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NCT03199469: ASPIRO

A Study of AT132 in Young Children With X-Linked Myotubular Myopathy (XLMTM)

Active, enrolled Phase 2, PHASE3 Results posted Last updated 8 April 2026
What this trial tests

Phase 2, PHASE3 trial testing Resamirigene bilparvovec in X-Linked Myotubular Myopathy in 27 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline
2 August 2017
Primary endpoint
9 September 2021
31 March 2030

Quick facts

Lead sponsorAstellas Gene Therapies
PhasePhase 2, PHASE3
StatusActive, enrolled
Study typeINTERVENTIONAL
Allocationrandomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment27
Start date2 August 2017
Primary completion9 September 2021
Estimated completion31 March 2030
Sites6 locations across France, Canada, United States, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Astellas Gene Therapies — full company profile →

Who can join

Under 5, male only, with X-Linked Myotubular Myopathy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Hours of Ventilation Support at Week 24 Primary · Baseline, week 24

The hours of ventilation support were based on diary data from participants for whom diary data was collected at baseline and by assessment of time off ventilator questionnaire for all other participants. Weekly scores were the average of ventilation hours needed for at least 5 out of the 7 days leading up to and including the analysis visit day (e.g., Day 168 for Week 24). For cases where the diary or the ventilator assessment indicated the ventilator type = "None", then zero was imputed for the number of hours on ventilator.

GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)-8.92± 9.31
3.5 × 10^14 vg/kg (High Dose)-5.84± 5.45
Percentage of Participants Achieving Functionally Independent Sitting for At Least 30 Seconds by Week 24 Secondary · Week 24

Independence to sit is defined as a participant who sits for at least 30 seconds without assistance from another person or object. Data was determined from the motor milestone electronic case report form (eCRF) or the Bayley Scales of Infant and Toddler Development (BSID) subtest performance criteria number 26, used to determine whether the participant achieves (Yes) or doesn't achieve (No) the milestone. If data was not available then they would be included as "missing".

Achieved
GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)83.3
3.5 × 10^14 vg/kg (High Dose)61.5
Not Achieved
GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)16.7
3.5 × 10^14 vg/kg (High Dose)38.5
Time to Reduction in Required Ventilator Support to ≤ 16 Hours a Day From Dosing to Week 24 Secondary · Baseline up to week 24

The reduced ventilator time was obtained directly from the daily diary or assessment of the time off ventilator questionnaire. The first instance of time reduction reported as ≤ 16 hours per day was considered as an event. Kaplan- Meier estimate was used for analysis.

GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)12.14.1 – 16.1
3.5 × 10^14 vg/kg (High Dose)NA17.1 – NA
Change From Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Total Score at Week 24 Secondary · Baseline, week 24

The CHOP INTEND is an assessment scale that was originally designed to quantify motor abilities in infants aged 1.4 to 37.9 months, with spinal muscular atrophy type I (SMA-I) and has been validated for X-linked myotubular myopathy (XLMTM). The scale contains 16 questions, each of which is scored on a scale of 0 to 4, with 0 being no response/ability to perform the movement and 4 highest abilities to perform the task, per CHOP INTEND item instructions. The score used for analysis is the total sum of all 16 questions, which will range from 0 to 64. Higher score indicates better neuromuscular fu

GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)11.86± 15.12
3.5 × 10^14 vg/kg (High Dose)13.25± 13.35
Change From Baseline in Maximal Inspiratory Pressure (MIP) at Week 24 Secondary · Baseline, week 24

MIP is a quick and non-invasive test to measure strength of inspiratory muscles, primarily diaphragm, and allows for assessment of ventilatory failure, restrictive lung disease and respiratory muscle strength. MIP refers to how much air pressure force an individual creates by inhaling through the mouth as hard as possible.

GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)41.07± 35.03
3.5 × 10^14 vg/kg (High Dose)26.72± 28.35
Change From Baseline in Quantitative Analysis of Myotubularin Expression in the Muscle Biopsy at Week 24 Secondary · Baseline, week 24

Myotubularin is a protein, a highly conserved, dual-specific lipid phosphatase that is involved in the development, maturation, and maintenance of skeletal muscle cells. Myotubularin is encoded by an MTM1 gene. The concentration of the sample was normalized such that the equivalent amount of protein was tested per sample.

GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)923.69± 816.09
3.5 × 10^14 vg/kg (High Dose)2848.40± 2903.83
Change From Baseline in Quality of Life Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) Total Score at Week 24 Secondary · Baseline, week 24

ACEND was developed to measure impact on lives of parents/legally authorized representatives /caregivers caring for children with severe neuromuscular disorders. ACEND has 41 items which reflected 2 domains (physical impact \[feeding/grooming/dressing {6 items}, sitting/play {5 items}, transfers {5 items} and mobility {7 items}\] and general caregiver impact \[time {4 items}, emotion {9 items}, and finance {5 items}\]). Score for each item was based on 6- or 5-point ordinal scale, and scores for each domain and subdomain were scored on 0 - 100 scale. Higher scores reflected caregivers experien

GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)20.12± 18.81
3.5 × 10^14 vg/kg (High Dose)13.82± 12.33
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Assessment Total Score at Week 24 Secondary · Baseline, week 24

PedsQL is a tool designed to measure health-related quality of life in healthy children and adolescents and those with acute and chronic health conditions. PedsQL measures the core dimensions of health as delineated by the World Health Organization, as well as role (school) functioning. This questionnaire has different modules that are administered depending on the age and condition of the child. Each item of the questionnaire is measured on a 5-point likert scale from - 0 (Never) to 4 (Almost always). The module is composed of 25 items comprising 3 dimensions: About My Neuromuscular Disease (

GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)9.39± 15.51
3.5 × 10^14 vg/kg (High Dose)12.06± 19.23
Mean Percent of Age-appropriate Clinically Relevant Gross Motor Function Milestones Attained Through Week 24 Secondary · Baseline, weeks 4, 12, 16 and 24

Motor Developmental Milestones included: head control (holds head erect for at least 15 seconds without support), rolls from back to sides (turns from back to both sides), sits without support (sits alone without support for at least 10 seconds), stands with assistance (supports own weight for at least 2 seconds), crawls (makes forward progress of at least 5 feet by crawling on hands and knees), pulls to stand (raises self to standing position using chair or other convenient object for support), walks with assistance (child walks by making coordinated, alternating stepping movements. May hold

Baseline
GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)0.0
3.5 × 10^14 vg/kg (High Dose)12.50± 15.81
Week 4
GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)30.00± 28.28
3.5 × 10^14 vg/kg (High Dose)23.33± 19.66
Week 12
GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)0.0
3.5 × 10^14 vg/kg (High Dose)26.85± 15.06
Week 16
GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)0.0
3.5 × 10^14 vg/kg (High Dose)25.25± 16.26
Week 24
GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)0.0
3.5 × 10^14 vg/kg (High Dose)26.67± 19.36
Percentage of Participants Achieving Full Ventilator Independence at Week 24 Secondary · Week 24

"Full ventilator independence" is defined as: the date of removal from ventilator field on the "Assessment of Ventilator Parameters" eCRF is not blank or "Is subject on a ventilator" = "No" on the same eCRF.

Achieved
GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)28.6
3.5 × 10^14 vg/kg (High Dose)0
Not Achieved
GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)71.4
3.5 × 10^14 vg/kg (High Dose)100
Duration of Overall Survival Secondary · Baseline up to 5 years

Survival status was assessed at each visit until the participant withdraws consent or completes the study. If the participant missed a visit or withdraws for a reason other than withdrawal of consent or death, the site contacted the parent(s)/legally authorized representatives to ascertain if the participant was alive. For participants who withdrew from the study, the participant was contacted every 6 months for 5 years after administration and to assess for survival. Kaplan- Meier estimate was used for analysis.

GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)NA2.10 – NA
3.5 × 10^14 vg/kg (High Dose)NANA – NA
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Secondary · From first dose to 5 years

An AE is any untoward medical occurrence in a participant administered a study drug not necessarily having a causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign, symptom, or disease temporally associated with the use of medicinal product (MP) whether or not considered related to MP. A TEAE is any AEs, regardless of relationship to study drug, that begins or worsens on or after baseline (dosing) visit date.

GroupValue95% CI
1.3 × 10^14 vg/kg (Low Dose)7
3.5 × 10^14 vg/kg (High Dose)17

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose to 5 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

1.3 x 10^14 vg/kg (Low Dose)
Serious: 5/7 (71%)
Deaths: 1/7
3.5 x 10^14 vg/kg (High Dose)
Serious: 13/17 (76%)
Deaths: 3/17

Serious adverse events (62 terms)

ReactionSystem1.3 x 10^14 vg/kg (Low Dose)3.5 x 10^14 vg/kg (High Do…
AscitesGastrointestinal disorders
PyrexiaGeneral disorders
HyperbilirubinaemiaHepatobiliary disorders
TracheitisInfections and infestations
Viral upper respiratory tract infectionInfections and infestations
Device dislocationProduct Issues
ThrombocytopeniaBlood and lymphatic system disorders
Atrial tachycardiaCardiac disorders
Cardiac arrestCardiac disorders
MyocarditisCardiac disorders
TachycardiaCardiac disorders
Combined immunodeficiencyCongenital, familial and genetic disorders
ColitisGastrointestinal disorders
ConstipationGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
Protein-losing gastroenteropathyGastrointestinal disorders
VomitingGastrointestinal disorders
DeathGeneral disorders
CholestasisHepatobiliary disorders
Hepatic function abnormalHepatobiliary disorders
HepatitisHepatobiliary disorders
Hepatitis cholestaticHepatobiliary disorders
HypertransaminasaemiaHepatobiliary disorders
Liver disorderHepatobiliary disorders
Immune system disorderImmune system disorders
Other adverse events (294 terms — click to expand)

ReactionSystem1.3 x 10^14 vg/kg (Low Dose)3.5 x 10^14 vg/kg (High Do…
PyrexiaGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
ConstipationGastrointestinal disorders
HyperbilirubinaemiaHepatobiliary disorders
Blood creatine phosphokinase increasedInvestigations
Viral upper respiratory tract infectionInfections and infestations
C-reactive protein increasedInvestigations
Troponin T increasedInvestigations
COVID-19Infections and infestations
Otitis mediaInfections and infestations
FallInjury, poisoning and procedural complications
Aspartate aminotransferase increasedInvestigations
DiarrhoeaGastrointestinal disorders
Oedema peripheralGeneral disorders
Respiratory syncytial virus infectionInfections and infestations
Respiratory tract infectionInfections and infestations
Activated partial thromboplastin time prolongedInvestigations
Alanine aminotransferase increasedInvestigations
Blood creatine phosphokinase MB increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
Transaminases increasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
Left ventricular hypertrophyCardiac disorders
NauseaGastrointestinal disorders
CholestasisHepatobiliary disorders
Hepatic function abnormalHepatobiliary disorders
HypertransaminasaemiaHepatobiliary disorders
Bacterial tracheitisInfections and infestations
BronchitisInfections and infestations
Clostridium difficile infectionInfections and infestations
Ear infectionInfections and infestations
Lower respiratory tract infectionInfections and infestations
NasopharyngitisInfections and infestations
PharyngitisInfections and infestations
Scarlet feverInfections and infestations
Skin candidaInfections and infestations
Bile acids increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations

Most-reported serious reactions: Ascites, Pyrexia, Hyperbilirubinaemia, Tracheitis, Viral upper respiratory tract infection, Device dislocation, Thrombocytopenia, Atrial tachycardia.

Data from ClinicalTrials.gov NCT03199469 adverse events section.

