Clinical trial NCT01910649: A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess Effect, Safety, Tolerability and PK of Multiple SC Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for IV Dosing as an Alternative Route of Administration
Official title: A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess the Effect, Safety, Tolerability and Pharmacokinetics of Multiple Subcutaneous Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for Intravenous Dosing as an Alternative Route of Administration
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Muscular Dystrophies
Keywords: drisapersen
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2013-07-29
Enrollment: 12
Sex: MALE
Minimum age (years): 5
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the extension phase of this study is to determine whether Drisapersen is effective in the treatment of boys with Duchenne muscular dystrophy resulting from a mutation thought to be corrected by exon 51 skipping.


Eligibility criteria: Inclusion Criteria:

* Boys aged between 5 and 16 years inclusive.
* Duchenne muscular dystrophy resulting from a mutation correctable by treatment with PRO051.
* Not ventilator dependent.
* Life expectancy of at least six months.
* No previous treatment with investigational medicinal treatment within six months prior to the study.
* Willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

* Aberrant RNA splicing and/or aberrant response to PRO051, detected by in vitro PRO051 assay during screening.
* Known presence of dystrophin in 5% of fibers in a pre-study diagnostic muscle biopsy.
* Severe muscle abnormalities defined as increased signal intensity in \>50% of the tibialis anterior muscle at MRI.
* FEV1 and/or FVC \<60% of predicted.
* Current or history of liver or renal disease.
* Acute illness within 4 weeks prior to treatment (Day 1) which may interfere with the measurements.
* Severe mental retardation which in the opinion of the investigator prohibits participation in this study.
* Severe cardiac myopathy which in the opinion of the investigator prohibits participation in this study.
* Need for mechanical ventilation.
* Creatinine concentration above 1.5 times the upper limit of normal (age corrected).
* Serum ASAT and/or ALAT concentration(s) which suggest hepatic impairment.
* Use of anticoagulants, antithrombotics or antiplatelet agents.
* Subject has donated blood less than 90 days before the start of the study.
* Current or history of drug and/or alcohol abuse.
* Participation in another trial with an investigational product.

Primary outcomes:
measure: Acute phase: Safety data
timeFrame: 18 weeks
measure: Acute phase and Continued Treatment Phase : Pharmacokinetics measured by T1/2, Cmax, Ctrough, 7d, tmax, and volume of distribution and clearance
timeFrame: 18 weeks
measure: Acute phase and Continued Treatment Phase : Safety as assessed by the collection of adverse events (AEs)
timeFrame: 72 weeks
measure: Continued Treatment Phase :Safety as assessed by laboratory parameters
timeFrame: 72 weeks
Secondary outcomes:
measure: Acute phase: Production of exon skip 51 messenger Ribonucleic acid (mRNA)
timeFrame: 18 weeks
measure: Acute phase: Presence of dystrophin expression
timeFrame: 18 weeks
measure: Acute phase: Muscle function
timeFrame: 18 weeks
measure: Acute phase: Muscle strength
timeFrame: 18 weeks
measure: Continued Treatment Phase: Exon skip efficiency
timeFrame: 72 weeks
measure: Continued Treatment Phase Dystrophin expression in muscle biopsy
timeFrame: 72 weeks
measure: Continued Treatment Phase: Muscle function
timeFrame: 300 weeks
measure: Continued Treatment Phase: Muscle strength
timeFrame: 300 weeks
Other outcomes:
Locations:
Study officials:
affiliation: UZ Leuven
name: N Goemans, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Goemans NM, Tulinius M, van den Akker JT, Burm BE, Ekhart PF, Heuvelmans N, Holling T, Janson AA, Platenburg GJ, Sipkens JA, Sitsen JM, Aartsma-Rus A, van Ommen GJ, Buyse G, Darin N, Verschuuren JJ, Campion GV, de Kimpe SJ, van Deutekom JC. Systemic administration of PRO051 in Duchenne's muscular dystrophy. N Engl J Med. 2011 Apr 21;364(16):1513-22. doi: 10.1056/NEJMoa1011367. Epub 2011 Mar 23.
citation: Goemans NM, Tulinius M, van den Hauwe M, Kroksmark AK, Buyse G, Wilson RJ, van Deutekom JC, de Kimpe SJ, Lourbakos A, Campion G. Long-Term Efficacy, Safety, and Pharmacokinetics of Drisapersen in Duchenne Muscular Dystrophy: Results from an Open-Label Extension Study. PLoS One. 2016 Sep 2;11(9):e0161955. doi: 10.1371/journal.pone.0161955. eCollection 2016.