Study of ASP2957 in Male Patients with X-linked Myotubular Myopathy Who Need Ventilators

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astellas Gene Therapies Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Decision date (initial)

2026-02-09

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Astellas Pharma Gobal Development, Inc.

External identifiers

EU CT number

2025-523213-29-00

ClinicalTrials.gov

NCT07052929

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Dose response, Pharmacogenomic, Therapy

To evaluate the safety and tolerability of ASP2957 and to determine the recommended dose level

Secondary objectives 3

1. To evaluate the effect of ASP2957 on ventilation support
2. To evaluate biodistribution and vector shedding (excretion/secretion) after ASP2957 dosing
3. To evaluate the immunogenicity of ASP2957

Conditions and MedDRA coding

X-linked myotubular myopathy

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

IPD plan description

Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Participant is projected to be ≤ 36 months of age at dosing
2. 2. Participant has molecular genetic report from a CAP-approved testing facility at screening that confirms a diagnosis of XLMTM and harbors a “pathogenic” or “likely pathogenic” variant in the MTM1 gene as classified using the ACMG standards and guidelines for interpretation of sequence variants
3. 3. Participant is ventilator-dependent and meets the following criteria: a. Required respiratory support at birth b. Requires ≥ 20 hours per day of invasive ventilator support (confirmed during screening) c. Has a tracheostomy tube
4. 4. Participant has no evidence of hepatic peliosis, increased echogenicity or any other clinically important abnormal finding on liver ultrasound as assessed by the investigator in consultation with the site hepatologist
5. 5. Participant’s hepatobiliary laboratory measurements must meet the following criteria during screening and for the 2-month retrospective assessment of participant’s medical history: a. a. ALT and AST < 3 × ULN b. Direct bilirubin ≤ 1 × ULN c. Serum total bile acids < 2 × ULN, independent of fasting status
6. 6. Participant’s parent(s) or LAR(s) must provide documentation of being current with recommended immunization schedule according to regional guidelines.

Exclusion criteria 10

1. 1. Participant born < 35 weeks gestation is still not term as per corrected age.
2. 2. Participant is nutritionally unstable with weight less than fifth percentile for age or has a vitamin A, E or K deficiency.
3. 3. Participant requires supplemental oxygen on a routine or chronic basis. a. Note: The use of supplemental oxygen for acute, self-limited illnesses (for example, during hospitalization for pneumonia) shall not be exclusionary, provided the participant is neither acutely ill nor using supplemental oxygen at the time of screening.
4. 4. Participant currently has a clinically important respiratory infection or other clinically important active infection of any kind.
5. 5. Participant has an active viral or bacterial infection including, but not limited to, positive testing for: a. TB using the QuantiFERON-TB test b. Active HAV, HBV or HCV c. Prior HBV or HCV virus infection due to the risk of reactivation associated with immunosuppression d. HIV-1 and HIV-2 e. COVID-19 f. CMV, viral loads ≥ 500 IU/mL or attributable symptoms or evidence of end-organ disease due to CMV.
6. 6. Participant has any history of cholestatic liver dysfunction and/or treatment for cholestasis. If the participant is taking prophylactic treatment for cholestasis (e.g., ursodiol, cholestyramine, rifampin or other therapies) which has not been prescribed for cholestatic liver dysfunction, treatment must be discontinued for at least 4 weeks prior to signing the ICF. a. Neonatal hyperbilirubinemia resolving within 4 weeks of birth in a full-term infant is not an exclusion.
7. 7. Participant has prior history of abnormal transaminases (ALT or AST) and/or abnormal bilirubin metabolism associated with ascites, jaundice (aside from neonatal hyperbilirubinemia) or gastrointestinal bleeding.
8. 8. Other than as required per protocol, participant has received or plans to receive systemic immunomodulating agents within 90 days before day 1 (use of inhaled corticosteroids to manage chronic respiratory conditions is allowed).
9. 9. Participant received any treatment for cholestasis (e.g., ursodiol, cholestyramine, rifampin or other therapies) prior to signing the ICF.
10. 10. Participant tests positive for anti-MyoAAV3.8 TAb, as determined by central laboratory testing. a. Note: Since very young children may have passive antibodies transferred in utero from the mother, participants ≤ 6 months of age who initially test positive for anti- MyoAAV3.8 TAb may be rescreened for study eligibility.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence and severity of TEAEs and AESIs
2. Change from baseline in the following safety assessments through week 52: o clinical laboratory tests o cardiac findings from ECG and ECHO o muscle findings from muscle MRI and histopathology o physical examinations

Secondary endpoints 5

1. Change from baseline in hours per day of ventilation support at week 52
2. ASP2957 vector DNA in serum through week 52
3. ASP2957 vector DNA in muscle biopsy at week 52
4. ASP2957 vector DNA in saliva, urine and stool
5. Immunogenicity of ASP2957 through week 52 as assessed with the following tests: o Anti-MyoAAV3.8 TAb and NAb o Anti-myotubularin Tab

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astellas Gene Therapies Inc.

Sponsor organisation

Astellas Gene Therapies Inc.

Address

480 Forbes Boulevard

City

South San Francisco

Postcode

94080-2015

Country

United States

Scientific contact point

Organisation

Astellas Gene Therapies Inc.

Contact name

RA Clinical Trial Unit Head

Public contact point

Organisation

Astellas Gene Therapies Inc.

Contact name

RA Clinical Trial Unit Head

Third parties 14

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications