- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06013839
TXA127 in 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 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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Richard L Franklin, MD, PhD
- Phone Number: 101 1-617-245-0289
- Email: rfranklin@constanttherapeutics.com
Study Contact Backup
- Name: Elizabeth Wagner, MS, MBA
- Phone Number: 102 1-617-245-0289
- Email: ewagner@constanttherapeutics.com
Study Locations
-
-
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Jerusalem, Israel
- Recruiting
- Hadassah Medical Center
-
Contact:
- Talia Dor, MD
-
Principal Investigator:
- Talia Dor, MD
-
Ramat Gan, Israel
- Recruiting
- Sheba Medical Center
-
Contact:
- Amir Dori, MD, PhD
-
Principal Investigator:
- Amir Dori, MD, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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:
- For a patient ≤ 20 years of age, EF > 35% and < 55% and fractional shortening of ≤ 28% at the time of screening.
- For a patient > 20 years of age, EF > 20% and fractional shortening ≤ 28% at the time of screening.
Reproducible (+/- 10%) difference between screening and baseline of percent predicted FVC , using the best out of 3 efforts at each visit:
- 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.
- 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).
- 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)
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: TXA127 SC 0.5mg/kg/day
TXA127 (talfirastide) 0.5mg/kg/day given via subcutaneous injection for 6 months
|
TXA127 (talfirastide) is a pharmaceutically formulated angiotensin (1-7) heptapeptide, identical to the endogenously produced, non-hypertensive derivative of angiotensin II (Ang II).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To evaluate the safety of TXA127 in patients with DMD
Time Frame: 6 months plus 12 month extension
|
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)
Time Frame: 6 months plus 12 month extension
|
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
Time Frame: 6 months plus 12 month extension
|
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)
Time Frame: 6 months plus 12 month extension
|
Percent and absolute change in fractional shortening as measured by echocardiogram
|
6 months plus 12 month extension
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To evaluate the effects of treatment on exploratory DMD-related clinical signs, FVC
Time Frame: 6 months plus 12 month extension
|
Forced Vital Capacity (FVC) % predicted Absolute and percent (where applicable) change in the following biomarkers in the blood:
|
6 months plus 12 month extension
|
To evaluate the effects of treatment on exploratory DMD-related clinical signs, PEF
Time Frame: 6 months plus 12 month extension
|
Peak Expiratory Flow (PEF) % predicted (if available) Absolute and percent (where applicable) change in the following biomarkers in the blood:
|
6 months plus 12 month extension
|
To evaluate the effects of treatment on exploratory DMD-related biomarkers, Troponin
Time Frame: 6 months plus 12 month extension
|
Absolute and percent (where applicable) change in Troponin
|
6 months plus 12 month extension
|
To evaluate the effects of treatment on exploratory DMD-related biomarkers, BNP
Time Frame: 6 months plus 12 month extension
|
Absolute and percent (where applicable) change in Brain Natriuretic Peptide (BNP)
|
6 months plus 12 month extension
|
To evaluate the effects of treatment on exploratory DMD-related biomarkers, BDNF
Time Frame: 6 months plus 12 month extension
|
Absolute and percent (where applicable) change in Brain-derived neurotrophic factor (BDNF)
|
6 months plus 12 month extension
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Richard L Franklin, MD, PhD, Constant Therapeutics LLC
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- TXA127-DMD-002
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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