Clinical trial NCT06481891: A Study to Evaluate the Efficacy and Safety of Sotagliflozin in Symptomatic Obstructive and Non-obstructive Hypertrophic Cardiomyopathy
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Obstructive Cardiomyopathy, Hypertrophic
Non-obstructive Hypertrophic Cardiomyopathy
Lead sponsor: Lexicon Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-07-01
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: Change from Baseline to Week 26 in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS)
timeFrame: Baseline to Week 26
Secondary outcomes:
measure: Percentage of Participants at Week 26 with a New York Heart Association (NYHA) Functional Class Improvement ≥ 1 Category
timeFrame: Week 26
measure: Change from Baseline to Week 26 in KCCQ Total Symptom Score (TSS).
timeFrame: Baseline to Week 26
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Lexicon Investigational Site (4037)
state: Arizona
city: Los Angeles
country: United States
facility: Lexicon Investigational Site (4012)
state: California
city: Pomona
country: United States
facility: Lexicon Investigational Site (4035)
state: California
city: Orlando
country: United States
facility: Lexicon Investigational Site (4034)
state: Florida
city: Atlanta
country: United States
facility: Lexicon Investigational Site (4018)
state: Georgia
city: Evanston
country: United States
facility: Lexicon Investigational Site (4033)
state: Illinois
city: Merrillville
country: United States
facility: Lexicon Investigational Site (4036)
state: Indiana
city: Baltimore
country: United States
facility: Lexicon Investigational Site (4021)
state: Maryland
city: Boston
country: United States
facility: Lexicon Investigational Site (4016)
state: Massachusetts
city: Ann Arbor
country: United States
facility: Lexicon Investigational Site (4028)
state: Michigan
city: Grand Rapids
country: United States
facility: Lexicon Investigational Site (4038)
state: Michigan
city: Rochester
country: United States
facility: Lexicon Investigational Site (4027)
state: Minnesota
city: Saint Louis
country: United States
facility: Lexicon Investigational Site (4013)
state: Missouri
city: Morristown
country: United States
facility: Lexicon Investigational Site (4029)
state: New Jersey
city: Manhasset
country: United States
facility: Lexicon Investigational Site (4039)
state: New York
city: Morrisville
country: United States
facility: Lexicon Investigational Site (4026)
state: North Carolina
city: Cincinnati
country: United States
facility: Lexicon Investigational Site (4031)
state: Ohio
city: Tulsa
country: United States
facility: Lexicon Investigational Site (4024)
state: Oklahoma
city: Philadelphia
country: United States
facility: Lexicon Investigational Site (4011)
state: Pennsylvania
city: Germantown
country: United States
facility: Lexicon Investigational Site (4019)
state: Tennessee
city: Houston
country: United States
facility: Lexicon Investigational Stie (4014)
state: Texas
city: Charlottesville
country: United States
facility: Lexicon Investigational Site (4032)
state: Virginia
city: Marshfield
country: United States
facility: Lexicon Investigational Site (4022)
state: Wisconsin
city: Milwaukee
country: United States
facility: Lexicon Investigational Site (4040)
state: Wisconsin
city: Santa Rosa
country: Argentina
facility: Lexicon Investigational Site (5016)
state: La Pampa
city: Rosario
country: Argentina
facility: Lexicon Investigational Site (5012)
state: Santa Fe
city: Corrientes
country: Argentina
facility: Lexicon Investigational Site (5015)
city: Córdoba
country: Argentina
facility: Lexicon Investigational Site (5010)
city: Córdoba
country: Argentina
facility: Lexicon Investigational Site (5013)
city: Santa Fe
country: Argentina
facility: Lexicon Investigational Site (5014)
city: Genk
country: Belgium
facility: Lexicon Investigational Site (1012)
city: Campinas
country: Brazil
facility: Lexicon Investigational Site (5110)
state: Sao Paulo
city: Tbilisi
country: Georgia
facility: Lexicon Investigational Site (1611)
city: Tbilisi
country: Georgia
facility: Lexicon Investigational Site (1610)
city: Tbilisi
country: Georgia
facility: Lexicon Investigational Site (1612)
city: Tbilisi
country: Georgia
facility: Lexicon Investigational Site (1613)
city: Be'er Ya'aqov
country: Israel
facility: Lexicon Investigational Site (7017)
city: Haifa
country: Israel
facility: Lexicon Investigational Site (7014)
city: Jerusalem
country: Israel
facility: Lexicon Investigational Site (7011)
city: Petah tikva
country: Israel
facility: Lexicon Investigational Site (7016)
city: Napoli
country: Italy
facility: Lexicon Investigational Site (1813)
city: Belgrade
country: Serbia
facility: Lexicon Investigational Site (2312)
city: Belgrade
country: Serbia
facility: Lexicon Investigational Site (2314)
city: Belgrade
country: Serbia
facility: Lexicon Investigational Site (2311)
city: Belgrade
country: Serbia
facility: Lexicon Investigational Site (2313)
city: Niš
country: Serbia
facility: Lexicon Investigational Site (2310)
city: Glasgow
country: United Kingdom
facility: Lexicon Investigational Site (2712)
city: Leicester
country: United Kingdom
facility: Lexicon Investigational Site (2713)
city: Liverpool
country: United Kingdom
facility: Lexicon Investigational Site (2710)
city: London
country: United Kingdom
facility: Lexicon Investigational Site (2711)
Study officials:
References: