Duchenne Muscular Dystrophy MedDRA version: 9.1 Level: LLT Classification code 10013801 Term: Duchenne muscular dystrophy
Conditions
Interventions
Product Name: AVI-4658
Product Code: AVI-4658
Pharmaceutical Form: Concentrate for solution for injection
CAS Number: 1173755-55-9
Current Sponsor code: AVI-4658
Concentration unit: mg/ml milligram(s)
Sponsors
AVI BioPharma, Inc.
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 Ethics Committee) 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; 52-63], based on DNA sequencing data. 3. Is male and between the ages of = 5 years and = 15 years. 4. Has a muscle biopsy analysis showing =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Candidates will be excluded from the study if any one of the following conditions are present: 1. A DNA polymorphism within exon 51 that may compromise PMO duplex formation. 2. Known antibodies to dystrophin. 3. Lacks intact right and left biceps 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. 5. A left ventricular ejection fraction (EF) of < 35% and/or fractional shortening < 25% based on echocardiography (ECHO) during screening. 6. A history of respiratory insufficiency as defined by a need for intermittent or continuous supplemental oxygen. 7. A severe cognitive dysfunction rendering the potential subject unable to understand and comply with the study protocol. 8. Any known 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 and/or anabolic steroids). 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, has participated in any DMD interventional clinical trial within 4 weeks of study entry or participation in the AVI-4658-33 i.m. trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this Phase 1b study is to assess the safety of escalating doses of AVI-4658 when administered by 12 weekly doses in boys with Duchenne muscular dystrophy (DMD).;Secondary Objective: The secondary objectives are to explore, after i.v. administration: 1) the pharmacokinetics (PK) of AVI-4658 in patients, and 2) the efficacy of AVI-4658 over 12 weeks of dosing. ;Primary end point(s): The primary outcome measures are measures of safety and tolerability. Safety will be assessed by a series of physical examinations, safety laboratory tests, pulmonary function tests (notably forced vital capacity [FVC]), ECGs, and echocardiography (notably ejection fraction [EF]) by comparison to baseline status for each subject. Tolerability will be assessed by passive reporting, i.e., from the subject and/or parent or guardian) and elicitation of SAEs and AEs by the study staff. Additional safety evaluations: To rule out an immunological inflammatory response biopsied muscles will be studied for immune cell infiltration. In particular, the presence of cytotoxic T-cells will be assessed. Verification will be performed via examination of serial sections. All subjects will be monitored for anti-dystrophin antibodies. | — |
Countries
United Kingdom
Outcome results
None listed