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Trial record 11 of 601 for:    Recruiting, Not yet recruiting, Available Studies | "Muscular Diseases"

Gene Transfer Clinical Study in X-Linked Myotubular Myopathy (ASPIRO)

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ClinicalTrials.gov Identifier: NCT03199469
Recruitment Status : Recruiting
First Posted : June 27, 2017
Last Update Posted : October 27, 2017
Sponsor:
Information provided by (Responsible Party):
Audentes Therapeutics

June 21, 2017
June 27, 2017
October 27, 2017
August 2, 2017
March 2019   (Final data collection date for primary outcome measure)
  • Treatment-emergent adverse events (safety and tolerability) [ Time Frame: Baseline through Week 48 ]
    Adverse events, serious adverse events, and laboratory abnormalities (including immunological parameters)
  • Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) [ Time Frame: Baseline to Week 48 ]
    Change in CHOP-INTEND
  • Maximal Inspiratory Pressure (PImax) [ Time Frame: Baseline to Week 48 ]
    Change in PImax
Same as current
Complete list of historical versions of study NCT03199469 on ClinicalTrials.gov Archive Site
  • Motor Function Measure Scale (MFM-20) [ Time Frame: Baseline to Week 48 ]
    Change in MFM-20
  • Bayley III (motor domain) [ Time Frame: Baseline to Week 48 ]
    Change in Bayley III motor domain
  • Muscle Biopsy [ Time Frame: Baseline to Week 48 ]
    Change in quantitative analysis of muscle biopsy
  • Respiratory Endurance (Sprinting) [ Time Frame: Baseline to Week 48 ]
    Change in respiratory endurance
  • Time Off Ventilator [ Time Frame: Baseline to Week 48 ]
    Change in Time Off Ventilator
  • Survival [ Time Frame: Baseline to Week 48 ]
Same as current
  • Quality of Life Assessment: Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) [ Time Frame: Baseline to Week 48 ]
    Change in Quality of Life Assessments
  • Quality of Life Assessment: Pediatric Quality of Life Inventory (PedsQL) - Neuromuscular Module [ Time Frame: Baseline to Week 48 ]
  • Incidence of adverse events, serious adverse events, and laboratory abnormalities (including immunological parameters) [ Time Frame: Baseline to Year 5 ]
Same as current
 
Gene Transfer Clinical Study in X-Linked Myotubular Myopathy
ASPIRO: A Phase 1/2, Randomized, Open-Label, Ascending-Dose, Delayed-Treatment Concurrent Control Clinical Study to Evaluate the Safety and Preliminary Efficacy of AT132, an AAV8-Delivered Gene Therapy in X-Linked Myotubular Myopathy (XLMTM) Patients
This is a Phase 1/2, multinational, open-label, ascending-dose, delayed-treatment concurrent control clinical study to evaluate the safety and preliminary efficacy of AT132 in subjects with X-Linked Myotubular Myopathy aged less than 5 years old. Subjects will receive a single dose of AT132 and will be followed for safety and efficacy for 5 years

This study will evaluate safety and preliminary efficacy of gene transfer in X-Linked Myotubular Myopathy. Subjects will receive a single dose of AT132 delivered intravenously. A maximum of 3 dose levels of AT132 are planned for evaluation in this study. Four subjects will be enrolled at each dose level, including 1 subject at each dose level randomized to control with delayed administration of the investigational medicinal product. Dose escalation to the next dose level will be considered after evaluation of at least 4 weeks of data from all subjects dosed at the current dose level. One of the dose levels will be chosen for dose expansion, and the chosen dose will be administered to all delayed-treatment control subjects.

The primary efficacy endpoint measures will be assessed at Week 48. Subjects will be followed for a total of 5 years after administration of AT132.

This study will utilize an independent Data Monitoring Committee (DMC) that will monitor subject safety and provide recommendations to Audentes regarding dose escalation, dose expansion, and safety matters.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Four subjects will be enrolled at each dose level including 1 subject at each dose level randomized to control with delayed initiation of treatment. One of the dose levels will be chosen for dose expansion and all control subjects will then be treated at the chosen dose level.
Masking: None (Open Label)
Primary Purpose: Treatment
X-Linked Myotubular Myopathy
Genetic: AT132
AT132 is an AAV8 vector containing a functional copy of the human MTM1 (hMTM1) gene.
  • Experimental: Cohort 1
    1.0 x 10^14 vg/kg of AT132 delivered intravenously one time
    Intervention: Genetic: AT132
  • Experimental: Cohort 2
    3.0 x 10^14 vg/kg of AT132 delivered intravenously one time
    Intervention: Genetic: AT132
  • Experimental: Cohort 3
    5.0 x 10^14 vg/kg of AT132 delivered intravenously one time
    Intervention: Genetic: AT132
  • No Intervention: Delayed-Treatment Control
    Delayed-Treatment Control subjects will generally have the same assessments as treated subjects. Once the optimal AT132 dose is selected, delayed-treatment control subjects will undergo pre-treatment baseline procedures to confirm that they remain eligible to receive treatment with AT132. Once eligible, delayed-treatment control subjects are dosed with AT132, they will initiate the same post-dose procedures as subjects who received AT132
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
12
March 2025
March 2019   (Final data collection date for primary outcome measure)

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 Day 1 and/or participated in the ATX-MTM-009 (INCEPTUS) study.
  • Subject requires some mechanical ventilator 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).
  • 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 baseline.

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.
Sexes Eligible for Study: Male
up to 5 Years   (Child)
No
Contact: Kim Trant, Director of Patient Advocacy +1 415 805 1049 trials@audentestx.com
United States
 
 
NCT03199469
ATX-MTM-002
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
Audentes Therapeutics
Audentes Therapeutics
Not Provided
Study Director: Salvador Rico, MD, PhD Audentes Therapeutics
Audentes Therapeutics
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP