ASP2957 for Myotubular Myopathy

Overseen By Astellas Gene Therapies

Age: < 18

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Astellas Gene Therapies

Must be taking: Immunosuppressants

Must not be taking: Monoclonal antibodies

Disqualifiers: Respiratory infection, Hepatitis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

9 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new gene therapy, ASP2957, for boys with X-linked myotubular myopathy (XLMTM), a serious condition affecting muscle function. The trial will introduce a healthy MTM1 gene into the body to improve muscle development and breathing. Initially, the study will test different doses to find the safest and most effective amount, then monitor participants for up to a year. Boys who are ventilator-dependent and have a confirmed diagnosis of XLMTM may be suitable candidates for this trial. As a Phase 1, Phase 2 trial, participants will be among the first to receive this new treatment and help determine its effectiveness in improving muscle function.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking treatments for cholestasis, you must stop them at least 4 weeks before joining the study. Also, you should not have received systemic immunomodulating agents within 90 days before the trial starts.

Is there any evidence suggesting that ASP2957 is likely to be safe for humans?

Research shows that ASP2957 is undergoing its first safety tests in humans. This early-phase trial primarily examines treatment tolerance, with all potential side effects and reactions closely monitored. Young boys receive a single dose of ASP2957, along with medications to prevent immune reactions.

As an early-stage trial, limited information exists on treatment responses. However, the study is carefully designed to identify any medical issues, especially since the treatment uses a modified virus to deliver a gene. The goal is to determine a dose that is both effective and safe. Participants will be monitored for up to a year to assess any long-term effects, ensuring the treatment's safety before advancing to larger studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for myotubular myopathy, which mainly focus on managing symptoms and providing supportive care, ASP2957 offers a new approach by potentially addressing the underlying cause of the disease. Researchers are excited because ASP2957 is designed to work at the genetic level, aiming to correct the faulty gene responsible for the condition. This method could lead to more substantial and lasting improvements in muscle function compared to existing treatments. Additionally, the use of immunosuppression prophylaxis alongside ASP2957 helps ensure the treatment is safely tolerated, which is a crucial step toward making this innovative therapy viable for patients.

What evidence suggests that ASP2957 might be an effective treatment for myotubular myopathy?

Research has shown that ASP2957 aims to help with X-linked myotubular myopathy (XLMTM) by providing a healthy version of the MTM1 gene. This gene is crucial because it produces myotubularin, a protein essential for proper muscle function. The goal is for the body to produce this protein correctly, potentially improving muscle strength and breathing in affected children. Early results from similar gene therapies have been promising in treating genetic muscle disorders. Although ASP2957 is being tested in humans for the first time, other studies have successfully replaced faulty genes. Participants in this trial will receive ASP2957 in two parts: Part 1 involves dose escalation, and Part 2 involves dose expansion, both with immunosuppression prophylaxis. ^{1 2 3 4 5}

Who Is on the Research Team?

Medical Director

Principal Investigator

Astellas Gene Therapies

Are You a Good Fit for This Trial?

This trial is for boys ≤ 3 years old with X-linked myotubular myopathy (XLMTM) who need ventilators over 20 hours a day and have a tracheostomy tube. They must have a confirmed genetic diagnosis of XLMTM, no significant liver issues, be able to receive immunosuppression, and be up-to-date on vaccinations.

Inclusion Criteria

My genetic test shows I have a specific gene mutation linked to my condition.

I am, or my child is, under 3 years old at the time of treatment.

I needed help breathing when I was born.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive sequential dose levels of a single infusion of ASP2957 and immunosuppression prophylaxis

Varies per participant

Multiple visits for dose administration and monitoring

Dose Expansion

Participants receive a single infusion of ASP2957 at the dose selected in Part 1 with immunosuppression prophylaxis

Single infusion

Single visit for infusion, followed by monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

Regular monitoring visits up to 1 year

Open-label extension (optional)

Participants may opt into continuation of monitoring in another study for long-term follow-up

What Are the Treatments Tested in This Trial?

Interventions

• ASP2957

Trial Overview The study tests ASP2957, which carries a healthy MTM1 gene into the body using an empty virus to improve muscle function in XLMTM. It includes two phases: Phase 1 finds the right dose by giving different amounts to small groups; Phase 2 uses that dose in another group.

How Is the Trial Designed?

Group I: Part 2: ASP2957 Dose Expansion Experimental Treatment 4 Interventions

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

Group II: Part 1 : ASP2957 Dose Escalation Experimental Treatment 4 Interventions

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

Who Is Running the Clinical Trial?

Astellas Gene Therapies

Lead Sponsor

Trials

7

Recruited

400+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07052929

Study of ASP2957 in Male Participants With X-linked ... X-linked myotubular myopathy (XLMTM) is a rare and serious condition present at birth where the muscles do not work properly.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0960896625005826

74PDesign of a phase 1/2 study assessing the safety and ... 74PDesign of a phase 1/2 study assessing the safety and preliminary efficacy of ASP2957 gene therapy for X-linked myotubular myopathy (XLMTM). Author links ...

3. clinicaltrials.astellas.com clinicaltrials.astellas.com/study/2957-CL-0101

Study of ASP2957 in male participants with X-linked ... X-linked myotubular myopathy (XLMTM) is a rare and serious condition present at birth where the muscles do not work properly.

4. myotubulartrust.org myotubulartrust.org/research/clinical-trials/

Clinical Trials The first myotubular myopathy patient was dosed in September 2017 and preliminary results published in January 2018 and October 2019 were very encouraging.

5. withpower.com withpower.com/trial/phase-2-x-linked-myotubular-myopathy-6-2025-7130b

ASP2957 for Myotubular Myopathy This Phase 1 & 2 medical study run by Astellas Gene Therapies is evaluating whether ASP2957 will have tolerable side effects & efficacy for patients with ...