Gene Transfer Clinical Study in X-Linked Myotubular Myopathy (ASPIRO)
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ClinicalTrials.gov Identifier: NCT03199469 |
Recruitment Status :
Active, not recruiting
First Posted : June 27, 2017
Last Update Posted : July 8, 2022
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Condition or disease | Intervention/treatment | Phase |
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X-Linked Myotubular Myopathy | Genetic: AT132 | Phase 1 Phase 2 |
This study will evaluate safety and efficacy of gene transfer in X-Linked Myotubular Myopathy. Subjects will receive a single dose of AT132 delivered intravenously.
ASPIRO is being conducted in two parts. Part 1 is a dose escalation phase that is evaluating the preliminary safety and efficacy of AT132 at doses of 1x10^14 vg/kg and 3x10^14 vg/kg. Part 2 of ASPIRO is a pivotal expansion cohort designed to confirm the safety and efficacy of AT132 at a dose of 3x10^14 vg/kg. The pivotal expansion cohort will enroll eight subjects, consisting of four age-matched pairs (within +/- 6 months of age). One subject from each pair will be randomized to receive a single dose of AT132 at 3x10^14 vg/kg, and the other will serve as a delayed treatment control. Eligible delayed treatment control subjects will be administered AT132 after that individual subject has completed the Week 24 visit as a delayed treatment control.
The primary efficacy endpoint measures will be assessed at Week 24. Subjects will be followed for a total of 10 years after administration of AT132.
This study utilizes an independent Data Monitoring Committee (DMC) that monitors subject safety and provides recommendations to Audentes regarding dose escalation, dose expansion, and safety matters.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 26 participants |
Allocation: | Randomized |
Intervention Model: | Sequential Assignment |
Intervention Model Description: | ASPIRO is being conducted in two parts. Part 1 is a dose escalation phase that is evaluating the preliminary safety and efficacy of AT132 at doses of 1x10^14 vg/kg and 3x10^14 vg/kg. Part 2 of ASPIRO is a pivotal expansion cohort designed to confirm the safety and efficacy of AT132 at a dose of 3x10^14 vg/kg. The pivotal expansion cohort will enroll eight subjects, consisting of four age-matched pairs (within +/- 6 months of age). One subject from each pair will be randomized to receive a single dose of AT132 at 3x10^14 vg/kg, and the other will serve as a delayed treatment control. Eligible delayed treatment control subjects will be administered AT132 after that individual subject has completed the Week 24 visit as a delayed treatment control. |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official 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 |
Actual Study Start Date : | August 2, 2017 |
Estimated Primary Completion Date : | March 2024 |
Estimated Study Completion Date : | October 2030 |

Arm | Intervention/treatment |
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Experimental: Lower Dose
1.0 x 10^14 vg/kg of AT132 defined with the use of 1st generation vg titer assay delivered intravenously one time. 1.3 x10^14 vg/kg of AT132 defined with the use of 2nd generation vg titer assay delivered intravenously one time. |
Genetic: AT132
AT132 is an AAV8 vector containing a functional copy of the human MTM1 (hMTM1) gene. |
Experimental: Higher Dose
3.0 x 10^14 vg/kg of AT132 defined with the use of 1st generation vg titer assay delivered intravenously one time. 3.5 x 10^14 vg/kg of AT132 defined with the use of 2nd generation vg titer assay delivered intravenously one time |
Genetic: AT132
AT132 is an AAV8 vector containing a functional copy of the human MTM1 (hMTM1) gene. |
No Intervention: Delayed-Treatment Control
Delayed-Treatment Control subjects will generally have the same assessments as treated subjects. After the follow up period, eligible delayed-treatment control subjects will be dosed with AT132 and initiate the same post-dose procedures as subjects who received AT132.
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- Treatment-emergent adverse events (safety and tolerability) [ Time Frame: Baseline through Week 24 ]Adverse events, serious adverse events, and laboratory abnormalities (including immunological parameters)
- Change from baseline in hours of ventilation support over time through Week 24 [ Time Frame: Baseline to Week 24 ]Change in hours of ventilation
- 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 Frame: Baseline to Week 24 ]Achieve functionally independent sitting for at least 30 seconds
- 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 [ Time Frame: Baseline to Week 24 ]Reduction in required ventilator support
- Change from baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) by Week 24 [ Time Frame: Baseline to Week 24 ]Change in CHOP-INTEND
- Change from baseline in maximal inspiratory pressure (PImax) by Week 24 [ Time Frame: Baseline to Week 24 ]Change in respiratory endurance
- Change from baseline in quantitative analysis of myotubularin expression in the muscle biopsy at Week 24 [ Time Frame: Baseline to Week 24 ]Change in myotubularin expression

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Ages Eligible for Study: | up to 5 Years (Child) |
Sexes Eligible for Study: | Male |
Accepts Healthy Volunteers: | No |
Key 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.
Key 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 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).

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03199469
United States, California | |
UCLA Medical Center | |
Los Angeles, California, United States, 90095 | |
United States, Illinois | |
Ann & Robert H Lurie Children's Hospital of Chicago | |
Chicago, Illinois, United States, 60611 | |
United States, Maryland | |
National Institute of Neurological Disorders and Stroke/NIH Porter | |
Bethesda, Maryland, United States, 208892 | |
Canada, Ontario | |
Hospital for Sick Children | |
Toronto, Ontario, Canada, M5G0A4 | |
France | |
Hopital Armad Trousseau | |
Paris, France, 75012 | |
Germany | |
Kinderklinik und Kinderpoliklinik im Dr. Von Haunerschen Kinderspital Klinikum der Universitat Munchen | |
München, Germany, 80337 |
Study Director: | Weston Miller, MD | Audentes Therapeutics |
Responsible Party: | Astellas Gene Therapies |
ClinicalTrials.gov Identifier: | NCT03199469 |
Other Study ID Numbers: |
ATX-MTM-002 |
First Posted: | June 27, 2017 Key Record Dates |
Last Update Posted: | July 8, 2022 |
Last Verified: | July 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
AAV8-Delivered Gene Therapy XLMTM Adeno Associated Virus |
Muscular Diseases Myopathies, Structural, Congenital Musculoskeletal Diseases Neuromuscular Diseases Nervous System Diseases |