First-in-human study of AT132 in X-Linked Myotubular Myopathy (XLMTM) Patients

• Register: EUCTR
• Last refreshed on: 20 July 2020
• Main ID: EUCTR2017-000876-27-FR
• Date of registration: 25/05/2018
• Prospective Registration: No
• Primary sponsor: Audentes Therapeutics Inc.
• Public title: First-in-human study of AT132 in X-Linked Myotubular Myopathy (XLMTM) Patients
• Scientific title: 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 - ASPIRO
• Date of first enrolment: 23/04/2018
• Target sample size: 12
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000876-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Delayed-treatment concurrent control group; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, United Kingdom, United States

Contacts

• Name: Clinical Trials Information
• Affiliation: Audentes Therapeutics Inc.

• Name: Clinical Trials Information
• Affiliation: Audentes Therapeutics Inc.

Key inclusion & exclusion criteria

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's weight is = 4.8 Kg
- 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 12
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

X-linked Myotubular Myopathy (XLMTM)

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: rAAV8-Des-hMTM1
Product Code: AT132
Pharmaceutical Form: Solution for infusion

Primary Outcome(s)

Main Objective: The objectives of the study are as follows:
• To characterize the safety of AT132 in patients with XLMTM in up to 3 ascending dose cohorts.
• To assess the preliminary efficacy of AT132.

Timepoint(s) of evaluation of this end point: Baseline to Week 48

Primary end point(s): - Treatment-emergent adverse events (safety and tolerability)
- Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND)
- Maximal Inspiratory Pressure (PImax)

Secondary Objective: Not applicable

Secondary Outcome(s)

Secondary end point(s): - Motor Function Measure Scale (MFM-20)
- Bayley III (motor domain)
- Muscle Biopsy
- Respiratory Endurance (Sprinting)
- Time Off Ventilator
- Survival

Timepoint(s) of evaluation of this end point: Baseline to Week 48

Secondary ID(s)

NCT03199469

2017-000876-27-GB

ATX-MTM-002

Source(s) of Monetary Support

Audentes Therapeutics Inc.

Ethics review

Status: Approved
Approval date: 19/12/2017
Contact: