Dose-Ranging Study of AVI-4658 to Induce Dystrophin Expression in Selected Duchenne Muscular Dystrophy (DMD) Patients

This study has been completed.
Sponsor:
Collaborator:
British Medical Research Council
Information provided by (Responsible Party):
Sarepta Therapeutics
ClinicalTrials.gov Identifier:
NCT00844597
First received: December 24, 2008
Last updated: September 3, 2015
Last verified: September 2015
Results First Received: June 8, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Duchenne Muscular Dystrophy
Intervention: Drug: AVI-4658 for Injection

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Cohort 1 - 0.5 mg/kg/wk Subjects in this group received 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 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 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 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 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 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

Participant Flow:   Overall Study
    Cohort 1 - 0.5 mg/kg/wk     Cohort 2 - 1.0 mg/kg/wk     Cohort 3 - 2.0 mg/kg/wk     Cohort 4 - 4.0 mg/kg/wk     Cohort 5 - 10.0 mg/kg/wk     Cohort 6 - 20.0 mg/kg/wk  
STARTED     4     2     2     3     4     4  
COMPLETED     4     2     2     2     4     4  
NOT COMPLETED     0     0     0     1     0     0  
Adverse Event                 0                 0                 0                 1                 0                 0  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Cohort 1 - 0.5mg/kg/wk Subjects in this group received 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 - 1.0mg/kg/wk Subjects in this group received 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 - 2.0mg/kg/wk Subjects in this group received 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 - 4.0mg/kg/wk Subjects in this group received 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 - 10.0mg/kg/wk Subjects in this group received 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 - 20.0mg/kg/wk Subjects in this group received 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
Total Total of all reporting groups

Baseline Measures
    Cohort 1 - 0.5mg/kg/wk     Cohort 2 - 1.0mg/kg/wk     Cohort 3 - 2.0mg/kg/wk     Cohort 4 - 4.0mg/kg/wk     Cohort 5 - 10.0mg/kg/wk     Cohort 6 - 20.0mg/kg/wk     Total  
Number of Participants  
[units: participants]
  4     2     2     3     4     4     19  
Age  
[units: years]
Mean (Standard Deviation)
  8.3  (0.50)     6.0  (0.0)     11.0  (2.83)     9.7  (0.58)     8.8  (2.75)     8.8  (1.26)     8.7  (1.91)  
Gender  
[units: participants]
             
Female     0     0     0     0     0     0     0  
Male     4     2     2     3     4     4     19  
Ethnicity (NIH/OMB)  
[units: participants]
             
Hispanic or Latino     0     0     0     0     0     0     0  
Not Hispanic or Latino     4     2     2     3     4     4     19  
Unknown or Not Reported     0     0     0     0     0     0     0  
Race (NIH/OMB)  
[units: participants]
             
American Indian or Alaska Native     0     0     0     0     0     0     0  
Asian     0     1     0     0     0     0     1  
Native Hawaiian or Other Pacific Islander     0     0     0     0     0     0     0  
Black or African American     0     0     0     0     0     0     0  
White     4     1     2     3     4     4     18  
More than one race     0     0     0     0     0     0     0  
Unknown or Not Reported     0     0     0     0     0     0     0  
Body Weight  
[units: kilograms]
Mean (Standard Deviation)
  33  (4.09)     23.7  (3.46)     42.6  (6.36)     40.1  (19.00)     34.6  (14.01)     33.0  (8.71)     34.5  (10.84)  
Height  
[units: centimeters]
Mean (Standard Deviation)
  127.3  (5.05)     110.7  (4.45)     126.9  (5.09)     126.9  (14.40)     123.7  (10.04)     126.5  (7.18)     124.5  (8.99)  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Safety and Tolerability   [ Time Frame: Baseline to 6 months ]

2.  Primary:   Treatment Emergent Adverse Events   [ Time Frame: from Baseline to Follow up (27 weeks) ]

3.  Secondary:   Pharmacokinetics - Mean Peak Plasma Concentration of AVI-4658 After Administration   [ 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 ]

4.  Secondary:   Efficacy of Eteplirsen Over 12 Weeks of Dosing   [ Time Frame: Biopsies were taken at Baseline and Week 14 ]

5.  Post-Hoc:   Adverse Events >15%   [ Time Frame: 27 Weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Due to the small number of study participants, a single adverse event (AE) in 1 patient exceeds the reporting threshold of 5%. Refer to the "Post-Hoc Outcome Measures" #5 for a summary of frequent and related AEs.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Edward M. Kaye, MD, Interim CEO, SVP & Chief Medical Officer
Organization: Sarepta Therapeutics
phone: 617-274-4003
e-mail: EKaye@Sarepta.com


Publications of Results:

Responsible Party: Sarepta Therapeutics
ClinicalTrials.gov Identifier: NCT00844597     History of Changes
Other Study ID Numbers: AVI-4658-28
Study First Received: December 24, 2008
Results First Received: June 8, 2015
Last Updated: September 3, 2015
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency