Topic: Medicines for Children Research Network
Conditions
Interventions
1. Muscle biopsy: dystrophin production will be determined by comparing results of immunohistological staining and Western blots of muscle homogenates between baseline and after the completion of 12 w
Sponsors
AVI Biopharma, Inc (USA)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Candidates will be included in the study only if all of the following conditions are met: 1. Has provided written informed assent (as required by IRB) and parents/guardians have provided written informed consent 2. Has an out of frame deletion(s) that could be corrected by skipping exon 51 (45 - 50; 47 - 50; 48 - 50; 49 - 50; 50; 52), based on DNA sequencing data 3. Is male and between the ages of greater than or equal to 5 years and less than or equal to 15 years 4. Has a muscle biopsy analysis showing less than 5% revertant fibers present 5. DNA sequencing of exon 51 confirms that no DNA polymorphisms occur that could compromise PMO duplex formation or there is confirmation of in vitro dystrophin production after AVI-4658 exposure to fibroblast or myoblast in vitro cultures 6. Intact right and left bicep muscles or alternative arm muscle group 7. Is able to walk independently 8. Has a forced vital capacity (FVC) greater than or equal to 50% of predicted and does not require night time ventilatory support or supplemental oxygen 9. Receives the standard of care for DMD as recommended by the Muscular Dystrophy Association or the United Kingdom Board of Paediatrics 10. The parent(s) or legal guardian and Subject have undergone counselling about the expectations of this protocol and agree to participate 11. The parent(s) or legal guardian and Subject intend to comply with all study evaluations and return for all study activities
Exclusion criteria
Exclusion criteria: Candidates will be excluded from the study if any of the following conditions are present: 1. A DNA polymorphism within exon 51 that may compromise PMO duplex formation 2. Antibodies to dystrophin 3. Lacks intact right and left bicep muscles or alternative arm muscle group 4. A calculated creatinine clearance less than 70% of predicted normal for age based on the Cockroft and Gault Formula (See the Clinical Study Operations Manual) 5. A left ventricular ejection fraction (LVEF) of less than 35% and/or fractional shortening less than 30% based on echocardiography (ECHO) prior to or during screening 6. A history of respiratory insufficiency as defined by a need for intermittent, night time, or continuous supplemental oxygen 7. A severe cognitive dysfunction rendering the potential Subject unable to understand and comply with the study protocol 8. Any immune deficiency or autoimmune disease 9. A known bleeding disorder or has received chronic anticoagulant treatment within three months of study entry 10. Receipt of pharmacologic treatment, apart from corticosteroids, that might affect muscle strength or function within 8 weeks of study entry (viz., growth hormone, anabolic steroids, and/or creatine protein supplementation) 11. Surgery within 3 months of study entry or planned for anytime during the duration of the study 12. Another clinically significant illness at time of study entry 13. Subject or parent has active psychiatric disorder, has adverse psychosocial circumstances, recent significant emotional loss, and/or history of depressive or anxiety disorder that might interfere with protocol completion or compliance 14. Use of any experimental treatments or has participated in any DMD interventional clinical trial within 4 weeks of study entry
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety of escalating doses of AVI-4658, measured throughout the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pharmacokinetics, measured at 1st, 6th and 12th dosing 2. Efficacy (dystrophin expression) of AVI-4658 at week 14 | — |
Countries
United Kingdom
Outcome results
None listed