Study of ASP2957 in Male Participants With X-linked Myotubular Myopathy Who Need Ventilators

NCT07052929 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2957-CL-01012025-523213-29
• Study Type: interventional
• Target: 9
• Locations: 2 countries
• Sites: 4

Brief Summary

X-linked myotubular myopathy (XLMTM) is a rare and serious condition present at birth where the muscles do not work properly. There are currently no approved therapies for XLMTM. The protein myotubularin is needed for muscle development, movement and breathing. A gene called MTM1 tells the body to make myotubularin. XLMTM is caused by changes, or mutations, in the MTM1 gene. Changes in the MTM1 gene cause low or no levels of myotubularin to be made, so the muscles do not work properly. Gene therapy is a way of getting a healthy copy of a gene into the body. This allows the body's cells to make a normal protein that may reduce disease symptoms. Researchers have developed ASP2957 to get a healthy MTM1 gene into the body. This could help improve muscle development and function in young children with XLMTM. In this study, ASP2957 will be given to humans for the first time. ASP2957 has the healthy MTM1 gene inside a type of empty (killed) virus. The virus delivers the healthy MTM1 gene directly into cells in the body. It's possible that some boys may have antibodies to the virus if they have previously been infected with a similar virus. The antibodies could stop ASP2957 from working properly and cause an immune reaction to ASP2957. To prevent this, the boys will also be given medicines to lower the immune system. The main aims of this study are to check the safety of ASP2957, how well it is tolerated, and to find a suitable dose of ASP2957. The study was designed in 2 phases. In Phase 1, different small groups of boys will receive lower to higher doses of ASP2957. Each boy will receive a single infusion of ASP2957. Any medical problems will be recorded for each dose. This is done to find a suitable dose of ASP2957 to use in Phase 2. In Phase 2, another small group of young boys will receive a single infusion of ASP2957. The most suitable dose of ASP2957 worked out from Phase 1 will be used. The boys will be checked for up to 1 year after their single infusion of ASP2957. After this, there will be the option for the boys to join another study so they will continue to be checked longer term.

Conditions

X-Linked Myotubular Myopathy

Keywords

XLMTM; Recombinant Adeno-Associated Virus

Outcome Measures

Primary Outcomes (8)

• Number of participants with treatment emergent adverse events (TEAEs)

  An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of study intervention. This includes events related to the comparator, if applicable, and events related to the (study) procedures. A TEAE is defined as an AE observed after administration of ASP2957.

  Up to week 52

• Number of participants with adverse events of special interest (AESIs)

  AESIs include myocardial-associated events, muscle abnormalities, hepatobiliary disorders, thrombocytopenia, TMA and life-threatening infections.

  Up to week 52

• Number of participants with laboratory value abnormalities and/or adverse events (AEs)

  Number of participants with potentially clinically significant laboratory values.

  Up to 52 weeks

• Number of participants with electrocardiogram (ECG) abnormalities and/or AEs

  Number of participants with potentially clinically significant ECGs.

  Up to 52 weeks

• Number of participants with echocardiogram (ECHO) abnormalities and/or AEs

  Number of participants with potentially clinically significant ECHOs.

  Up to 52 weeks

• Number of participants with muscle magnetic resonance imaging (MRI) abnormalities and/or AEs

  Number of participants with potentially clinically significant muscle MRIs.

  Up to 52 weeks

• Number of participants with histopathology abnormalities and/or AEs from muscle biopsy

  Number of participants with potentially clinically significant histopathology from muscle biopsy.

  Up to 52 weeks

• Number of participants with physical examinations abnormalities and/or AEs

  Number of participants with potentially clinically significant physical examinations.

  Up to 52 weeks

Secondary Outcomes (9)

• Change from baseline in hours per day of ventilation support at week 52

  Baseline and up to week 52

• ASP2957 vector deoxyribonucleic acid (DNA) in serum through week 52

  Up to week 52

• ASP2957 vector DNA in muscle biopsy at week 52

  Week 52

• ASP2957 vector DNA in saliva

  Up to week 52

• ASP2957 vector DNA in urine

  Up to week 52

Study Arms (2)

Part 1 : ASP2957 Dose Escalation

EXPERIMENTAL

Participants will receive sequential dose levels of a single infusion of ASP2957 and immunosuppression prophylaxis including methylprednisolone, prednisolone and sirolimus.

Genetic: ASP2957; Drug: Methylprednisolone; Drug: Prednisolone; Drug: Sirolimus

Part 2: ASP2957 Dose Expansion

EXPERIMENTAL

Participants will receive a single infusion of ASP2957 (dose selected in Part 1) and immunosuppression prophylaxis including methylprednisolone, prednisolone and sirolimus.

Genetic: ASP2957; Drug: Methylprednisolone; Drug: Prednisolone; Drug: Sirolimus

Interventions

ASP2957 GENETIC

Intravenous infusion

Also known as: MyoAAV3.8 engineered capsid - myosin heavy chain kinase 7 - human myotubularin (MyoAAV3.8-MHCK7-hMTM1)

Part 1 : ASP2957 Dose Escalation; Part 2: ASP2957 Dose Expansion

Methylprednisolone DRUG

Intravenous infusion

Part 1 : ASP2957 Dose Escalation; Part 2: ASP2957 Dose Expansion

Prednisolone DRUG

Route of administration based on locally sourced product

Part 1 : ASP2957 Dose Escalation; Part 2: ASP2957 Dose Expansion

Sirolimus DRUG

Route of administration based on locally sourced product

Part 1 : ASP2957 Dose Escalation; Part 2: ASP2957 Dose Expansion

Eligibility Criteria

• Age: Up to 36 Months
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant is projected to be ≤ 36 months of age at dosing.
• 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 American College of Medical Genetics (ACMG) standards and guidelines for interpretation of sequence variants. Although samples will be sent to the sponsor central laboratory during screening for exploratory testing, results of this testing are not required for enrollment.
• Participant is ventilator-dependent and meets the following criteria:
• Required respiratory support at birth
• Requires ≥ 20 hours per day of invasive ventilator support (confirmed during screening)
• Has a tracheostomy tube
• Participant has no evidence of hepatic peliosis, increased echogenicity or any other clinically important abnormal finding on liver ultrasound.
• Participant can receive immunosuppression per protocol.
• Participant's hepatobiliary laboratory measurements must meet the criteria during screening and for the 2-month retrospective assessment of participant's medical history from the time of signing the ICF:
• Participant's hematological laboratory measurements must meet the criteria during screening:
• Participant's parent(s) or legally authorized representative LAR(s) must provide documentation of being current with recommended immunization schedule according to regional guidelines.
• If any immunization has not been administered, the medical reasons must be documented by the investigator along with medical risk associated with ASP2957 and immunosuppression administration. The sponsor will review the risk assessment with the investigator and determine the participant's eligibility for the study.
• Immunization of household contacts can be considered based on regional standards of care of individuals receiving immunosuppression regimens.
• Participant and participant's parent(s) or LAR(s) are willing and able to comply with study visits and study procedures.
• Participant's parent(s) or LAR(s) agree that the participant will not participate in another interventional study from the time of signing the Informed Consent Form (ICF) through week 52.

You may not qualify if:

• Participant born \< 35 weeks gestation is still not term as per corrected age.
• Participant is nutritionally unstable with weight less than fifth percentile for age or has a vitamin A, E or K deficiency.
• Participant requires supplemental oxygen on a routine or chronic basis.
• Participant currently has a clinically important respiratory infection or other clinically important active infection of any kind.
• Participant has an active viral or bacterial infection including, but not limited to, positive testing for the following:
• tuberculosis (TB) using the QuantiFERON-TB test
• Active hepatitis A virus (HAV), hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Prior HBV or HCV virus infection due to the risk of reactivation associated with immunosuppression
• human immunodeficiency virus type 1 (HIV-1) and human immunodeficiency virus type 2 (HIV-2)
• coronavirus disease 2019 (COVID-19)
• cytomegalovirus (CMV), viral loads ≥ 500 IU/mL or attributable symptoms or evidence of end-organ disease due to CMV.
• 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.
• Participant has prior history of abnormal transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST)) and/or abnormal bilirubin metabolism associated with ascites, jaundice (aside from neonatal hyperbilirubinemia) or gastrointestinal bleeding.
• Participant has a significant medical condition or life-threatening disease other than XLMTM that would interfere with adhering to protocol requirements or would increase the risk of immunosuppression and/or recombinant adeno-associated virus (rAAV) administration.
• Participant has musculoskeletal complications such as severe contractures and/or scoliosis that would limit the ability to observe improvements in neuromuscular function.

Sponsors & Collaborators

• Astellas Gene Therapies: lead

Study Sites (4)

Lurie Children's Hospital

Chicago, Illinois, 60611, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

The Hospital for Sick Children

Toronto, Ontario, Canada

RECRUITING

MeSH Terms

Conditions

Myopathies, Structural, Congenital

Interventions

Methylprednisolone; Prednisolone; Sirolimus

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Macrolides; Lactones; Organic Chemicals

Study Officials

• Medical Director

  Astellas Gene Therapies

  STUDY DIRECTOR

Central Study Contacts

Astellas Gene Therapies

CONTACT

800-888-7704; Astellas.registration@astellas.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2025
• First Posted: July 8, 2025
• Study Start: December 15, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (3)