Clinical Trial in Patients With Barth Syndrome- 4TAZPower (4TAZPower)

Phase 3b/4, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Trial to Evaluate the Efficacy and Safety of Daily Subcutaneous Injections of Elamipretide in Patients With Genetically Confirmed Barth Syndrome

Phase 3b/4, randomized, double-blind, parallel-group, placebo-controlled clinical trial to evaluate the efficacy, safety, and pharmacokinetics of a once daily SC injection of elamipretide in subjects with genetically confirmed BTHS for 72 weeks. The primary trial objective is to confirm the efficacy of elamipretide which is approved in the United States(FORZINITY™) under the accelerated approval based on an improvement in knee extensor muscle strength, an intermediate clinical endpoint.

Study Overview

• Status: Not yet recruiting
• Conditions: Barth Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Elamipretide

Detailed Description

The SPIBA-401 trial is a post marketing Phase 3b/4, randomized, double-blind, parallel-group, placebo-controlled clinical trial to evaluate the efficacy, safety, and pharmacokinetics of a once daily subcutaneous (SC) injection of elamipretide in subjects with genetically confirmed Barth syndrome (BTHS) for 72 weeks. The primary trial objective is to confirm the efficacy of elamipretide which is approved in the United States under the name FORZINITY™ as a mitochondrial cardiolipin binder indicated to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg. This indication is approved in the United States under accelerated approval based on an improvement in knee extensor muscle strength, an intermediate clinical endpoint.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Rekha Sathyanarayana; Phone Number: 617-762-2579; Email: rekha.sathyanarayana@stealthbt.com
• Study Contact Backup: Name: Lani Glennon; Email: lani.glennon@parexel.com

Study Locations

• United Kingdom
  • Bristol, United Kingdom
    • Bristol Royal Hospital for Children Upper Maudlin Street Paul O'Gorman Building
    • Contact: Ros Strang; Phone Number: 0+44 1173 429210; Email: rosalind.strang@uhbw.nhs.uk
• United States
  • Massachusetts
    • Needham, Massachusetts, United States, 02494
      • Trial Not Offered in the U.S

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Willing and able to provide signed informed consent form (ICF) prior to participation in any trial-related procedures. If applicable, informed consent in writing from parent(s) or legally-acceptable representative(s) and, informed assent from subject (if age appropriate according to local requirements) should be provided.
2. Agrees to adhere to the trial requirements for the length of the trial.
3. Must have genetically confirmed Barth Syndrome (pathogenic variant in the TAZ gene)
4. Male aged ≥ 5 years at time of the Screening Visit
5. Left Ventricular Ejection fraction of ≥ 50% by 3-D Echocardiogram at the Screening Visit.
6. For subjects with a medical history of cardiomyopathy, must be on a stable regimen (unchanged and constant) of background heart failure medications for at least 3 months prior to the Screening Visit.
7. Able to administer Investigational Medicinal Product (IMP) or have an appropriate designee who can administer the IMP (i.e., a capable family member or a caregiver).
8. Subjects with female partners of childbearing potential must be willing to use a highly effective method of contraception (e.g., abstinence, dual method of contraception) from the date they sign the ICF until 28 days after the last dose of IMP.

Key Exclusion Criteria:

1. Unable to perform the required functional tests or undergo echocardiography.
2. History of solid organ transplant, except successful cardiac transplantation > 12 months prior to screening, if, in the opinion of the Investigator, there is no evidence of organ rejection and post-transplant pharmacotherapy, is stable, and does not pose additional safety risk to participant.
3. Patients with an implantable cardioverter defibrillator (ICD) and with a known occurrence of ICD discharge in the 3 months prior to the Screening Visit.
4. Current placement on the waiting list for heart transplantation.
5. Hospitalization for heart failure within 6 months prior to the Screening Visit.
6. Any disease or medical condition that in the opinion of the Investigator would prevent the subject from successfully participating in the trial and reliably completing the assessments or might confound trial results.
7. Has a history of a systemic eosinophilic illness
8. Estimated Glomerular Filtration Rate (eGFR) of < 30 mL/min at the Screening Visit (using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 formula for subjects >16 years of age and the Schwartz 2009 formula for subjects 5-16 years of age).
9. Active malignancy or any other cancer from which the subject has been cancer-free for < 2 years. Localized squamous or non-invasive basal cell skin carcinomas are allowed, if appropriately treated prior to Screening.
10. Participation in other investigational drug or device clinical trials within 30 days or 5 half-lives (whichever is longer) of Screening; or is currently enrolled in a non-interventional clinical trial that, in the opinion of the Investigator, may be potentially confounding to the results of the current trial.
11. History of allergic reaction to the IMP or any of its components.
12. Prior participation in any elamipretide trial or expanded access programs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Elamipretide; Elamipretide - aqueous, sterile 5.0 mL single-patient, ready to use, multi-dose glass vial containing 3.5 mL of elamipretide solution (elamipretide [80 mg/mL],	Drug: Elamipretide; sub cutaneous injection; Other Names: elamipretide hydrochloride
Placebo Comparator: Placebo; Matching Placebo-aqueous, sterile 5.0 mL single-patient, ready to use, multi-dose glass vial containing will be composed of 3.5mL of sodium chloride, phosphate buffer, and benzyl alcohol similar to excipients in active drug but without the active drug substance	Drug: Placebo; sub cutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Efficacy End Point	-change in the composite normalized score of the three functional tests: Six-minute walk test (6MWT), the triple-timed up and go test (3TUG), and the Five times sit-to-stand test (5XSST) from baseline to 72 weeks of treatment	72 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Efficacy End Point 1	- Change in 6Minute Walk Test from Baseline to Week 72	72 weeks
Secondary Efficacy End Point 2	-Change in 3Timed Up and Go Test from Baseline to Week 72	72 weeks
Secondary Efficacy End Point 3	-Change in 5XSit to Stand Test from Baseline to Week 72	72 weeks
Secondary Efficacy End Point 4	-Change in Patient Global Impression of Severity Scale (PGI-S) score from Baseline to Week 72	72 weeks
Secondary Efficacy End Point 5	Change in Clinician Global Impression of Severity Scale (CGI-S) score from Baseline to Week 72	72 weeks
Secondary Efficacy End Point	Change in knee extensor muscle strength as measured by handheld dynamometry (HHD)from Baseline to Week 72	72 weeks
Secondary Efficacy End Point 6	-Change in hip flexor muscle strength as measured by HHD from Baseline to Week 72	72 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety End Point Adverse Event Reporting	-Report the # of subjects with adverse events and incidence and severity of such adverse events (AEs)	72weeks

Collaborators and Investigators

• Sponsor: Stealth BioTherapeutics Inc.
• Investigators: Study Director: Rekha Sathyanarayana, Stealth BioTherapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): November 30, 2029

Study Registration Dates

• First Submitted: March 12, 2026
• First Submitted That Met QC Criteria: April 8, 2026
• First Posted (Actual): April 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: BTHS; Ultra Rare X-Linked Mitochondrial Disorder; Genetic Defect in TAZ Gene
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Abnormalities, Multiple; Lipid Metabolism Disorders; Genetic Diseases, X-Linked; Lipid Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Barth Syndrome; arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide
• Other Study ID Numbers: SPIBA-401

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes