Safety and Efficacy Study of Antisense Oligonucleotides in Duchenne Muscular Dystrophy

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00159250
• Date of registration: 08/09/2005
• Prospective Registration: Yes
• Primary sponsor: Imperial College London
• Public title: Safety and Efficacy Study of Antisense Oligonucleotides in Duchenne Muscular Dystrophy
• Scientific title: Restoring Dystrophin Expression in Duchenne Muscular Dystrophy: A Phase I/II Clinical Trial Using AVI-4658
• Date of first enrolment: October 26, 2007
• Target sample size: 7
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00159250
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: Single (Participant).
• Phase: Phase 1/Phase 2

Countries of recruitment

United Kingdom

Contacts

• Name: Kate Bushby, MRCP
• Affiliation: Institute of Human Genetics, University of Newcastle upon Tyne

• Name: Francesco Muntoni, FRCPCH
• Affiliation: Dubowitz neuromuscular Centre, Imperial College, London

• Name: Volker Straub, FRCPCH
• Affiliation: Institute of Human Genetics, University of Newcastle upon Tyne

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Subject is male = 10 years and = 17 years of age at the time of study drug
administration.

2. Subject has clinical diagnosis compatible with Duchenne's Muscular Dystrophy (DMD) and
evidence of mutational and dystrophin defects from muscle biopsy consistent with DMD
(out-of frame deletions, absent dystrophin).Eligible deletions are those that can be
rescued by the skipping of exon 51 [45-50; 47-50; 48-50; 49-50; 50; 52; 52-63].

3. Subject has had a muscle biopsy analysed, showing <5% revertant fibres present. Biopsy
may be collected at the time of DMD diagnosis or as part of protocol screening
procedures.

4. Subject is unable to ambulate or stand independently.

5. Subject has Stage 1 to 3 EDB muscle preservation determined by MRI.

6. Subject has a forced vital capacity = 25% confirmed within 3 months from Day One.

7. Subject has mean oxygen saturation monitoring > 94% in overnight domiciliary overnight
sleep study within 3 months of Day One.

8. Subject has the ability to comply with all study evaluations and return for all study.

9. Subject and parent have psychiatric adjustments, adequately supportive psychosocial
circumstances and a full understanding of study aims process and likely outcomes.

Exclusion Criteria:

1. Subject has had external digitorum brevis (EDB) muscle removed.

2. Subject has Stage 4 EDB muscle preservation determined by MRI.

3. Subject has a left ventricular shortening fraction of < 25% and/or an ejection
fraction of < 35% by echocardiography at visit one or within three months of visit
one.

4. Subject has evidence of nocturnal hypoventilation (mean oxygen saturation at night of
= 94%) confirmed via overnight sleep study at Visit One (as screening procedure) or
within 3 months of Visit One by overnight sleep study.

5. Subject has severe respiratory insufficiency defined by the need for invasive or
non-invasive mechanical ventilation (does not include nocturnal ventilatory support).

6. Subject has severe cognitive dysfunction rendering them unable to understand and
collaborate with study protocol.

7. Subject has immune deficiency or autoimmune disease.

8. Subject has a known bleeding disorder or has received chronic anticoagulant treatment
within three months of study entry.

9. Subject has received pharmacologic treatment, apart from corticosteroids, that might
affect muscle strength or function within 8 weeks of study entry (viz.,anabolic
steroids, creatine protein supplementation, albuterol or other beta agonists).

10. Subject has had surgery within 3 months of study entry or planned for anytime during
study.

11. Subject has active significant illness at time of study entry.

12. Subject has is unable to undergo MRI testing (viz., has metal implants).

13. Subject or parent has active psychiatric disorder, has adverse psychosocial
circumstances, recent significant emotional loss, history of depressive or anxiety
disorders that might interfere with protocol completion or compliance.

14. Subject has any known allergies to products likely to be used in the study
(viz.,antiseptics, anaesthetics).

15. Subject has used any experimental treatments or has participated in any clinical trial
within 4 weeks of study entry.

16. Subject has used intranasal, inhaled or topical steroids for a condition other than
muscular dystrophy within 1 weeks of study entry.



Age minimum: 10 Years
Age maximum: 17 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Duchenne Muscular Dystrophy

Intervention(s)

Drug: AVI-4658 (PMO)

Primary Outcome(s)

Number of Participants With Adverse Events Related to AVI-4568 [Time Frame: Baseline up to Day 120]

Number of Participants With Injection Site Reactions [Time Frame: From the Day of Screening to Day 3]

Number of Subjects With Clinically Significant Change From Baseline in Laboratory Values [Time Frame: From the Day of Screening up to Day 28]

Secondary Outcome(s)

Number of Participants With Induced Skipping of Exon 51 in the Treated Extensor Digitorum Brevis (EDB) Muscle Determined by Reverse Transcription Polymerase Chain Reaction [Time Frame: Day 14 to Day 28]

Number of Participants With Restoration of Dystrophin Protein Expression Measured by Immunocytochemistry [Time Frame: Day 14 to Day 28]

Number of Participants With Restoration of Dystrophin Protein Expression Measured by Western Blot Analysis [Time Frame: Day 14 to Day 28]

Secondary ID(s)

05/MRE12/32

2006-003833-33

AVI-4658-33

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Department of Health, United Kingdom

Sarepta Therapeutics, Inc.

Results

• Results available: Yes
• Date Posted: 05/12/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00159250