DMD-Associated Dilated CardiomyopathyPhase 2NCT06013839
TXA127 in Non-Ambulant Patients With DMD Cardiomyopathy
A Phase 2 study testing talfirastide in people with DMD-Associated Dilated Cardiomyopathy, run by Constant Therapeutics LLC at 2 sites in Israel.
Trial summary
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: 1. 6-month open-label treatment phase: Male DMD patients with documented cardiomyopathy, will receive a daily subcutaneous injection of TXA127 0.5… Read more about this study
- Who is it for?
- Ages 16 years and older, men only
- Conditions the study is for
- DMD-Associated Dilated Cardiomyopathy
- What is being tested?
- talfirastide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesIsrael
- Study dates
- 31 Aug 2023to Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
2 sites in 1 country.
Israel2 sites, 2 recruiting
- Recruiting
Hadassah Medical Center
Jerusalem
Talia Dor, MD
Talia Dor, MD
- Recruiting
Sheba Medical Center
Ramat Gan
Amir Dori, MD, PhD
Amir Dori, MD, PhD
About this study
Official title: 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.
- Conditions
- DMD-Associated Dilated Cardiomyopathy
- Being tested
- talfirastide
- Medical subject headings
- Dmd-Associated Dilated Cardiomyopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
talfirastideDrug
Also called TXA127, Angiotensin-(1-7)
TXA127 (talfirastide) is a pharmaceutically formulated angiotensin (1-7) heptapeptide, identical to the endogenously produced, non-hypertensive derivative of angiotensin II (Ang II).
| Study group | Role | What they receive |
|---|---|---|
| TXA127 SC 0.5mg/kg/day | Experimental | TXA127 (talfirastide) 0.5mg/kg/day given via subcutaneous injection for 6 months Receives: Drug: talfirastide |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety of TXA127 in patients with DMD
Incidence of adverse events (AEs), their severity and relationship to treatment
Measured: 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
Measured: 6 months plus 12 month extension
Secondary outcomes (2)
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
Measured: 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
Measured: 6 months plus 12 month extension
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2023
- Study start31 Aug 2023
- Primary completionAug 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DMD-Associated Dilated CardiomyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Constant Therapeutics LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Richard L Franklin, MD, PhD, Study chair, Constant Therapeutics LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06013839
- Sponsor's protocol ID
- TXA127-DMD-002
- Status last verified
- Sep 2023
- First submitted
- 16 Aug 2023
- Last updated
- 23 Jan 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06013839
- Acronym / sponsor ID
- TXA127-DMD-002
- Conditions
- DMD-Associated Dilated Cardiomyopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Constant Therapeutics LLCIndustry (pharma, biotech, devices)
- Study start
- 31 Aug 2023 (actual)
- Primary completion
- Aug 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 28 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TXA127 SC 0.5mg/kg/day | Experimental | Drug: talfirastideTXA127 (talfirastide) 0.5mg/kg/day given via subcutaneous injection for 6 months |
Who may qualify
- Ages
- 16 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
- Reproducible (+/- 10%) difference between screening and baseline of percent predicted FVC , using the best out of 3 efforts at each visit:
- Subjects must be taking systemic glucocorticoids for at least six months prior to screening.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| talfirastideAlso: TXA127, Angiotensin-(1-7)TXA127 (talfirastide) is a pharmaceutically formulated angiotensin (1-7) heptapeptide, identical to the endogenously produced, non-hypertensive derivative of angiotensin II (Ang II). | Drug | TXA127 SC 0.5mg/kg/day |
Primary outcome
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
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
2 secondary outcomes
To evaluate the effects of treatment on upper extremity muscle function
Time frame: 6 months plus 12 month extension
To evaluate the effects of treatment on fractional shortening (FS)
Time frame: 6 months plus 12 month extension
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard L Franklin, MD, PhD study chair
Constant Therapeutics LLC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing talfirastide in people with DMD-Associated Dilated Cardiomyopathy, run by Constant Therapeutics LLC at 2 sites in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Richard L Franklin, MD, PhD (1-617-245-0289 ext. 101, rfranklin@constanttherapeutics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the safety of TXA127 in patients with DMD (time frame: 6 months plus 12 month extension). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2024.