Condition category
Nervous System Diseases
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr Kanagasabai Ganeshaguru


Contact details

Institute of Child Health
30 Guilford Street
United Kingdom

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Dose-ranging study of AVI-4658 to induce dystrophin expression in selected duchenne muscular dystrophy (DMD) patients : a non-randomised interventional screening treatment trial



Study hypothesis

AVI BioPharma is developing AVI-4658, a phosphorodiamidate morpholino oligomer (PMO), for administration to patients with duchenne muscular dystrophy (DMD). It is believed that treatment with AVI-4658 will increase production of a truncated form of dystrophin, such as seen in patients with Becker muscular dystrophy (BMD), and consequently result in improved muscle function and overall quality of life for patients with DMD.

Ethics approval

Gene Therapy Advisory Committee (GTAC) approved on the 5th December 2008 (ref: GTAC157)

Study design

Non-randomised interventional screening treatment trial

Primary study design


Secondary study design

Non randomised controlled trial

Trial setting

GP practices

Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Topic: Medicines for Children Research Network; Subtopic: All Diagnoses; Disease: All Diseases


1. Muscle biopsy: dystrophin production will be determined by comparing results of immunohistological staining and Western blots of muscle homogenates between baseline and after the completion of 12 weekly doses of AVI-4658 (at week 14)
2. Quantitive Muscle Testing (QMT) (i.e., myometry assessments): obtain isometric strength assessments using a hand held myometer. This assessment entails measure of force of right and left knee extension, right and left knee flexion, right and left elbow flexion

Follow up length: 3 months.

Intervention type



Phase I/II

Drug names


Primary outcome measures

Safety of escalating doses of AVI-4658, measured throughout the trial

Secondary outcome measures

1. Pharmacokinetics, measured at 1st, 6th and 12th dosing
2. Efficacy (dystrophin expression) of AVI-4658 at week 14

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

Candidates will be included in the study only if all of the following conditions are met:
1. Has provided written informed assent (as required by IRB) and parents/guardians have provided written informed consent
2. Has an out of frame deletion(s) that could be corrected by skipping exon 51 (45 - 50; 47 - 50; 48 - 50; 49 - 50; 50; 52), based on DNA sequencing data
3. Is male and between the ages of greater than or equal to 5 years and less than or equal to 15 years
4. Has a muscle biopsy analysis showing less than 5% revertant fibers present
5. DNA sequencing of exon 51 confirms that no DNA polymorphisms occur that could compromise PMO duplex formation or there is confirmation of in vitro dystrophin production after AVI-4658 exposure to fibroblast or myoblast in vitro cultures
6. Intact right and left bicep muscles or alternative arm muscle group
7. Is able to walk independently
8. Has a forced vital capacity (FVC) greater than or equal to 50% of predicted and does not require night time ventilatory support or supplemental oxygen
9. Receives the standard of care for DMD as recommended by the Muscular Dystrophy Association or the United Kingdom Board of Paediatrics
10. The parent(s) or legal guardian and Subject have undergone counselling about the expectations of this protocol and agree to participate
11. The parent(s) or legal guardian and Subject intend to comply with all study evaluations and return for all study activities

Participant type


Age group




Target number of participants

Planned sample size: 18; UK sample size: 18

Participant exclusion criteria

Candidates will be excluded from the study if any of the following conditions are present:
1. A DNA polymorphism within exon 51 that may compromise PMO duplex formation
2. Antibodies to dystrophin
3. Lacks intact right and left bicep muscles or alternative arm muscle group
4. A calculated creatinine clearance less than 70% of predicted normal for age based on the Cockroft and Gault Formula (See the Clinical Study Operations Manual)
5. A left ventricular ejection fraction (LVEF) of less than 35% and/or fractional shortening less than 30% based on echocardiography (ECHO) prior to or during screening
6. A history of respiratory insufficiency as defined by a need for intermittent, night time, or continuous supplemental oxygen
7. A severe cognitive dysfunction rendering the potential Subject unable to understand and comply with the study protocol
8. Any immune deficiency or autoimmune disease
9. A known bleeding disorder or has received chronic anticoagulant treatment within three months of study entry
10. Receipt of pharmacologic treatment, apart from corticosteroids, that might affect muscle strength or function within 8 weeks of study entry (viz., growth hormone, anabolic steroids, and/or creatine protein supplementation)
11. Surgery within 3 months of study entry or planned for anytime during the duration of the study
12. Another clinically significant illness at time of study entry
13. Subject or parent has active psychiatric disorder, has adverse psychosocial circumstances, recent significant emotional loss, and/or history of depressive or anxiety disorder that might interfere with protocol completion or compliance
14. Use of any experimental treatments or has participated in any DMD interventional clinical trial within 4 weeks of study entry

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Institute of Child Health
United Kingdom

Sponsor information


AVI Biopharma, Inc (USA)

Sponsor details

3450 Monte Villa Parkway Suite 101
WA 98021
United States of America

Sponsor type




Funder type

Research organisation

Funder name

MRC Clinical Sciences Centre (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

AVI Biopharma, Inc (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2011 results in

Publication citations

  1. Results

    Cirak S, Arechavala-Gomeza V, Guglieri M, Feng L, Torelli S, Anthony K, Abbs S, Garralda ME, Bourke J, Wells DJ, Dickson G, Wood MJ, Wilton SD, Straub V, Kole R, Shrewsbury SB, Sewry C, Morgan JE, Bushby K, Muntoni F, Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study., Lancet, 2011, 378, 9791, 595-605, doi: 10.1016/S0140-6736(11)60756-3.

Additional files

Editorial Notes