An Open-Label, Multi-center, Study with a Concurrent Untreated Control Arm to Evaluate the Efficacy and Safety of Eteplirsen in Duchenne Muscular Dystrophy
Study ID: STU 062014-073
This is an open-label, multi-center, study to evaluate the efficacy and safety of eteplirsen in patients with genotypically confirmed DMD with exon deletions amenable to exon 51 skipping (treated group), as compared with untreated control arm of DMD patients amenable to exon skipping (untreated group). Patients will be evaluated for inclusion during a Screening/Baseline period of up to 10 weeks (not including time needed for genotyping if the patient has not been previously genotyped). eligible patients for the treated group will receive once weekly iV infusions of 30 mg/kg eteplirsen for 96 weeks., followed by a safety extension (not to exceed 48 weekso, until the product is commercially available or until patients can transition into a separate eteplirsen study. eligible patients in the untreated group will not receive treatment with eteplirsen, but will complete selected study assessments through 96 weeks. For the treated group, eteplirsen will be administered once weekly via an iV infusion. it is recommended that a topical anesthetic cream (e.g., lidocaine 2.5%, prilocaine 2.5% or LMX4 cream) be applied to the infusion site prior to each administration of eteplirsen. an implanted venous access port may be inserted for eteplirsen administration at the discretion of the family and the investigator. Patients should be observed for possible reactions to the infusion for at least 1 hour after each infusion is completed. option for home infusions. after Week 25 visit, the subject may be given the option to have a home infusion nurse come to their house to give their weekly infusions. if the subject is interested in this option, the subject will need to discuss this with their parent(s)/guardian(s) and their study doctor. The study doctor can provide more information about the home infusion option and help the subject and parents/guardians to decide whether or not this is a good option for them. if the subject and the study doctor agree to have the infusions at home, the subject will still need to return to the study site about once every month for study assessments and an infusion. The subject will also be responsible for continuing to communicate with the study doctor about how they are doing. For all patients, efficacy, including the 6MWT, will be assessed at regularly scheduled study visits by a blinded rater. To minimize assessment bias, every effort will be made to keep the clinical evaluators unaware of the treatment arm of the patients, and all biological efficacy endpoint evaluation will be performed by blinded assessors. upon qualification for the study during the Baseline visit, patients in the treated group will undergo a muscle biopsy and will be randomized to a second muscle biopsy schedule at Week 24, Week 48, 72 or 96 in a 1:2:1:1 ratio. Patients in the untreated control group will not undergo muscle biopsy at any time point. Safety will be continuously monitored for all patients throughtout the study through the collection of (aeS), concomitant medications, physiotherapeutic interventions, laboratory tests, electrocardiograms (eCGs), echocardiograms (eCHos), vital signes and physical examinations. Blood samples for assessing plasma drug concentrations will be obtained at select participating sites from at least 24 patients in the treated group. on Week 1 and week 40 , a single blood sample will be taken within 2 hours prior to the start of the administration of the first dose. on Weeks 8, 16, 24, 32, 40, 62 84 and 96 samples will be taken approximately 5 to 10 minutes after the completion of the infusion (the approximate time of post-dosing maximum plasma concentration for eteplirsen). additional samples will be taken on Weeks 8, 24, 40, and 48 approximately 1 to 2 hours after the completion of the infusion. upon completion of this study, patients in the treated group may participate in an extension treatment phase to receive ongoing eteplirsen treatment.
A patient must meet all of the following criteria to be eligible for this study. 1. Be a male with DMD and meet one of the following criteria: * Have an out-of-frame deletion that may be treated by exon 51 skipping (e.g. deletions of exons 45-50, 47-50, 48-50, 49-50, 50, 52, 52-63). These patients will be enrolled into the treated group. * Have an out-of-frame deletion that is not amenable to treatment by exon 51 skipping but is amenable to treatment by skipping other exons, whole exon deletions in which the reading from may be restored by skipping 1 or 2 exons.) These patients will be enrolled into the untreated control group. 2. Be 7 to 16 years of age, inclusive. 3. Have stable pulmonary function (FVC %] of predicted >=50% and not require nocturnal ventilation) that, in the Investigator[Single Quote]s opinion, is unlikely to decompensate over the duration of the study. 4. Have intact right and left bicep muscle s (the preferred biopsy site) or two alternative upper arm muscle groups. 5. Have been on a stable dose of oral corticosteroids for at least 24 weeks prior to Week 1 and the dose is expected to remain constant (except for modifications to accommodate changes in weight) throughout the study. Note: patients may be allowed to take other (non-RNA antisense or non-gene therapy) medication including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blocking agents (ARBs), [BETA] blockers, potassium, and coenzyme Q, provided they have been on a stable dose for 24 weeks prior to Week 1 and the dose is expected to remain constant throughout the study. 6. Achieve a mean distance of two separate assessments on two consecutive means being within 15% of each other, and with the Screening and Baseline 6MWT conducted 3 to 5 weeks apart. Personal assistance or use of any assistive devices for ambulation is not permitted during the 6MWT. 7. Male patients who are in the treated group and are post-pubertal and sexually active must agree to use, for the entire duration of the study and for 90 days post last dose, a male condom and the female sexual partner must also use a medically acceptable form of birth control (e.g. oral contraceptives). 8. Have a parent(s) or legal guardian(s) who is able to understand and comply with all the study requirements. 9. Be willing to provide informed assent (if applicable) and have a parent(s) or legal guardian(s) who is willing to provide written informed consent for the patient to participate in the study.
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Susan Theresa Iannaccone