A study to understand if sotagliflozin improves symptoms and is safe in people with hypertrophic cardiomyopathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Lexicon Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

27 Jun 2025 → ongoing

Decision date (initial)

2025-01-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Lexicon Pharmaceuticals Inc.

External identifiers

EU CT number

2024-513869-39-00

ClinicalTrials.gov

NCT06481891

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To determine the changes in symptoms and functional limitations in patients with symptomatic hypertrophic cardiomyopathy (HCM) treated with sotagliflozin as compared to placebo.

Secondary objectives 1

1. To determine the safety and tolerability of sotagliflozin as compared with placebo in patients with symptomatic HCM over the 26-week treatment period.

Conditions and MedDRA coding

Obstructive Cardiomyopathy, Hypertrophic

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. KCCQ CSS < 85.
2. NYHA functional class II or III
3. 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.
4. 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.
5. 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.
6. Screening left ventricular ejection fraction (LVEF) ≥ 50%, except for those on a cardiac myosin inhibitor (screening LVEF ≥ 55%).
7. 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.
8. 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 17

1. Received therapy with a sodium glucose co-transporter 2 (SGLT2) inhibitor within the past 8 weeks prior to screening.
2. Previous intolerance to an SGLT2 inhibitor.
3. Any previous treatment with sotagliflozin.
4. Current use of thiazolidinediones or digoxin.
5. Current/planned participation in another interventional clinical trial or prior participation in any interventional trial with an investigational agent within 45 days of screening.
6. Known infiltrative or storage disorder causing cardiac hypertrophy that mimics HCM such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy.
7. History of unexplained syncope within 6 months prior to screening.
8. History of sustained ventricular tachyarrhythmia (> 30 seconds) or appropriate ICD (implantable cardioverter defibrillator) discharge within the 6 months prior to Screening.
9. 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.
10. 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.
11. 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.
12. Presence of a cardiac resynchronization therapy device.
13. Acute coronary syndrome within 2 months prior to screening.
14. History of stroke or myocardial infarction within 6 months prior to screening.
15. Hospitalization for heart failure or arrhythmia within 4 weeks prior to screening.
16. Has known moderate or severe (as per investigator's judgment) aortic valve stenosis at screening.
17. Current angina or clinically significant ischemia due to unstable epicardial coronary disease, as per investigator judgment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline to Week 26 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS).

Secondary endpoints 5

1. Proportion of patients at Week 26 with a New York Heart Association (NYHA) functional class improvement ≥ 1 category
2. Change from Baseline to Week 26 in KCCQ Total Symptom Score (TSS)
3. Treatment-emergent adverse events (TEAEs) reported during the double-blind treatment period and through Week 30.
4. Clinical laboratory results (including serum creatinine and estimated glomerular filtration rate [eGFR]) and vital signs through Week 26.
5. Change from Baseline at Week 4 and Week 26 in left ventricular outflow tract (LVOT) gradient (at rest and with Valsalva maneuver) as measured by echocardiogram.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Lexicon Pharmaceuticals Inc.

Sponsor organisation

Lexicon Pharmaceuticals Inc.

Address

2445 Technology Forest Boulevard Suite 1100

City

The Woodlands

Postcode

77381-5261

Country

United States

Scientific contact point

Organisation

Lexicon Pharmaceuticals Inc.

Contact name

Lexicon Information

Public contact point

Organisation

Lexicon Pharmaceuticals Inc.

Contact name

Lexicon Information

Third parties 6

Locations

13 EU/EEA countries · 62 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 158 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications