The specific aim of this Phase I/II study is to assess the safety of intravenous administered Morpholino oligomer directed against exon 51 (AVI-4658 PMO).
Primary outcome is safety, tolerability and dose selection for future studies.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
19
AVI-4658 for Injection, is packaged as 100 mg/mL in phosphate buffered saline with 1 mL per vial. Study dosages will be infused over a 1 hour period with Normal saline in 6 dose cohorts.
Great Ormond Street Hospital
London, England, United Kingdom
Royal Victoria Infirmary
Newcastle upon Tyne, England, United Kingdom
Safety and Tolerability
Number of subjects with 1 or more Treatment Emergent Adverse Event that are possibly related to the investigational drug
Time frame: Baseline to 6 months
Treatment Emergent Adverse Events
Number of Patients with Treatment Emergent Adverse Events
Time frame: from Baseline to Follow up (27 weeks)
Pharmacokinetics - Mean Peak Plasma Concentration of AVI-4658 After Administration
Standard Pharmacokinetic parameters estimated using non-compartmental modeling of plasma concentration data.
Time frame: Samples were taken: 30 minutes pre dose; and at 5 (±1), 15 (±2), 30 (±5), 60 (±5), and 90 (±5) minutes; and 2, 4, 6, 8, 12, and 24 hours (all ± 15 minutes) post dose at Weeks 1, 6, and 12
Efficacy of Eteplirsen Over 12 Weeks of Dosing
Efficacy was defined as an estimated change in the percentage of dystrophin positive fibers (assessed by IHC) at Week 14 from Baseline after 12 weekly doses of eterplirsen. This outcome measure represents the number of patients to show an increase in the percentage of dystrophin-positive fibers.
Time frame: Biopsies were taken at Baseline and Week 14
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