A Study to Evaluate the Efficacy and Safety of Sotagliflo... | NCT06481891

NCT06481891

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Sotagliflozin	Experimental	Following an up to 3-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
Placebo	Placebo Comparator	Following an up to 3-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

Name	Type	Description	Arm Group Labels	Other Names
Sotagliflozin	Drug	Sotagliflozin will be administered as a tablet(s), orally once daily.	Sotagliflozin

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

Eligibility Criteria

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) or appropriate implantable cardioverter defibrillator (ICD) discharge 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.

ID	Term
D009202	Cardiomyopathies
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D001020	Aortic Stenosis, Subvalvular
D001024	Aortic Valve Stenosis
D000082862	Aortic Valve Disease
D006349	Heart Valve Diseases