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Efficacy Study of AVI-4658 to Induce Dystrophin Expression in Selected Duchenne Muscular Dystrophy Patients

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ClinicalTrials.gov Identifier: NCT01396239
Recruitment Status : Completed
First Posted : July 18, 2011
Results First Posted : November 9, 2015
Last Update Posted : August 5, 2019
Sponsor:
Information provided by (Responsible Party):
Sarepta Therapeutics, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Duchenne Muscular Dystrophy
Interventions Drug: AVI-4658 (Eteplirsen)
Other: Placebo
Enrollment 12
Recruitment Details  
Pre-assignment Details  
Arm/Group Title AVI-4658 (Eteplirsen) 50 mg/kg Placebo - Week 12 Biopsy AVI-4658 (Eteplirsen) 30 mg/kg Placebo - Week 24 Biopsy
Hide Arm/Group Description 50 mg/kg eteplirsen for 24 weeks Placebo for 24 Weeks with muscle Biopsy at Week 12 30 mg/kg eteplirsen for 24 weeks Placebo for 24 weeks with muscle biopsy at Week 24
Period Title: Overall Study
Started 4 2 4 2
Completed 4 2 4 2
Not Completed 0 0 0 0
Arm/Group Title AVI-4658 (Eteplirsen) 30 mg/kg AVI-4658 (Eteplirsen) 50 mg/kg Placebo Total
Hide Arm/Group Description 30 mg/kg eteplirsen for 24 weeks 50 mg/kg eteplirsen for 24 weeks Placebo: phosphate buffered saline solution identical in appearance to eteplirsen for 24 weeks Total of all reporting groups
Overall Number of Baseline Participants 4 4 4 12
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 12 participants
<=18 years
4
 100.0%
4
 100.0%
4
 100.0%
12
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 4 participants 4 participants 12 participants
9.3  (0.50) 8.5  (1.29) 8.5  (1.73) 8.8  (1.22)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 12 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
4
 100.0%
4
 100.0%
4
 100.0%
12
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 4 participants 4 participants 4 participants 12 participants
4 4 4 12
1.Primary Outcome
Title Change in the Number (%) of Dystrophin Positive Fibers
Hide Description 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).
Time Frame After 12 weeks for 4 patients who received 50 mg/kg and 2 patients who received placebo. After 24 weeks for 4 patients who received 30 mg/kg and 2 patients who received placebo.
Hide Outcome Measure Data
Hide Analysis Population Description
The sample size for the study was selected based on Proof of Principal approach.
Arm/Group Title AVI-4658 (Eteplirsen) 30 mg/kg Placebo - Week 24 Biopsy AVI-4658 (Eteplirsen) 50 mg/kg Placebo - Week 12 Biopsy
Hide Arm/Group Description:
30 mg/kg eteplirsen - Biopsied after 24 weeks of dosing
Placebo: Biopsied after 24 weeks of dosing
50 mg/kg eteplirsen - Biopsied after 12 weeks of dosing
Placebo - Biopsied after 12 weeks of dosing
Overall Number of Participants Analyzed 4 2 4 2
Least Squares Mean (Full Range)
Unit of Measure: percentage of dystrophin Pos. fibers
23
(15.9 to 29.0)
-7.48
(-8.5 to -6.5)
0.79
(-9.3 to 7.4)
-0.63
(-5.8 to 4.5)
2.Secondary Outcome
Title Change From Baseline: 6 Minute Walk Test (6MWT) - Intent to Treat Population (ITT)
Hide Description A key secondary efficacy endpoint will be based on the pre-treatment and post-treatment Change from baseline: 6 Minute Walk Test (6MWT) - Intent to Treat population (ITT)
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 30 mg/kg Eteplirsen 50 mg/kg Eteplirsen Placebo
Hide Arm/Group Description:
30 mg/kg eteplirsen for 24 weeks
50 mg/kg eteplirsen for 24 weeks
Placebo for 24 weeks
Overall Number of Participants Analyzed 4 4 4
Mean (Standard Error)
Unit of Measure: Meters
-134.8  (72.36) -2.3  (14.95) -17.3  (14.03)
3.Secondary Outcome
Title Change From Baseline: 6 Minute Walk Test (6MWT) - Modified Intent to Treat Population (mITT)
Hide Description A key secondary efficacy endpoint will be based on the pre-treatment and post-treatment of the 6-MWT distance. Change from baseline: 6 Minute Walk Test (6MWT) - modified Intent-to-Treat population (mITT).
