Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
AVI-4658 · 3 trials · 2 indications
This study used a modified version of the 6MWT test procedure described in American Thoracic Society (ATS) 2002 guidelines, specifically adapted for patients with Duchenne muscular dystrophy. The participant was asked to walk a set course of 25 meters for 6 minutes (timed) and the distance walked in meters was recorded. Increases from baseline in 6MWT distance are indicative of improvement and decreases from baseline indicate worsening. Baseline here corresponds to the baseline in the parent study (4658-us-201, NCT01396239).
Dystrophin expression as assessed by percent dystrophin positive fibers was measured by immunohistochemistry (IHC) technique using primary anti-dystrophin antibody. Percent change from baseline is the arithmetic difference of the treatment time point minus baseline divided by baseline calculated for individual subjects. Baseline here corresponds to the baseline in the parent study (4658-us-201, NCT01396239).
The primary efficacy endpoint will be based on the pre-treatment and post-treatment change in the number (%) of dystrophin positive fibers as measured in the muscle biopsy tissue on immunohistochemistry (IHC).
Number of subjects with 1 or more Treatment Emergent Adverse Event that are possibly related to the investigational drug
Number of Patients with Treatment Emergent Adverse Events
| Arm | Type | Description |
|---|---|---|
| AVI-4658 (Eteplirsen) | EXPERIMENTAL | Multiple-Dose Extension Study |
| Placebo / Delayed Treatment | PLACEBO_COMPARATOR | 3a. Placebo 50 mg/kg phosphate buffered saline solution identical in appearance to eteplirsen for 24 weeks followed by 50 mg/kg of eteplirsen for 4 weeks. 3b. Placebo 30 mg/kg phosphate buffered saline solution identical in appearance to eteplirsen for 24 weeks followed by 30 mg/kg of eteplirsen for 4 weeks. |
| Cohort 1 - 0.5 mg/kg/wk | EXPERIMENTAL | Subjects in this group will receive a 0.5 mg/kg/wk dose of AVI-4658 over 12 weekly IV infusions in 50 mL of normal saline solution over a 60-minute period |
| Cohort 2 - 1.0 mg/kg/wk | EXPERIMENTAL | Subjects in this group will receive a 1.0 mg/kg/wk dose of AVI-4658 over 12 weekly IV infusions in 50 mL of normal saline solution over a 60-minute period |
| Cohort 3 - 2.0 mg/kg/wk | EXPERIMENTAL | Subjects in this group will receive a 2.0 mg/kg/wk dose of AVI-4658 over 12 weekly IV infusions in 50 mL of normal saline solution over a 60-minute period |
| Cohort 4 - 4.0 mg/kg/wk | EXPERIMENTAL | Subjects in this group will receive a 4.0 mg/kg/wk dose of AVI-4658 over 12 weekly IV infusions in 50 mL of normal saline solution over a 60-minute period |
| Cohort 5 - 10.0 mg/kg/wk | EXPERIMENTAL | Subjects in this group will receive a 10.0 mg/kg/wk dose of AVI-4658 over 12 weekly IV infusions in 50 mL of normal saline solution over a 60-minute period |
| Cohort 6 - 20.0 mg/kg/wk | EXPERIMENTAL | Subjects in this group will receive a 20.0 mg/kg/wk dose of AVI-4658 over 12 weekly IV infusions in 50 mL of normal saline solution over a 60-minute period |
| Name | Type | Description |
|---|---|---|
| AVI-4658 (Eteplirsen) | DRUG | Eteplirsen will be administered once weekly via an IV infusion. There are two treatment groups, 30 mg/kg and 50 mg/kg. |
| Placebo | OTHER | sterile, isotonic, clear, colorless phosphate buffered saline solution of eteplirsen at a concentration of 100 mg/mL in single-use vials containing a nominal volume of 1.0 mL without preservatives. |
| AVI-4658 for Injection | DRUG | 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. |
Inclusion Criteria: A subject must meet all of the following criteria to be eligible for this study. 1. The subject and/or their parent/legal guardian are willing and able to provide signed informed consent. 2. The subject has successfully completed 28 weeks of treatment in Study 4658-US-201. 3. T...
AVI-4658 is an investigational small molecule being developed for the treatment of Duchenne Muscular Dystrophy (DMD), a genetic disorder characterized by progressive muscle degeneration. It is designed to induce dystrophin expression in selected DMD patients. The drug is currently in clinical development and has not been approved by regulatory authorities.
AVI-4658 is being developed by Sarepta Therapeutics, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol SRPT. Sarepta focuses on developing RNA-targeted therapeutics for rare neuromuscular diseases, including Duchenne Muscular Dystrophy.
AVI-4658 is in Phase 2 clinical development for Duchenne Muscular Dystrophy. It has completed two clinical trials, including a Phase 1 dose-ranging study and a Phase 2 efficacy study. The drug remains investigational and has not received FDA approval.
AVI-4658 has completed two clinical trials: NCT00844597, a Phase 1 dose-ranging study in the United Kingdom with 19 participants, and NCT01396239, a Phase 2 efficacy study in the United States with 12 participants. Both trials enrolled male patients with Duchenne Muscular Dystrophy.
AVI-4658 is also known as eteplirsen, as indicated by the clinical trial NCT01540409, which is a rollover study of eteplirsen in subjects with Duchenne Muscular Dystrophy. This trial enrolled 12 participants and was completed in the United States.