A Phase 1/2 interventional study of Regimen Selection Phase Group 2 and Regimen Selection Phase Group 3 in Duchenne Muscular Dystrophy, sponsored by BioMarin Pharmaceutical. Terminated at 6 sites in 5 countries. Open to male participants aged 5 Years to 18 Years. Per ClinicalTrials.gov, last updated 2017-12-08.
Sponsored by BioMarin Pharmaceutical · Phase 1/2, Interventional, and Treatment
The purpose of the study is to see whether BMN053 is safe and effective to use as medication for Duchenne muscular dystrophy (DMD) patients with a mutation around location 53 in the DNA for the dystrophin protein.
A Phase I/II, open-label, dose escalating with 48-week treatment study to assess the safety and tolerability, pharmacokinetics, pharmacodynamics and efficacy of BMN 053 (previously known as PRO053) in subjects with Duchenne muscular dystrophy
548 studies on the registry are indexed under Muscular Dystrophies; 89 are open to participants now.
This study's enrollment of 9 is below the median of 24 across 344 interventional studies indexed under Muscular Dystrophies.
Browse Muscular Dystrophies studies →BioMarin Pharmaceutical is the lead sponsor of 110 studies on the registry; 13 are open to participants now.
Of its 17 completed or terminated interventional studies of FDA-regulated products, 12 (71%) have results posted.
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Exclusion Criteria:
In the dose-escalation phase, following screening assessment, two cohorts of three subjects each receive two single doses of BMN 053 in two study periods (i.e., four single doses in total per subject). In each study period they will receive BMN 053 by IV infusion and by SC injection (separated by one week). The proposed doses are 1 mg/kg (Cohort 1, study period 1), 3 mg/kg (Cohort 2, study period 1), 6 mg/kg (Cohort 1, study period 2) and 9 mg/kg (Cohort 2, study period 2). The actual doses may be amended or repeated based on emerging data from previous doses.
Drug: Regimen Selection Phase Group 1 (COMPLETED)
After completion of the dose-escalation period of Cohort 1, the safety data of the subjects will be reviewed by a DSMB and if no safety concerns these subjects will continue to receive 6 mg/kg BMN053 weekly by SC injection for 48 weeks. 3 more treatment-naïve subjects will be entered into this Group. These 6 subjects will form Group 1 of the Regimen Selection phase who received 6 mg/kg SC. At the time of this amendment (4) this part of the study has been completed. Following completion of the dose-escalation study period of Cohort 2 (9 mg/kg), the planned review of the preliminary plasma PK data from the dose-escalation phase showed a relative bioavailability of 50% for BMN053 with SC dosing (50% lower plasma AUC after SC dosing compared to IV dosing). Taking into consideration the risk of injection site reactions noted with similar compounds when administered SC over longer term, the planned 9 mg/kg BMN053 weekly by SC injection will be discontinued to be replaced by an IV regimen.
Drug: Regimen Selection Phase Group 2 · Drug: Regimen Selection Phase Group 3
Thirty additional treatment-naïve subjects will be recruited for the primary evaluation and will receive treatment at the recommended regimen for a total of 48 weeks. Subjects dosed initially in the dose escalation phase and/or the regimen selection phase of the study will not be included in the primary analysis. Following completion of the 2nd study period for Cohort 2, the safety data will be reviewed by the DSMB and in the absence of safety concerns the subjects may enter the 48 week treatment phase and receive 9 mg/kg PRO053 once weekly by SC injection. Three new subjects will enter cohort 2 (i.e. 6 subjects in total at this dose level). After the initial 12 subjects have completed 12 weeks of dosing the dose for the Treatment group (30 new subjects) will be selected based on the totality of the 12-week data from those initial 12 subjects. The initial 12 subjects will also be dosed on the selected dose (i.e. continue on their dose or \[down-\]titrate).
Drug: Treatment Phase Group 4
All subjects who have completed the dose escalation and regimen selection phase of the study (N=15), and subjects who have complete the treatment phase of the study who have tolerated the treatment will be offered to continue dosing in the dosing extension with ongoing assessment of efficacy, safety, and tolerability of BMN 053. Safety, efficacy, PK/PD and biomarker assessments will be performed at scheduled visits; adverse events (AEs) and concomitant medications and therapies will be continuously monitored. The dose extension phase will provide BMN 053 treatment for 48 weeks.
Drug: Dosing Extension
All doses of BMN053 will be administered as IV infusions. The proposed doses are as follows: • 3 mg/kg
All doses of BMN053 will be administered as IV infusions. The proposed doses are as follows: • 4-6 mg/kg
All doses of PRO053 will be administered as IV infusions. The proposed doses will be decided upon completion of the Regimen Selection Phase of Groups 2 and 3
All doses of BMN053 have been administered as subcutaneous injections.
All doses of PRO053 will be administered as IV infusions. The proposed doses will be decided upon completion of the Regimen Selection Phase of Groups 2 and 3 and the Treatment Phase Group 4.
Change from baseline in 6 minute walk test
Time frame: after 48 weeks of treatment phase
Muscle function
Time frame: after 48 weeks treatment phase
Muscle strength
Time frame: after 48 weeks treatment phase
Pulmonary function
Time frame: after 48 weeks treatment phase
Functional outcomes questionnaire
Time frame: after 48 weeks treatment phase
Adverse Events
Time frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase
Safety Laboratory
Time frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase
Cardiac function
Time frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase
Pharmacokinetic parameters at different dose levels
Time frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase
Presence of (BMD-like) dystrophin expression in muscle biopsy
Time frame: after 48 weeks treatment phase
Production of exon skip 53 mRNA in muscle biopsy
Time frame: after 48 weeks treatment phase
This study is terminated, as verified in Dec 2017. You cannot join it, but the record below documents what was studied.
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