resamirigene bilparvovec for X-linked myotubular myopathy (XLMTM)

Inclusion criteria

• {"criterion_text":"- 1. Subject has a diagnosis of XLMTM resulting from a genetically confirmed mutation in the MTM1 gene as assessed by a Sponsor- approved testing facility.* * = Inclusion/exclusion criteria for delayed treatment control subjects before receiving AT132."}
• {"criterion_text":"- 2. Subject is male.*"}
• {"criterion_text":"- 3. Subject is aged less than 5 years old at dosing*"}
• {"criterion_text":"- 4. Subject requires mechanical ventilatory support: Part 1: Subject requires some mechanical ventilatory support (eg., 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 to 24 hours per day at screening (confirmed by daytime polysomnographic study)."}
• {"criterion_text":"- 5. Subject requiring invasive mechanical ventilator support is fitted with or willing to be fitted with a cuffed tracheostomy tube for some respiratory assessments.*"}
• {"criterion_text":"- 6. Subject has ventilator maximum positive end-expiratory pressure (PEEP) < 8 cm H2O at screening.*"}
• {"criterion_text":"- 7. Signed informed consent by the parent(s) or legally authorized representative(s) (LAR) (when applicable).*"}
• {"criterion_text":"- 8. Subject and parent(s)/LAR(s) are willing and able to comply with study visits and study procedures.*"}
• {"criterion_text":"- 9. Subject's range is ≥ 4.8 kg (UNIQUE to France)"}

Exclusion criteria

• {"criterion_text":"- 1. Subject is participating in an interventional study designed to treat XLMTM.* * = If a subject is a delayed-treatment control, this inclusion/exclusion criterion must be met before receiving AT132."}
• {"criterion_text":"- 10.Subject has a contraindication to prednisolone.*"}
• {"criterion_text":"- 11.Subject has a contraindication to study drug or ingredients.*"}
• {"criterion_text":"- 12. 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 enrolles under protocol v8 and beyond )."}
• {"criterion_text":"- 13. 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 enrolles under protocol v8 and beyond )."}
• {"criterion_text":"- 14. 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 enrolles under protocol v8 and beyond )."}
• {"criterion_text":"- 15. Subject has a clinically important condition, including CTCAE v4.03 Grade ≥ 2 anemia (< 10 g/dL hemoglobin).*"}
• {"criterion_text":"- 16. Subject has a contraindication to ursodiol (ursodeoxycholic acid).*"}
• {"criterion_text":"- 17. Subject has a prior diagnosis or history of cardiac arrhytmias, myocarditis, or any other cardiac disease (UNIQUE to FRANCE)."}
• {"criterion_text":"- 18. Subject has a contradiction to general anesthesia and to muscle biopsy procedure (UNIQUE to France)."}
• {"criterion_text":"- 2. Subject born < 35 weeks gestation who is still not term as per corrected age."}
• {"criterion_text":"- 3. Subject tests positive for AAV8 neutralizing antibody with titers > 1:20 (subjects under the age of 18 months may be retested in cases where antibodies may have been maternally acquired and titers may decline in the first months of life).*"}
• {"criterion_text":"- 4. 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."}
• {"criterion_text":"- 5. Subject has a clinically important condition or life-threatening disease, other than XLMTM, in the opinion of the Investigator.*"}
• {"criterion_text":"- 6. Subject has a clinically significant underlying liver disease, defined as: • ≥ Grade 3 aspartate aminotransferase (AST) (> 5.0 x upper limit of normal [ULN]; Common Terminology Criteria for Adverse Events [CTCAE] v. 4.03)* • ≥ Grade 3 alanine aminotransferase (ALT) (> 5.0 x ULN; CTCAE v. 4.03)* • Hepatic peliosis or any other clinically significant structural abnormality detected by ultrasound*"}
• {"criterion_text":"- 7. Subject is currently experiencing a clinically important respiratory infection or other active infection.*"}
• {"criterion_text":"- 8.Subject has received pyridostigmine or any medication to treat XLMTM within 3 months before Day 1.*"}
• {"criterion_text":"- 9.Other than as required per protocol, subject has received immunemodulating 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 beenstable for at least 4 weeks before dosing.*"}

Primary endpoints

• {"endpoint_text":"- Primary Efficacy Endpoint: • Change from baseline in hours of ventilation support at Week 24","definition_or_measurement_approach":"Change from baseline in hours of ventilator support measured at Week 24 (change from baseline in hours of ventilation support at Week 24)."}

