Gene Transfer Clinical Study in X-Linked Myotubular Myopathy

• Register: ClinicalTrials.gov
• Last refreshed on: 8 January 2024
• Main ID: NCT03199469
• Date of registration: 21/06/2017
• Prospective Registration: Yes
• Primary sponsor: Astellas Gene Therapies
• Public title: Gene Transfer Clinical Study in X-Linked Myotubular Myopathy ASPIRO
• Scientific title: ASPIRO: A Phase 1/2/3, Randomized, Open-Label, Ascending-Dose, Delayed-Treatment Concurrent Control Clinical Study to Evaluate the Safety and Efficacy of AT132, an AAV8-Delivered Gene Therapy in X-Linked Myotubular Myopathy (XLMTM) Patients
• Date of first enrolment: August 2, 2017
• Target sample size: 26
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03199469
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2/Phase 3

Countries of recruitment

Canada, France, Germany, United States

Contacts

• Name: Medical Director
• Affiliation: Astellas Pharma Global Development, Inc.

Key inclusion & exclusion criteria

Inclusion Criteria:

- Subject has a diagnosis of XLMTM resulting from a genetically confirmed mutation in
the MTM1 gene as assessed by a Sponsor-approved testing facility.

- Subject is male.

- Subject is aged less than 5 years old at dosing

- Subject requires mechanical ventilatory support:

Part 1: Subject requires some mechanical ventilatory support (e.g., ranging from 24 hours
per day full time mechanical ventilation, to noninvasive support such as continuous
positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) during sleeping
hours).

Part 2: Subject requires invasive mechanical ventilatory support ranging from 20 - 24 hours
per day at screening (confirmed by daytime polysomnographic study).

- Subject requiring invasive mechanical ventilator support is fitted with or willing to
be fitted with a cuffed tracheostomy tube for some respiratory assessments.

- Subject has ventilator maximum positive end-expiratory pressure (PEEP) <8 cm H2O at
screening.

- UNIQUE to France: Subject's weight is = 4.8 kg.

Exclusion Criteria:

- Subject is participating in an interventional study designed to treat XLMTM.

- Subject born <35 weeks gestation who is still not term as per corrected age.

- Subject tests positive for AAV8 neutralizing antibody with titers above protocol
specified threshold.

- Subject had recent surgery (<3 months before Day 1) or has planned surgery that may
confound data collection during the first 48 weeks of the study.

- Subject has a clinically important condition other than XLMTM in the opinion of the
investigator.

- Subject has a clinically significant underlying liver disease.

- Subject is currently experiencing a clinically important respiratory infection or
other active infection.

- Subject has received pyridostigmine or any medication to treat XLMTM within 3 months
before Day 1.

- Other than as required per protocol, subject has received immune-modulating agents
within 3 months before Day 1 (use of inhaled corticosteroids to manage chronic
respiratory conditions is allowed); use of other concomitant medications to manage
chronic conditions must have been stable for at least 4 weeks before dosing.

- Subject has a contraindication to prednisolone.

- Subject has a contraindication to study drug or ingredients.

- Subject has previous scoliosis repair surgery/procedure, or planned/expected scoliosis
repair surgery/procedure in the 12 months following Day 1 (Part 2 including any
subjects enrolled under protocol v8 and beyond).

- Subject has contractures, scoliosis, or other medical condition that would limit the
potential to achieve unassisted sitting, in the opinion of the investigator (Part 2
including any subjects enrolled under protocol V8 and beyond).

- Subject is able to sit without assistance for at least 30 seconds at screening, in the
opinion of the investigator (Part 2 including any subjects enrolled under protocol V8
and beyond).

- Subject has a clinically important condition, including CTCAE v4.03 Grade = 2 anemia
(< 10 g/dL hemoglobin).

- Subject has a contraindication to ursodiol (ursodeoxycholic acid).

- UNIQUE to France: Subject has a prior diagnosis or history of cardiac arrhythmias,
myocarditis, or any other cardiac disease.

- UNIQUE to France: Subject has a contraindication to general anesthesia and to muscle
biopsy procedures.



Age minimum: N/A
Age maximum: 5 Years
Gender: Male

Health Condition(s) or Problem(s) studied

X-Linked Myotubular Myopathy

Intervention(s)

Genetic: AT132

Primary Outcome(s)

Change from baseline in hours of ventilation support at Week 24 [Time Frame: Baseline to Week 24]

Secondary Outcome(s)

Percentage of subjects achieving functionally independent sitting for at least 30 seconds by Week 24 [Time Frame: Up to Week 24]

Change from baseline in quantitative analysis of myotubularin expression in the muscle biopsy at Week 24 [Time Frame: Baseline to Week 24]

Change from baseline in maximal inspiratory pressure (MIP) at Week 24 [Time Frame: Baseline to Week 24]

Change from baseline in Pediatric Quality of Life Inventory (PedsQL) assessment at Week 24 [Time Frame: Baseline to Week 24]

Percentage of age-appropriate clinically relevant gross motor function milestones attained through Week 24 [Time Frame: Up to Week 24]

Time to reduction in required ventilator support to = 16 hours a day (only in subjects who require invasive ventilation) at Week 24 [Time Frame: Baseline to Week 24]

Change from baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) at Week 24 [Time Frame: Baseline to Week 24]

Change from baseline in quality of life Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) at Week 24 [Time Frame: Baseline to Week 24]

Percentage of subjects achieving full ventilator independence in the absence of acute illness and perioperatively at Week 24 [Time Frame: Week 24]

Survival [Time Frame: Up to Week 24]

Treatment-emergent adverse events (safety and tolerability) [Time Frame: Up to Month 120]

Secondary ID(s)

2017-000876-27

ATX-MTM-002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors