TXA127 treatment for non-ambulant patients with DMD cardiomyopathy

A Phase 2, Single-Arm, Open-Label, Multi-Center Study to Evaluate the Safety and Efficacy of TXA127/Angiotensin [1-7] in Non-Ambulant Patients With Duchenne Muscular Dystrophy (DMD) Cardiomyopathy Who Are Receiving Systemic Glucocorticoids

This study is testing if a new treatment called TXA127 can help improve heart function and overall health in boys and men with Duchenne muscular dystrophy who have heart problems.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 16 Years and up
• Sex: Male
• Sponsor: Constant Therapeutics LLC (Industry-sponsored)
• Locations: 2 sites (Jerusalem and 1 other locations)
• Trial ID: NCT06013839 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm multi-center study evaluates the safety and efficacy of TXA127 in male patients aged 16 and older with Duchenne muscular dystrophy (DMD) associated cardiomyopathy. Participants will receive daily subcutaneous injections of TXA127 for six months, followed by an optional 12-month extension phase to gather long-term safety data. The study will assess treatment safety through various clinical evaluations and monitor efficacy through measures such as ejection fraction and upper extremity strength. The trial aims to provide insights into the potential benefits of TXA127 for this patient population.

Who should consider this trial

Good fit: Ideal candidates are male patients aged 16 years or older with a documented diagnosis of DMD and cardiomyopathy.

Not a fit: Patients who are ambulant or do not have documented cardiomyopathy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve heart function and overall health in patients with DMD cardiomyopathy.

How similar studies have performed: While this approach is novel for DMD cardiomyopathy, similar studies in related conditions have shown promising results.

Eligibility criteria

Inclusion Criteria:

1. Male subjects 16 years of age or older who provide informed consent and can follow up with protocol procedures. Parental or guardian consent is required for subjects at least 16 years of age but younger than 18 years of age.
2. Documented diagnosis of Duchenne muscular dystrophy by genetic mutation analysis.
3. Documented cardiomyopathy, as assessed by echocardiogram with:

   1. For a patient ≤ 20 years of age, EF \> 35% and \< 55% and fractional shortening of ≤ 28% at the time of screening.
   2. For a patient \> 20 years of age, EF \> 20% and fractional shortening ≤ 28% at the time of screening.
4. Reproducible (+/- 10%) difference between screening and baseline of percent predicted FVC , using the best out of 3 efforts at each visit:

   1. For a patient ≤ 20 years of age, FVC between 45% and 85%, inclusive. Patient should not utilize non-invasive ventilation such as CPAP or BiPAP.
   2. For a patient \>20 years of age, all of the following should exist: FVC \> 20%, EF \> 20% in baseline ECHO and ability to be off non-invasive ventilation, such as CPAP and BiPAP, for at least 4 consecutive hours a day (24 hours period).
5. Subjects must be taking systemic glucocorticoids for at least six months prior to screening.
6. Subjects taking mineralocorticoid receptor antagonists, must be taking the drug for at least three months prior to screening
7. Non-ambulant and cared for by a trained caregiver

Exclusion Criteria:

1. Therapy with intravenous inotropic or vasoactive medications at the time of screening
2. Planned or likelihood of major surgery in the 6 months after planned enrollment.
3. Patient is using a left ventricular assist device (LVAD) or actively in the process of acquiring a LVAD.
4. Estimated glomerular filtration rate (GFR) \<50 mL/min, as calculated by the CKD-EPI Creatinine equation 2021 (https://www.kidney.org/professionals/kdoqi/gfr_calculator)
5. Patient is suffering from unstable systemic allergic reaction(s), connective tissue disease or autoimmune disorder(s), requiring active intervention
6. History of cardiac tumor or current cardiac tumor
7. Known moderate-to-severe aortic stenosis/insufficiency or severe mitral stenosis/regurgitation
8. Current alcohol or drug abuse
9. Known history of chronic viral hepatitis unless considered cured based on hepatitis C RNA negative results
10. Hepatic dysfunction upon screening evidenced by bilirubin levels or gamma-GT levels above normal, deemed as clinically significant by the PI/Sub-I, and/or abnormal hematology (hematocrit \<25%, WBC \<3000/μl, platelets \<100,000/μl), without a reversible, identifiable cause. Total bilirubin elevations \> 2 times the upper reference range, consistent with Gilbert's Syndrome, may be enrolled if there is no other evidence of liver dysfunction
11. Uncontrolled diabetes (HbA1c \>9.0 percent)
12. Inability to comply with protocol-related procedures, including required study visits
13. Any condition or other reason that, in the opinion of the investigator or Medical Monitor, would render the subject unsuitable for the study
14. Currently receiving or received within 90 days of enrollment (Day 1) an investigational treatment on another clinical study or expanded access protocol. This will include patients currently being treated or who have not completed follow-up to treatment with an investigational cell-based therapy within 6 months prior to enrollment and patients actively receiving an investigational therapy for cardiovascular repair/regeneration.

Where this trial is running

Jerusalem and 1 other locations

• Hadassah Medical Center — Jerusalem, Israel (Recruiting)
• Sheba Medical Center — Ramat Gan, Israel (Recruiting)

Study contacts

• Study coordinator: Richard L Franklin, MD, PhD

Conditions DMD-Associated Dilated Cardiomyopathy