonobstructive hypertrophic cardiomyopathy (nHCM), LVOT peak gradient < 30 mm Hg during screening as assessed by echocardiography at rest and < 30 mm Hg during a valsalva maneuver.
• Screening left ventricular ejection fraction (LVEF) ≥ 50%, except for those on a cardiac myosin inhibitor (screening LVEF ≥ 55%).
• For participants on a cardiac myosin inhibitor, the dose must be stable at least 3 months prior to screening. Participants on cardiac myosin inhibitor should not be scheduled for up-titration during the trial.
• Stable doses of background therapy (ie, β-blockers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, diuretics) for at least 1 month prior to screening.

Exclusion Criteria:

• Received therapy with a sodium glucose co-transporter 2 (SGLT2) inhibitor within the past 8 weeks prior to screening.
• Previous intolerance to an SGLT2 inhibitor.
• Any previous treatment with sotagliflozin.
• Current use of thiazolidinediones or digoxin.
• Current/planned participation in another interventional clinical trial or prior participation in any interventional trial with an investigational agent within 45 days of screening.
• Known infiltrative or storage disorder causing cardiac hypertrophy that mimics HCM such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy.
• History of unexplained syncope within 6 months prior to screening.
• History of sustained ventricular tachyarrhythmia (> 30 seconds) within 6 months prior to screening.
• Has paroxysmal, persistent, or permanent atrial fibrillation not on anticoagulation for at least 4 weeks prior to screening and/or not adequately rate controlled within 3 months of screening.
• Septal reduction therapy planned during the study period. For participants who had septal reduction therapy, the procedure should have been completed more than 3 months prior to screening.
• Cardiac surgery (eg, coronary artery bypass graft, valvular repair/replacement), percutaneous coronary intervention, or implantation of cardiac device (pacemaker or implantable cardioverter defibrillator) within 3 months prior to screening or planned during the study period.
• Presence of a cardiac resynchronization therapy device.
• Acute coronary syndrome within 2 months prior to screening.
• History of stroke or myocardial infarction within 6 months prior to screening.
• Hospitalization for heart failure or arrhythmia within 4 weeks prior to screening.
• Has known moderate or severe (as per investigator's judgment) aortic valve stenosis at screening.
• Current angina or clinically significant ischemia due to unstable epicardial coronary disease, as per investigator judgment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sotagliflozin; Following a 2-week screening period, sotagliflozin 400 milligrams (mg) tablets will be administered as two 200 mg tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 26 weeks.	Drug: Sotagliflozin; Sotagliflozin will be administered as a tablet(s), orally once daily.; Other Names: SAR439954/LX4211
Placebo Comparator: Placebo; Following a 2-week screening period, sotagliflozin-matching placebo 400 mg tablets will be administered as two 200 mg tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 26 weeks.	Drug: Placebo; Placebo will be administered as a tablet(s) (identical to the sotagliflozin tablet in appearance), orally once daily.; Other Names: SAR439954/LX4211

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline to Week 26 in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS)	KCCQ is a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores are generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. Higher scores reflect better health status.	Baseline to Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants at Week 26 with a New York Heart Association (NYHA) Functional Class Improvement ≥ 1 Category	NYHA functional class is a clinician-reported assessment of participants' health status on a 4-point scale, where Class I represents no limitations in normal activity; Class II indicates slight limitation of physical activity; Class III indicates marked limitation in physical activity; and Class IV indicates that participants have symptoms with any physical activity or at rest. Percentage of participants with NYHA functional class improvement ≥1 will be reported.	Week 26
Change from Baseline to Week 26 in KCCQ Total Symptom Score (TSS).	KCCQ is a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their HF symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores are generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. Higher scores reflect better health status.	Baseline to Week 26

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): June 28, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: June 25, 2024
• First Submitted That Met QC Criteria: June 25, 2024
• First Posted (Estimated): July 1, 2024

Study Record Updates

• Last Update Posted (Estimated): July 1, 2024
• Last Update Submitted That Met QC Criteria: June 25, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• 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; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
• Other Study ID Numbers: LX4211.1-314-HCM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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