Trial Outcomes & Findings for Efficacy Study of AVI-4658 to Induce Dystrophin Expression in Selected Duchenne Muscular Dystrophy Patients (NCT NCT01396239)
NCT ID: NCT01396239
Last Updated: 2020-03-30
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
12 participants
Primary outcome timeframe
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.
Results posted on
2020-03-30
Participant Flow
Participant milestones
| Measure |
AVI-4658 (Eteplirsen) 50 mg/kg
50 mg/kg eteplirsen for 24 weeks
|
Placebo - Week 12 Biopsy
Placebo for 24 Weeks with muscle Biopsy at Week 12
|
AVI-4658 (Eteplirsen) 30 mg/kg
30 mg/kg eteplirsen for 24 weeks
|
Placebo - Week 24 Biopsy
Placebo for 24 weeks with muscle biopsy at Week 24
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
2
|
4
|
2
|
|
Overall Study
COMPLETED
|
4
|
2
|
4
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy Study of AVI-4658 to Induce Dystrophin Expression in Selected Duchenne Muscular Dystrophy Patients
Baseline characteristics by cohort
| Measure |
AVI-4658 (Eteplirsen) 30 mg/kg
n=4 Participants
30 mg/kg eteplirsen for 24 weeks
|
AVI-4658 (Eteplirsen) 50 mg/kg
n=4 Participants
50 mg/kg eteplirsen for 24 weeks
|
Placebo
n=4 Participants
Placebo: phosphate buffered saline solution identical in appearance to eteplirsen for 24 weeks
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Continuous
|
9.3 years
STANDARD_DEVIATION 0.50 • n=5 Participants
|
8.5 years
STANDARD_DEVIATION 1.29 • n=7 Participants
|
8.5 years
STANDARD_DEVIATION 1.73 • n=5 Participants
|
8.8 years
STANDARD_DEVIATION 1.22 • n=4 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
4 participants
n=7 Participants
|
4 participants
n=5 Participants
|
12 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 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.Population: The sample size for the study was selected based on Proof of Principal approach.
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).
Outcome measures
| Measure |
AVI-4658 (Eteplirsen) 30 mg/kg
n=4 Participants
30 mg/kg eteplirsen - Biopsied after 24 weeks of dosing
|
Placebo - Week 24 Biopsy
n=2 Participants
Placebo: Biopsied after 24 weeks of dosing
|
AVI-4658 (Eteplirsen) 50 mg/kg
n=4 Participants
50 mg/kg eteplirsen - Biopsied after 12 weeks of dosing
|
Placebo - Week 12 Biopsy
n=2 Participants
Placebo - Biopsied after 12 weeks of dosing
|
|---|---|---|---|---|
|
Change in the Number (%) of Dystrophin Positive Fibers
|
23 percentage of dystrophin Pos. fibers
Interval 15.9 to 29.0
|
-7.48 percentage of dystrophin Pos. fibers
Interval -8.5 to -6.5
|
0.79 percentage of dystrophin Pos. fibers
Interval -9.3 to 7.4
|
-0.63 percentage of dystrophin Pos. fibers
Interval -5.8 to 4.5
|
SECONDARY outcome
Timeframe: 24 weeksA 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)
Outcome measures
| Measure |
AVI-4658 (Eteplirsen) 30 mg/kg
n=4 Participants
30 mg/kg eteplirsen - Biopsied after 24 weeks of dosing
|
Placebo - Week 24 Biopsy
n=4 Participants
Placebo: Biopsied after 24 weeks of dosing
|
AVI-4658 (Eteplirsen) 50 mg/kg
n=4 Participants
50 mg/kg eteplirsen - Biopsied after 12 weeks of dosing
|
Placebo - Week 12 Biopsy
Placebo - Biopsied after 12 weeks of dosing
|
|---|---|---|---|---|
|
Change From Baseline: 6 Minute Walk Test (6MWT) - Intent to Treat Population (ITT)
|
-134.8 Meters
Standard Error 72.36
|
-2.3 Meters
Standard Error 14.95
|
-17.3 Meters
Standard Error 14.03
|
—
|
SECONDARY outcome
Timeframe: 24 weeksPopulation: 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.
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).
Outcome measures
| Measure |
AVI-4658 (Eteplirsen) 30 mg/kg
n=2 Participants
30 mg/kg eteplirsen - Biopsied after 24 weeks of dosing
|
Placebo - Week 24 Biopsy
n=4 Participants
Placebo: Biopsied after 24 weeks of dosing
|
AVI-4658 (Eteplirsen) 50 mg/kg
n=4 Participants
50 mg/kg eteplirsen - Biopsied after 12 weeks of dosing
|
Placebo - Week 12 Biopsy
Placebo - Biopsied after 12 weeks of dosing
|
|---|---|---|---|---|
|
Change From Baseline: 6 Minute Walk Test (6MWT) - Modified Intent to Treat Population (mITT)
|
-12.5 Meters
Standard Error 1.50
|
-2.3 Meters
Standard Error 14.95
|
-17.3 Meters
Standard Error 14.03
|
—
|
POST_HOC outcome
Timeframe: 24 WeeksAdverse events that occurred in \>30% of the overall patient population across treatment arms.