Sponsor's own description

X-linked myotubular myopathy (XLMTM) is a rare and serious condition present at birth where the muscles do not work properly. There are currently no therapies for this serious condition. The protein myotubularin is needed for muscle development and movement. A gene called MTM1 tells the body to make myotubularin. XLMTM is caused by changes, or mutations, in the MTM1 gene. Changes in the MTM1 gene causes low levels of myotubularin to be made, so the muscles do not work properly. XLMTM may also affect the liver, and in some cases, this can be dangerous and threaten the patient´s life. Gene therapy is a way of getting a healthy copy of a gene into the body. This allows the body's cells to make a normal protein that may reduce disease symptoms. AT132 is a gene therapy that gets a healthy MTM1 gene into the body to help improve muscle development and function in young children with the disease. AT132 does not treat liver disease, and because of the way the treatment works, it may make liver problems worse. AT132 was the gene therapy treatment given to children who participated in this study and is not available to the public. In this study, AT132 was given to children for the first time. Due to the occurrence of severe complications and fatalities associated with administration of AT132, the study has been stopped and no further participants will be enrolled. The main aim of the study is to check how long young children need machines to support breathing (ventilation support) after AT132. Due to the occurrence of severe complications and fatalities associated with administration of AT132, the study has been stopped and no further participants will be enrolled. This study included children with XLMTM under 5 years old who had breathing problems caused by XLMTM. They couldn't take part if they were born prematurely, recently had surgery, had liver disease or other condition or disease the study doctor thought was medically important. The study did enroll participants with medically significant liver disease. This is an open-label study. This means that young children and their caregivers, and clinic staff know that young children received AT132. This study was designed with 2 parts and is now in a long-term follow-up phase to collect information on the safety and improvements in muscle function in the children who received AT132. In Part 1, small groups of young children were given different doses of AT132, with one group receiving a lower dose and one group receiving a higher dose of AT132. The purpose of giving the two doses was to determine which dose was best for treating the muscle disease. After receiving AT132, a medical panel of experts reviewed each child for safety and for how their muscles responded. AT132 did not demonstrate appropriate safety at either dose. Administration of AT132 was stopped. Children who received AT132 are being monitored for 10 years for safety and to understand how their muscles function over time.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Viral vector platforms within the gene therapy landscape.
    Bulcha JT, Wang Y, Ma H, Tai PWL, et al · · 2021 · cited 899× · PMID 33558455 · DOI 10.1038/s41392-021-00487-6
  2. Severe Toxicity in Nonhuman Primates and Piglets Following High-Dose Intravenous Administration of an Adeno-Associated Virus Vector Expressing Human SMN.
    Hinderer C, Katz N, Buza EL, Dyer C, et al · · 2018 · cited 661× · PMID 29378426 · DOI 10.1089/hum.2018.015
  3. Current Clinical Applications of In Vivo Gene Therapy with AAVs.
    Mendell JR, Al-Zaidy SA, Rodino-Klapac LR, Goodspeed K, et al · · 2021 · cited 544× · PMID 33309881 · DOI 10.1016/j.ymthe.2020.12.007
  4. AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer.
    Costa Verdera H, Kuranda K, Mingozzi F. · · 2020 · cited 493× · PMID 31972133 · DOI 10.1016/j.ymthe.2019.12.010
  5. Directed evolution of a family of AAV capsid variants enabling potent muscle-directed gene delivery across species.
    Tabebordbar M, Lagerborg KA, Stanton A, King EM, et al · · 2021 · cited 401× · PMID 34506722 · DOI 10.1016/j.cell.2021.08.028
  6. Systemic AAV Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy.
    Duan D. · · 2018 · cited 350× · PMID 30093306 · DOI 10.1016/j.ymthe.2018.07.011
  7. Human Immune Responses to Adeno-Associated Virus (AAV) Vectors.
    Ronzitti G, Gross DA, Mingozzi F. · · 2020 · cited 269× · PMID 32362898 · DOI 10.3389/fimmu.2020.00670
  8. Identification of a myotropic AAV by massively parallel in vivo evaluation of barcoded capsid variants.
    Weinmann J, Weis S, Sippel J, Tulalamba W, et al · · 2020 · cited 205× · PMID 33116134 · DOI 10.1038/s41467-020-19230-w

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03199469.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing