Gene Therapy (AT132) for Myotubular Myopathy

(ASPIRO Trial)

Recruiting at 5 trial locations

Age: < 18

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: Astellas Gene Therapies

Must not be taking: Pyridostigmine, Immune-modulating agents

Disqualifiers: Premature birth, Liver disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

27 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if participants must stop taking their current medications. However, participants must not have taken pyridostigmine or any medication to treat XLMTM within 3 months before the trial starts, and any other medications for chronic conditions must be stable for at least 4 weeks before dosing.

What data supports the effectiveness of the treatment AT132 for Myotubular Myopathy?

Research shows that gene therapy using AAV vectors to deliver myotubularin, the protein missing in myotubular myopathy, improves muscle strength and prolongs survival in animal models. This suggests that similar gene therapy approaches, like AT132, could be effective in treating this condition. ^{1 2 3 4 5}

Is gene therapy (AT132) for myotubular myopathy safe in humans?

In animal studies, gene therapy using AAV vectors for myotubular myopathy showed no signs of toxicity or harmful immune responses, suggesting it may be safe for future human trials. ^{1 3 4 6 7}

How is the treatment AT132 for myotubular myopathy different from other treatments?

AT132 is a gene therapy that uses an adeno-associated virus (AAV) vector to deliver a functional copy of the MTM1 gene directly to muscle cells, aiming to correct the underlying genetic defect causing myotubular myopathy. This approach is unique because it targets the root cause of the disease, unlike other treatments that may only address symptoms. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests AT132, a gene therapy, in children under 5 with a rare muscle disease. The therapy aims to deliver a healthy gene to improve muscle function. Participants will receive one dose and be monitored for safety and effectiveness over several years. AT132 has been used in previous gene therapy trials for muscle diseases.

Research Team

Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Eligibility Criteria

This trial is for boys under 5 with X-Linked Myotubular Myopathy (XLMTM) confirmed by a specific gene mutation. They must need breathing support, weigh over 4.8 kg in France, and have no recent surgeries or infections. Those with heart issues, anemia, liver disease, or certain medication use are excluded.

Inclusion Criteria

I am male.

UNIQUE to France: Subject's weight is ≥ 4.8 kg

I am using or open to using a cuffed tracheostomy tube for breathing assessments.

Exclusion Criteria

You have a high level of AAV8 neutralizing antibodies in your blood.

I have a serious liver condition.

I have had or will have scoliosis surgery within a year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Small groups of young children were given different doses of AT132 to determine the best dose for treating the muscle disease.

24 weeks

Multiple visits for dose administration and monitoring

Pivotal Expansion

Participants were enrolled to confirm the safety and efficacy of resamirigene bilparvovec at a specific dose.

24 weeks

Regular visits for safety and efficacy assessments

Long-term Follow-up

Participants are monitored for safety and muscle function improvements over a long period after receiving AT132.

10 years

Annual visits for safety and muscle function assessments

Treatment Details

Interventions

• AT132

Trial Overview The study tests AT132's safety and effectiveness in treating XLMTM. Participants receive one dose of AT132 and are monitored for ten years. It's multinational with ascending doses compared to delayed treatment controls.

Participant Groups

Group I: 3.5 × 10^14 vg/kg (High dose) Experimental Treatment 1 Intervention

Participants received 3.5 × 10\^14 vg/kg of body weight resamirigene bilparvovec as a single dose intravenously on Day 1. A sentinel dose was given to first participant and if there were no safety concerns, subsequent participants received either resamirigene bilparvovec at the same dose or control with delayed treatment after at least 4 weeks of post-dose data from the sentinel participant.

Group II: 1.3 × 10^14 vg/kg (Low dose) Experimental Treatment 1 Intervention

Participants received 1.3 x 10\^14 viral genomes per kilogram (vg/kg) of body weight resamirigene bilparvovec as a single dose intravenously on Day 1. A sentinel dose was given to first participant and if there were no safety concerns, subsequent participants received either resamirigene bilparvovec at the same dose or control with delayed treatment after at least 4 weeks of post-dose data from the sentinel participant.

Who Is Running the Clinical Trial?

Astellas Gene Therapies

Lead Sponsor

Trials

7

Recruited

400+

Audentes Therapeutics

Lead Sponsor

Trials

8

Recruited

270+

References

1. United States pubmed.ncbi.nlm.nih.gov

Gene therapy prolongs survival and restores function in murine and canine models of myotubular myopathy. [2021]

2. England pubmed.ncbi.nlm.nih.gov

AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Intravenous Administration of a MTMR2-Encoding AAV Vector Ameliorates the Phenotype of Myotubular Myopathy in Mice. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Single Intramuscular Injection of AAV-shRNA Reduces DNM2 and Prevents Myotubular Myopathy in Mice. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Spectrum of Clinical Features in X-Linked Myotubular Myopathy Carriers: An International Questionnaire Study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Systemic AAV8-Mediated Gene Therapy Drives Whole-Body Correction of Myotubular Myopathy in Dogs. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Antisense oligonucleotide-mediated Dnm2 knockdown prevents and reverts myotubular myopathy in mice. [2018]