Secondary endpoints

• {"endpoint_text":"- Key Secondary Efficacy Endpoint: Percentage of subjects achieving functionally independent sitting for at least 30 seconds at Week 24","definition_or_measurement_approach":"Proportion (%) of subjects achieving functionally independent sitting ≥30 seconds evaluated at Week 24."}
• {"endpoint_text":"- Other Secondary Efficacy Endpoints: • Time to reduction in required ventilator support to ≤ 16 hours a day (only in subjects who require invasive ventilation) at Week 24","definition_or_measurement_approach":"Time-to-event measure: time to reduction in ventilator support to ≤16 hours/day, assessed through Week 24 in invasive ventilation subjects."}
• {"endpoint_text":"- • Change from baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) at Week 24","definition_or_measurement_approach":"Change from baseline in CHOP INTEND score measured at Week 24."}
• {"endpoint_text":"- • Change from baseline in maximal inspiratory pressure (MIP) at Week 24","definition_or_measurement_approach":"Change from baseline in maximal inspiratory pressure (MIP) measured at Week 24."}
• {"endpoint_text":"- • Change from baseline in quantitative analysis of myotubularin expression in the muscle biopsy at Week 24","definition_or_measurement_approach":"Change from baseline in quantitative myotubularin expression in muscle biopsy assessed at Week 24."}
• {"endpoint_text":"- • Change from baseline in quality of life assessments at Week 24 (ie, the Assessment of Caregiver Experience with Neuromuscular Disease [ACEND] and Pediatric Quality of Life Inventory [PedsQL])","definition_or_measurement_approach":"Change from baseline in caregiver- and pediatric-reported QoL instruments (ACEND, PedsQL) measured at Week 24."}
• {"endpoint_text":"- • Number (%) of age-appropriate clinically relevant gross motor function milestones attained through Week 24","definition_or_measurement_approach":"Count and percentage of age-appropriate gross motor milestones attained through Week 24."}
• {"endpoint_text":"- • Percentage of subjects achieving full ventilator independence at Week 24","definition_or_measurement_approach":"Proportion (%) of subjects who are fully independent from ventilator at Week 24."}
• {"endpoint_text":"- •Survival","definition_or_measurement_approach":"Survival status through the assessment period (reported as an endpoint)."}
• {"endpoint_text":"- 10 Safety Endpoints: • Adverse events (AEs), serious AEs (SAEs), and findings from safety laboratory tests, 12-lead ECG, echocardiograms (ECHOs), vital signs, growth parameters, physical examinations, liver ultrasounds, antibody formation (anti AAV8, anti MTM1), viral shedding , annualized hospitalization rate , annualized respiratory and non-respiratory SAE rate, and length of stay per hospitalization","definition_or_measurement_approach":"Safety assessed by standard reporting of AEs/SAEs and laboratory/clinical assessments including ECG, ECHO, vitals, growth, exams, liver ultrasound, anti-AAV8/anti-MTM1 antibodies, viral shedding, and hospitalization metrics as listed."}

France

Latest Decision Or Authorization Date

05-02-2025

Number Of Sites

1

Number Of Participants

1

Germany

Latest Decision Or Authorization Date

28-03-2025

Number Of Sites

1

Number Of Participants

4

Primary sponsor

Full Name

Astellas Gene Therapies Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD International Holdings LLC

Responsibilities

sponsorDuties: code 4

Name

Pharmaceutical Product Development LLC

Responsibilities

sponsorDuties: code 4

Name

Fortrea Inc.

Responsibilities

sponsorDuties: code 6

Name

Charles River Laboratories International Inc.

Responsibilities

sponsorDuties: code 4

Name

Q2 Solutions LLC

Responsibilities

sponsorDuties: code 4

Name

Precision For Medicine Inc.

Responsibilities

sponsorDuties: code 4

Name

Bioagilytix Labs LLC

Responsibilities

sponsorDuties: code 4

Third parties

• {"country":"Belgium","full_name":"PPD International Holdings LLC","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Brunel University London","duties_or_roles":"sponsorDuties: code 15 (Respiratory Therapy trainer)","organisation_type":"Educational Institution"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Precision For Medicine Inc.","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q2 Solutions LLC","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Diverge Translational Science Laboratory","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Accellacare Limited","duties_or_roles":"sponsorDuties: code 15 (Home Health)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Rho Inc.","duties_or_roles":"sponsorDuties: code 15 (DMC)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties: code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"Cerba Research","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Charles River Laboratories International Inc.","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"sponsorDuties: code 6","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Mayo Collaborative Services LLC","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"France","full_name":"Genosafe S.A.S.","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q2q Communications Limited","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Franklin Biolabs Inc.","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"sponsorDuties: code 4","organisation_type":"Pharmaceutical company"}