Outcome measures
| Measure |
AVI-4658 (Eteplirsen) 30 mg/kg
n=4 Participants
30 mg/kg eteplirsen - Biopsied after 24 weeks of dosing
|
Placebo - Week 24 Biopsy
n=4 Participants
Placebo: Biopsied after 24 weeks of dosing
|
AVI-4658 (Eteplirsen) 50 mg/kg
n=4 Participants
50 mg/kg eteplirsen - Biopsied after 12 weeks of dosing
|
Placebo - Week 12 Biopsy
Placebo - Biopsied after 12 weeks of dosing
|
|---|---|---|---|---|
|
Adverse Events >30%
Oropharyngeal Pain
|
3 Number of patients
|
0 Number of patients
|
3 Number of patients
|
—
|
|
Adverse Events >30%
Procedural Pain
|
1 Number of patients
|
3 Number of patients
|
3 Number of patients
|
—
|
|
Adverse Events >30%
Hypokalemia (a known side effect of steroids)
|
2 Number of patients
|
2 Number of patients
|
2 Number of patients
|
—
|
|
Adverse Events >30%
Cough
|
1 Number of patients
|
1 Number of patients
|
2 Number of patients
|
—
|
|
Adverse Events >30%
Extremity Pain
|
0 Number of patients
|
1 Number of patients
|
3 Number of patients
|
—
|
POST_HOC outcome
Timeframe: 24 WeeksFrequency of AEs that the study physician considered to be any of the following: Related; Possibly related; or Probably related to eteplirsen.
Outcome measures
| Measure |
AVI-4658 (Eteplirsen) 30 mg/kg
n=4 Participants
30 mg/kg eteplirsen - Biopsied after 24 weeks of dosing
|
Placebo - Week 24 Biopsy
n=4 Participants
Placebo: Biopsied after 24 weeks of dosing
|
AVI-4658 (Eteplirsen) 50 mg/kg
n=4 Participants
50 mg/kg eteplirsen - Biopsied after 12 weeks of dosing
|
Placebo - Week 12 Biopsy
Placebo - Biopsied after 12 weeks of dosing
|
|---|---|---|---|---|
|
Frequency of AEs Related to Eteplirsen
Intermittent Nausea (mild)
|
0 Number of patients
|
0 Number of patients
|
1 Number of patients
|
—
|
|
Frequency of AEs Related to Eteplirsen
Other AEs related to eteplirsen
|
0 Number of patients
|
0 Number of patients
|
0 Number of patients
|
—
|
Adverse Events
AVI-4658 (Eteplirsen) - 30mg/kg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
AVI-4658 (Eteplirsen) - 50mg/kg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
AVI-4658 (Eteplirsen) - 30mg/kg
n=4 participants at risk
30 mg/kg eteplirsen for 24 weeks
|
AVI-4658 (Eteplirsen) - 50mg/kg
n=4 participants at risk
50 mg/kg eteplirsen for 24 weeks
|
Placebo
n=4 participants at risk
Placebo for 24 weeks - Phosphate buffered saline solution identical in appearance to eteplirsen
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Procedural pain
|
25.0%
1/4 • 24 weeks
|
75.0%
3/4 • 24 weeks
|
75.0%
3/4 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
50.0%
2/4 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
75.0%
3/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
75.0%
3/4 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.0%
1/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
50.0%
2/4 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
75.0%
3/4 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
50.0%
2/4 • 24 weeks
|
|
Nervous system disorders
Balance Disorder
|
25.0%
1/4 • 24 weeks
|
50.0%
2/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Nervous system disorders
Headache
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
50.0%
2/4 • 24 weeks
|
|
General disorders
Pyrexia
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
50.0%
2/4 • 24 weeks
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
50.0%
2/4 • 24 weeks
|
50.0%
2/4 • 24 weeks
|
50.0%
2/4 • 24 weeks
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
1/4 • 24 weeks
|
50.0%
2/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Vascular disorders
Haematoma
|
25.0%
1/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
|
Injury, poisoning and procedural complications
Incision site pain
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Injury, poisoning and procedural complications
Back injury
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Nervous system disorders
Dizziness
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
|
Nervous system disorders
Somnolence
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
General disorders
Injection Site Pain
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
General disorders
Malaise
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
General disorders
Non-cardiac chest pain
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
General disorders
Pain
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
50.0%
2/4 • 24 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
|
Infections and infestations
Rhinitis
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
|
Infections and infestations
Enterobiasis
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
|
Infections and infestations
Soft tissue infection
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
|
Renal and urinary disorders
Polyuria
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
50.0%
2/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Uticaria thermal
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Cardiac disorders
Tachycardia
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Ear and labyrinth disorders
Motion sickness
|
0.00%
0/4 • 24 weeks
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
|
Injury, poisoning and procedural complications
Joint Injury
|
25.0%
1/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
0.00%
0/4 • 24 weeks
|
Additional Information
Edward M. Kaye MD, Interim CEO, SVP & Chief Medical Officer
Sarepta Therapeutics, Inc.
Phone: +1-888-727-3782
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER