TXA127 in Non-Ambulant Patients With DMD Cardiomyopathy

Study Overview
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Brief Summary
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This open-label, single-arm multi-center study studying the safety and efficacy of TXA127 on non-ambulant patients with DMD Cardiomyopathy will comprise of two phases: 6-month open-label treatment phase: Male DMD patients with documented cardiomyopathy, will receive a daily subcutaneous injection of TXA127 0.5 mg/kg. Treatment will be provided for 6 months. Treatment safety will be assessed by collection and review of AEs, vital signs, ECGs, physical examinations, PFTs, and laboratory parameters on Day 1, Month 1, and Month 6. Ejection Fraction, upper extremity strength and biomarker levels will be assessed at these study visits as well. In addition, an abbreviated safety visit will be conducted at Month 3. 12-month optional extension phase: Patients will continue the same study drug regime for an additional 12 months. The primary objective of this phase is to obtain long-term safety data. Efficacy data will also be collected. Safety, efficacy, and exploratory biomarkers will be assessed at Month 12 and Month 18, using the same methods as in the treatment phase. In addition, abbreviated safety visits will be conducted at Month 9 and Month 15.

Official Title
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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

Conditions
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DMD-Associated Dilated Cardiomyopathy

Intervention / Treatment
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* Drug: talfirastide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Documented diagnosis of Duchenne muscular dystrophy by genetic mutation analysis. Documented cardiomyopathy, as assessed by echocardiogram with EF >35% and <55% and fractional shortening of ≤ 28% at the time of screening. Subjects must be taking systemic glucocorticoids for at least six months prior to screening. Subjects taking mineralocorticoid receptor antagonists, must be taking the drug for at least three months prior to screening Non-ambulant and cared for by a trained caregiver Exclusion Criteria: Therapy with intravenous inotropic or vasoactive medications at the time of screening Planned or likelihood of major surgery in the 6 months after planned enrollment. Patient is using a left ventricular assist device (LVAD) or actively in the process of acquiring a LVAD. 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) Reproducible (+/- 10%) difference between screening and baseline, percent predicted FVC between 45 and 85, inclusive, using best of 3 efforts at each visit Patients with non-invasive ventilation, such as CPAP and BiPAP Patient is suffering from unstable systemic allergic reaction(s), connective tissue disease or autoimmune disorder(s), requiring active intervention History of cardiac tumor or current cardiac tumor Known moderate-to-severe aortic stenosis/insufficiency or severe mitral stenosis/regurgitation Current alcohol or drug abuse Known history of chronic viral hepatitis unless considered cured based on hepatitis C RNA negative results 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 Uncontrolled diabetes (HbA1c >9.0 percent) Inability to comply with protocol-related procedures, including required study visits Any condition or other reason that, in the opinion of the investigator or Medical Monitor, would render the subject unsuitable for the study 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.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TXA127 SC 0.5mg/kg/day<br>TXA127 (talfirastide) 0.5mg/kg/day given via subcutaneous injection for 6 months | Drug: talfirastide<br>* TXA127 (talfirastide) is a pharmaceutically formulated angiotensin (1-7) heptapeptide, identical to the endogenously produced, non-hypertensive derivative of angiotensin II (Ang II).<br>* Other names: Angiotensin-(1-7);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety of TXA127 in patients with DMD | Incidence of adverse events (AEs), their severity and relationship to treatment | 6 months plus 12 month extension | 
| To evaluate the effects of treatment on ejection fraction (EF) | Percent change in EF, as measured by echocardiogram (ECHO); Absolute change in EF, as measured by echocardiogram | 6 months plus 12 month extension | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effects of treatment on upper extremity muscle function | Percent change in upper extremity strength, as measured by grip strength with a dynamometer; Absolute change in upper extremity strength, as measured by grip strength with a dynamometer | 6 months plus 12 month extension | 
| To evaluate the effects of treatment on fractional shortening (FS) | Percent and absolute change in fractional shortening as measured by echocardiogram | 6 months plus 12 month extension |