X-linked Myotubular Myopathy (XLMTM)
Conditions
Interventions
Product Name: rAAV8-Des-hMTM1
Product Code: AT132
Pharmaceutical Form: Solution for infusion
Sponsors
Audentes Therapeutics Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 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. 2. Subject is male. 3. Subject is aged less than 5 years old at Day 1 and/or participated in the ATX MTM 009 (INCEPTUS) study. 4. 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). 5. Subject requiring invasive mechanical ventilator support is fitted with or willing to be fitted with a cuffed tracheostomy tube for some respiratory assessments. 6. Subject has ventilator maximum positive end-expiratory pressure (PEEP) =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subject is participating in an interventional study designed to treat XLMTM. 2. Subject born 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). 4. Subject had recent surgery ( 5.0 x upper limit of normal [ULN]) [CTCAE v. 4.03] = Grade 3 Alanine aminotransferase (> 5.0 x ULN) [CTCAE v. 4.03] Hepatic peliosis or any other clinically significant structural abnormality detected by ultrasound 7. Subject is currently experiencing a clinically important respiratory infection or other active infection. 8. Subject has received pyridostigmine or any medication to treat XLMTM within 3 months before Day 1. 9. 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. 10. Subject has a contraindication to prednisolone. 11. Subject has a contraindication to study drug or ingredients. 12. Subject has previous scoliosis repair surgery/procedure, or planned/expected scoliosis repair surgery/procedure in the 12 months following Day 1 (Part 2 only). 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 only). 14. Subject is able to sit without assistance for at least 30 seconds at screening, in the opinion of the investigator (Part 2 only). 15. Subject has a clinically important condition, including Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade = 2 anemia (< 10g/dL hemoglobin)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objectives of the study are as follows: • To determine the optimal dose of AT132 based on safety and preliminary efficacy in subjects with XLMTM. • To confirm the safety and efficacy of an optimal dose of AT132 in subjects with XLMTM. ;Secondary Objective: Not applicable; Primary end point(s): ENDPOINTS AND SAFETY ASSESSMENTS: The study consists of 2 parts. Part 1 will establish the optimal dose. Part 2 will confirm the safety and efficacy of the optimal dose in a controlled, randomized dose expansion. Safety Assessments: - 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 Primary Efficacy Endpoints: - Change from baseline in hours of ventilation support over time through Week 24 ;Timepoint(s) of evaluation of this end point: Baseline to Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Percentage of subjects achieving functionally independent sitting for at least 30 seconds by Week 24 as assessed by an independent blinded Physical Therapy Adjudication Panel • Time to reduction in required ventilator support to = 16 hours a day (only in subjects who require invasive ventilation) by Week 24 as assessed by independent blinded Pulmonary Adjudication Panel • Change from baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) by Week 24 • Change from baseline in maximal inspiratory pressure (PImax) by Week 24 • Change from baseline in quantitative analysis of myotubularin expression in the muscle biopsy at Week 24 • 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]) • Number (%) of age-appropriate clinically relevant gross motor function milestones attained through Week 24, as assessed by independent blinded Physical Therapy Adjudication Panel • Percentage of subjects achieving full ventilator independence in the absence of acute illness and perioperatively at Week 24, as assessed by independent blinded Pulmonary Adjudication Panel • Change from baseline in the health profiles and overall health status as assessed by the EQ-5D-Y Proxy and the EQ-5D-5L versions at Week 24 • Survival ;Timepoint(s) of evaluation of this end point: Baseline to Week 24 | — |
Countries
France, Germany, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
Audentes Therapeutics Inc.
Outcome results
None listed