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population excludes 2 patients in the 30mg/kg arm who showed rapid disease progression within weeks of enrollment, and were unable to complete assessments that required ambulation at or beyond Week 24.
Arm/Group Title 30mg/kg Eteplirsen 50mg/kg Eteplirsen Placebo
Hide Arm/Group Description:
30mg/kg eteplirsen for 24 weeks
50mg/kg eteplirsen for 24 weeks
Placebo for 24 weeks
Overall Number of Participants Analyzed 2 4 4
Mean (Standard Error)
Unit of Measure: Meters
-12.5  (1.50) -2.3  (14.95) -17.3  (14.03)
4.Post-Hoc Outcome
Title Adverse Events >30%
Hide Description Adverse events that occurred in >30% of the overall patient population across treatment arms.
Time Frame 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AVI-4658 (Eteplirsen) - 30mg/kg AVI-4658 (Eteplirsen) - 50mg/kg Placebo
Hide Arm/Group Description:
30 mg/kg eteplirsen for 24 weeks
50 mg/kg eteplirsen for 24 weeks
Placebo for 24 weeks - Phosphate buffered saline solution identical in appearance to eteplirsen
Overall Number of Participants Analyzed 4 4 4
Measure Type: Number
Unit of Measure: Number of patients
Procedural Pain 1 3 3
Oropharyngeal Pain 3 0 3
Hypokalemia (a known side effect of steroids) 2 2 2
Cough 1 1 2
Extremity Pain 0 1 3
5.Post-Hoc Outcome
Title Frequency of AEs Related to Eteplirsen
Hide Description Frequency of AEs that the study physician considered to be any of the following: Related; Possibly related; or Probably related to eteplirsen.
Time Frame 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AVI-4658 (Eteplirsen) - 30mg/kg AVI-4658 (Eteplirsen) - 50mg/kg Placebo
Hide Arm/Group Description:
30 mg/kg eteplirsen for 24 weeks
50 mg/kg eteplirsen for 24 weeks
Placebo for 24 weeks - Phosphate buffered saline solution identical in appearance to eteplirsen
Overall Number of Participants Analyzed 4 4 4
Measure Type: Number
Unit of Measure: Number of patients
Intermittent Nausea (mild) 0 0 1
Other AEs related to eteplirsen 0 0 0
Time Frame 24 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AVI-4658 (Eteplirsen) - 30mg/kg AVI-4658 (Eteplirsen) - 50mg/kg Placebo
Hide Arm/Group Description 30 mg/kg eteplirsen for 24 weeks 50 mg/kg eteplirsen for 24 weeks Placebo for 24 weeks - Phosphate buffered saline solution identical in appearance to eteplirsen
All-Cause Mortality
AVI-4658 (Eteplirsen) - 30mg/kg AVI-4658 (Eteplirsen) - 50mg/kg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
AVI-4658 (Eteplirsen) - 30mg/kg AVI-4658 (Eteplirsen) - 50mg/kg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/4 (0.00%)   0/4 (0.00%)   0/4 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AVI-4658 (Eteplirsen) - 30mg/kg AVI-4658 (Eteplirsen) - 50mg/kg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/4 (100.00%)   4/4 (100.00%)   4/4 (100.00%) 
Cardiac disorders       
Tachycardia * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Ear and labyrinth disorders       
Motion sickness * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%) 
Gastrointestinal disorders       
Vomiting * 1  1/4 (25.00%)  2/4 (50.00%)  0/4 (0.00%) 
Abdominal pain * 1  0/4 (0.00%)  0/4 (0.00%)  2/4 (50.00%) 
Diarrhea * 1  0/4 (0.00%)  1/4 (25.00%)  1/4 (25.00%) 
Nausea * 1  0/4 (0.00%)  1/4 (25.00%)  1/4 (25.00%) 
General disorders       
Pyrexia * 1  1/4 (25.00%)  0/4 (0.00%)  2/4 (50.00%) 
Injection Site Pain * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%) 
Malaise * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%) 
Non-cardiac chest pain * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Pain * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%) 
Infections and infestations       
Rhinitis * 1  0/4 (0.00%)  1/4 (25.00%)  1/4 (25.00%) 
Enterobiasis * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%) 
Nasopharyngitis * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%) 
Soft tissue infection * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%) 
Injury, poisoning and procedural complications       
Procedural pain * 1  1/4 (25.00%)  3/4 (75.00%)  3/4 (75.00%) 
Fall * 1  1/4 (25.00%)  0/4 (0.00%)  1/4 (25.00%) 
Incision site pain * 1  1/4 (25.00%)  0/4 (0.00%)  1/4 (25.00%) 
Arthropod bite * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%) 
Back injury * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Foot fracture * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%) 
Wound dehiscence * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%) 
Joint Injury * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Metabolism and nutrition disorders       
Hypokalaemia  1  2/4 (50.00%)  2/4 (50.00%)  2/4 (50.00%) 
Musculoskeletal and connective tissue disorders       
Back pain * 1  1/4 (25.00%)  0/4 (0.00%)  2/4 (50.00%) 
Pain in Extremity * 1  0/4 (0.00%)  1/4 (25.00%)  3/4 (75.00%) 
Arthralgia * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%) 
Bone Pain * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Muscle Spasms * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%) 
Musculoskeletal Pain * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Nervous system disorders       
Balance Disorder * 1  1/4 (25.00%)  2/4 (50.00%)  0/4 (0.00%) 
Headache * 1  1/4 (25.00%)  0/4 (0.00%)  2/4 (50.00%) 
Dizziness * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%) 
Somnolence * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Renal and urinary disorders       
Polyuria * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Proteinuria * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%) 
Respiratory, thoracic and mediastinal disorders       
Oropharyngeal pain * 1  3/4 (75.00%)  0/4 (0.00%)  3/4 (75.00%) 
Cough * 1  1/4 (25.00%)  1/4 (25.00%)  2/4 (50.00%) 
Nasal Congestion * 1  1/4 (25.00%)  0/4 (0.00%)  2/4 (50.00%) 
Sinus congestion * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Upper respiratory tract congestion * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Skin and subcutaneous tissue disorders       
Dermatitis contact * 1  2/4 (50.00%)  0/4 (0.00%)  0/4 (0.00%) 
Petechiae * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Uticaria thermal * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%) 
Vascular disorders       
Haematoma * 1  1/4 (25.00%)  1/4 (25.00%)  1/4 (25.00%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.0
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" #4 and #5 for a summary of frequent and related AEs.
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 Non Disclosure Agreement provides that the PI, Dr. Jerry Mendell, cannot disclose any “results of the discussions or evaluation” without our consent, and that the “proprietary information shall not be evaluated by any laboratory or clinical testing or experimentation conducted” without our consent.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Edward M. Kaye MD, Interim CEO, SVP & Chief Medical Officer
Organization: Sarepta Therapeutics, Inc.
Phone: +1-888-727-3782
EMail: clinicaltrials@sarepta.com
Layout table for additonal information
Responsible Party: Sarepta Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01396239     History of Changes
Other Study ID Numbers: 4658-us-201
07-2484 ( Other Identifier: Office of Orphan Drug Development )
First Submitted: July 8, 2011
First Posted: July 18, 2011
Results First Submitted: July 2, 2013
Results First Posted: November 9, 2015
Last Update Posted: August 5, 2019