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

NCT06481891 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: LX4211.1-314-HCM
• Study Type: interventional
• Target: 500
• Locations: 18 countries
• Sites: 102

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.

Conditions

Obstructive Cardiomyopathy, Hypertrophic; Non-obstructive Hypertrophic Cardiomyopathy

Outcome Measures

Primary Outcomes (1)

• 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 (2)

• Percentage of Participants at Week 26 with a New York Heart Association (NYHA) Functional Class Improvement ≥ 1 Category

  Week 26

• Change from Baseline to Week 26 in KCCQ Total Symptom Score (TSS).

  Baseline to Week 26

Study Arms (2)

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

Interventions

Sotagliflozin DRUG

Sotagliflozin will be administered as a tablet(s), orally once daily.

Also known as: SAR439954/LX4211

Sotagliflozin

Placebo DRUG

Placebo will be administered as a tablet(s) (identical to the sotagliflozin tablet in appearance), orally once daily.

Also known as: SAR439954/LX4211

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lexicon Pharmaceuticals: lead

Study Sites (107)

Lexicon Investigational Site (4041)

Phoenix, Arizona, 85054, United States

RECRUITING

Lexicon Investigational Site (4037)

Scottsdale, Arizona, 85260, United States

RECRUITING

Lexicon Investigational Site (4012)

Los Angeles, California, 90048, United States

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Lexicon Investigational Site (4035)

Pomona, California, 91767, United States

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Lexicon Investigational Site (4044)

San Francisco, California, 94143, United States

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Lexicon Investigational Site (4046)

Jacksonville, Florida, 32224, United States

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Lexicon Investigational Site (4034)

Orlando, Florida, 32804, United States

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Lexicon Investigational Site (4018)

Atlanta, Georgia, 30322, United States

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Lexicon Investigational Site (4033)

Evanston, Illinois, 60208, United States

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Lexicon Investigational Site (4036)

Merrillville, Indiana, 46410, United States

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Lexicon Investigational Site (4021)

Baltimore, Maryland, 21218, United States

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Lexicon Investigational Site (4016)

Boston, Massachusetts, 02115, United States

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Lexicon Investigational Site (4042)

Boston, Massachusetts, 02118, United States

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Lexicon Investigational Site (4028)

Ann Arbor, Michigan, 48109, United States

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Lexicon Investigational Site (4038)

Grand Rapids, Michigan, 49525, United States

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Lexicon Investigational Site (4027)

Rochester, Minnesota, 55905, United States

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Lexicon Investigational Site (4013)

St Louis, Missouri, 63110, United States

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Lexicon Investigational Site (4029)

Morristown, New Jersey, 07960, United States

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Lexicon Investigational Site (4039)

Manhasset, New York, 11030, United States

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Lexicon Investigational Site (4043)

New York, New York, 10016, United States

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Lexicon Investigational Site (4026)

Morrisville, North Carolina, 27560, United States

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Lexicon Investigational Site (4031)

Cincinnati, Ohio, 45219, United States

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Lexicon Investigational Site (4017)

Cleveland, Ohio, 44195, United States

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Lexicon Investigational Site (4024)

Tulsa, Oklahoma, 74104, United States

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Lexicon Investigational Site (4015)

Portland, Oregon, 97239, United States

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Lexicon Investigational Site (4011)

Philadelphia, Pennsylvania, 19104, United States

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Lexicon Investigational Site (4019)

Germantown, Tennessee, 38138, United States

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Lexicon Investigational Stie (4014)

Houston, Texas, 77030, United States

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Lexicon Investigational Site (4032)

Charlottesville, Virginia, 22908, United States

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Lexicon Investigational Site (4010)

Seattle, Washington, 98195, United States

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Lexicon Investigational Site (4022)

Marshfield, Wisconsin, 54449, United States

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Lexicon Investigational Site (4040)

Milwaukee, Wisconsin, 53215, United States

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Lexicon Investigational Site (5016)

Santa Rosa, La Pampa Province, L6304BWE, Argentina

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Lexicon Investigational Site (5012)

Rosario, Santa Fe Province, 2000, Argentina

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Lexicon Investigational Site (5015)

Corrientes, W3400CDS, Argentina

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Lexicon Investigational Site (5010)

Córdoba, 5002, Argentina

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Lexicon Investigational Site (5013)

Córdoba, X5000AAX, Argentina

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Lexicon Investigational Site (5011)

Salta, 4400, Argentina

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Lexicon Investigational Site (5014)

Santa Fe, 3000, Argentina

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Lexicon Investigational Site (1012)

Genk, 3600, Belgium

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Lexicon Investigational Site (5114)

Salvador, Estado de Bahia, 40170-130, Brazil

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Lexicon Investigational Site (5110)

Campinas, São Paulo, 13060-080, Brazil

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Lexicon Investigational Site (5112)

Recife, 52051-380, Brazil

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Lexicon Investigational Site (5115)

São Paulo, 04039-000, Brazil

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Lexicon Investigational Site (1112)

Rousse, 7013, Bulgaria

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Lexicon Investigational Site (1111)

Sofia, 1407, Bulgaria

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Lexicon Investigational Site (1215)

Krapinske Toplice, 49217, Croatia

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Lexicon Investigational Site (1212)

Opatija, 51410, Croatia

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Lexicon Investigational Site (1210)

Rijeka, 51000, Croatia

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Lexicon Investigational Site (1213)

Zagreb, 10000, Croatia

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Lexicon Investigational Site (1311)

Brno, 602 00, Czechia

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Lexicon Investigational Site (1310)

Prague, 128 08, Czechia

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Lexicon Investigational Site (1312)

Ústí nad Labem, 400 11, Czechia

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Lexicon Investigational Site (1514)

Chambray-lès-Tours, 37170, France

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Lexicon Investigational Site (1511)

Marseille, 13005, France

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Lexicon Investigational Site (1513)

Paris, 75651, France

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Lexicon Investigational Site (1510)

Poitiers, 86021, France

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Lexicon Investigational Site (1512)

Rennes, 35033, France

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Lexicon Investigational Site (1515)

Toulouse, 31059, France

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Lexicon Investigational Site (1611)

Tbilisi, 0112, Georgia

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Lexicon Investigational Site (1610)

Tbilisi, 0131, Georgia

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Lexicon Investigational Site (1612)

Tbilisi, 0144, Georgia

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Lexicon Investigational Site (1613)

Tbilisi, 0186, Georgia

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Lexicon Investigational Site (2813)

Berlin, 13353, Germany

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Lexicon Investigational Site (2812)

Hamburg, 22041, Germany

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Lexicon Investigational Site (2811)

Leipzig, 04289, Germany

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Lexicon Investigational Site (2810)

München, 80336, Germany

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Lexicon Investigational Site (1710)

Budapest, 1122, Hungary

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Lexicon Investigational Site (1711)

Pécs, 7624, Hungary

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Lexicon Investigational Site (1712)

Szeged, 6725, Hungary

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Lexicon Investigational Site (1713)

Zalaegerszeg, 8900, Hungary

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Lexicon Investigational Site (7017)

Be’er Ya‘aqov, 7033001, Israel

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Lexicon Investigational Site (7013)

Haifa, 3109601, Israel

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Lexicon Investigational Site (7014)

Haifa, 3339419, Israel

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Lexicon Investigational Site (7015)

Holon, 5822012, Israel

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Lexicon Investigational Site (7011)

Jerusalem, 9112001, Israel

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Lexicon Investigational Site (7016)

Petah Tikva, 4941492, Israel

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Lexicon Investigational Site (7012)

Ramat Gan, 5265601, Israel

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Lexicon Investigational Site (7019)

Tel Aviv, 6423906, Israel

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Lexicon Investigational Site (1814)

Arezzo, 52100, Italy

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Lexicon Investigational Site (1811)

Brescia, 25123, Italy

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Lexicon Investigational Site (1813)

Naples, 80131, Italy

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Lexicon Investigational Site (2114)

Lodz, 91-347, Poland

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Lexicon Investigational Site (2113)

Lodz, 92-213, Poland

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Lexicon Investigational Site (2115)

Oświęcim, 32-600, Poland

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Lexicon Investigational Site (2110)

Wroclaw, 50-981, Poland

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Lexicon Investigational Site (2210)

Braga, 4710-243, Portugal

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Lexicon Investigational Site (2213)

Faro, 8000-386, Portugal

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Lexicon Investigational Site (2211)

Lisbon, 1350-352, Portugal

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Lexicon Investigational Site (2215)

Lisbon, 1500-650, Portugal

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Lexicon Investigational Site (2218)

Lisbon, 1649-035, Portugal

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Lexicon Investigational Site (2216)

Lisbon, 1998-018, Portugal

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Lexicon Investigational Site (2217)

Porto, 4200-319, Portugal

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Lexicon Investigational Site (2910)

Baloteşti, 077015, Romania

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Lexicon Investigational Site (2913)

Suceava, 720049, Romania

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Lexicon Investigational Site (2911)

Târgu Mureş, 540124, Romania

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Lexicon Investigational Site (2912)

Târgu Mureş, 540143, Romania

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Lexicon Investigational Site (2312)

Belgrade, 11000, Serbia

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Lexicon Investigational Site (2314)

Belgrade, 11000, Serbia

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Lexicon Investigational Site (2311)

Belgrade, 11040, Serbia

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Lexicon Investigational Site (2313)

Belgrade, 11040, Serbia

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Lexicon Investigational Site (2310)

Niš, 18108, Serbia

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Lexicon Investigational Site (2510)

Stockholm, 17164, Sweden

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Lexicon Investigational Site (2712)

Glasgow, G51 4TF, United Kingdom

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Lexicon Investigational Site (2713)

Leicester, LE3 9QP, United Kingdom

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Lexicon Investigational Site (2710)

Liverpool, L14 3PE, United Kingdom

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Lexicon Investigational Site (2711)

London, EC1M 6BQ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Interventions

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Central Study Contacts

Tracy Newbold

CONTACT

281-863-3016; tnewbold@lexpharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2024
• First Posted: July 1, 2024
• Study Start: September 24, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

RO (4); PT (7); CZ (3); BE (1); CR (4); US (32); BR (4); IT (3); GB (4); AR (7); FR (6); SE (1); GE (4); DE (4); HU (4); BU (2); IL (8); PL (4)