Gene Transfer Clinical Study in X-Linked Myotubular Myopathy

Brief Title

Gene Transfer Clinical Study in X-Linked Myotubular Myopathy

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

Brief Summary

      This is a multinational, open-label, ascending-dose, delayed-treatment concurrent control
      clinical study to evaluate the safety and 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
    

Detailed Description

      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 1x1014 vg/kg and 3x1014 vg/kg. Part
      2 of ASPIRO is a pivotal expansion cohort designed to confirm the safety and efficacy of
      AT132 at a dose of 3x1014 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 3x1014 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 5 years after administration of AT132.

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

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Treatment-emergent adverse events (safety and tolerability)

Secondary Outcome

 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

Condition

X-Linked Myotubular Myopathy

Intervention

AT132

Study Arms / Comparison Groups

 Lower Dose
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Genetic

Estimated Enrollment

24

Start Date

August 2, 2017

Completion Date

March 2024

Primary Completion Date

March 2024

Eligibility Criteria

        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).
      

Gender

Male

Ages

N/A - 5 Years

Accepts Healthy Volunteers

No

Contacts

Weston Miller, MD, , 

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT03199469

Organization ID

ATX-MTM-002


Responsible Party

Sponsor

Study Sponsor

Audentes Therapeutics


Study Sponsor

Weston Miller, MD, Study Director, Audentes Therapeutics


Verification Date

May 2021