Duchenne Muscular Dystrophy MedDRA version: 20.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Lentiviral Vector Trans-Skip gene modified Autologous Mesoangioblasts
Pharmaceutical Form: Solution for injection
Sponsors
The University of Manchester
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Age between 12 and 16 years at time of study entry, provided that participants matching the eligibility criteria can be identified. Otherwise patients of progressively younger age may be recruited up to a minimum age of 8 years. 2. Non-ambulant at the time of recruitment. 3. Confirmed diagnosis of DMD with documented exon 51 skippable mutations in dystrophin gene. 4. Progression of muscle degeneration = to 50% reduction of muscle mass as determined by quantitative MRI (grade 2: Kinali et al. 2011). 5. Written informed consent of caregivers of DMD patients and patient’s assent. Are the trial subjects under 18? yes Number of subjects for this age range: 5 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test. 2. Presence of immune deficiency, neoplastic or autoimmune disease (based on clinical history). 3. Bleeding disorder. 4. Any known allergies to products likely to be used in the study. 5. Prior or ongoing medical condition (e.g. concomitant illness, psychiatric condition, behavioural disorder, drug abuse), medical history, physical findings, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject, making it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results. 6. Ongoing participation in any other therapeutic clinical trial or treatment with exon skipping oligonucleotides. Use of steroids is considered standard care, as well as concomitant medications (e.g. B blockers, ACEI, ARBs, vitamin D, bisphosphonates) and therefore permitted. 7. FS (fraction shortening) 50°). 11. Presence of significant impairment of renal or hepatic function.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: We want to test whether is possible to prepare genetically corrected cells from DMD patients and administer the cells to few muscles of the same patients to verify how much dystrophin is produced. We want to test whether the treatment is safe. ;Secondary Objective: In case of positive results (i.e. dystrophin produced at 10% or more of the level of a healthy muscle) we want to know whether this is sufficient to improve/stabilise the force of contraction of the thumb.; Primary end point(s): We will test safety of treatment and efficacy in restoring synthesis of dystrophin in the injected muscle. Safety: To assess the incidence of adverse events (any grade) in DMD patients treated with intra muscular foot injections of auto-MABS after genetic correction with a lentiviral vector expressing a small nuclear RNA engineered to skip exon 51 of the dystrophin gene. Note: In vitro/in vivo pre-clinical safety assessments will be performed on IMP prior to injection, as described in the IMPD. Efficacy: To determine cell engraftment and dystrophin expression after a single intramuscular injection into the foot medial Extensor Digitorum Brevis (EDB) of genetically corrected auto-MABS. ; Timepoint(s) of evaluation of this end point: Monitoring for SAE will be carried out throughout the trial. Evaluation of dystrophin expression will be carried out three months after IMP injection. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Evaluation will be carried out throughout the trial.; Secondary end point(s): Safety: Incidence and severity of local and systemic adverse events (any grade) in DMD patients treated with intramuscular injections of genetically corrected auto-MABS for one year from the injection. Efficacy: Enhancement, stabilization or decrease of the thumb muscle strength in DMD patients treated with injections of genetically corrected auto-MABS, evaluated periodically (starting at recruitment) up to 1 year from the last injection and in comparison with contralateral non injected thumb. | — |
Countries
United Kingdom
Contacts
Public ContactMohammed Zubair
The University of Manchester
Outcome results
None listed