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

Muscular Dystrophies Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01910649
• Other study ID #: 114673
• Secondary ID: 2007-004819-54
• Status: Terminated
• Phase: Phase 2
• First received: August 2, 2012
• Last updated: November 4, 2016
• Start date: March 2008
• Est. completion date: September 2016

Study information

• Verified date: November 2016
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Local Medical Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 5 Years to 16 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Drisapersen
Subcutaneous and Intravenous

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

References & Publications (1)

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 admin — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute phase: Safety data	Summarized per dose group	18 weeks	No
Primary	Acute phase and Continued Treatment Phase : Pharmacokinetics measured by T1/2, Cmax, Ctrough, 7d, tmax, and volume of distribution and clearance	Plasma concentration versus time profiles of PRO051 (GSK2402968)	18 weeks	No
Primary	Acute phase and Continued Treatment Phase : Safety as assessed by the collection of adverse events (AEs)	Change from baseline and summarized values	72 weeks	No
Primary	Continued Treatment Phase :Safety as assessed by laboratory parameters	Change from baseline and summarized values	72 weeks	No
Secondary	Acute phase: Production of exon skip 51 messenger Ribonucleic acid (mRNA)		18 weeks	No
Secondary	Acute phase: Presence of dystrophin expression		18 weeks	No
Secondary	Acute phase: Muscle function	Timed tests and 6-minutes walk	18 weeks	No
Secondary	Acute phase: Muscle strength	Quantitative Muscle Testing [QMT]- Cooperative International Neuromuscular Research Group (CINRG) and Manual Muscle Testing [MMT]	18 weeks	No
Secondary	Continued Treatment Phase: Exon skip efficiency		72 weeks	No
Secondary	Continued Treatment Phase Dystrophin expression in muscle biopsy		72 weeks	No
Secondary	Continued Treatment Phase: Muscle function	Timed tests and 6-minutes walk	300 weeks	No
Secondary	Continued Treatment Phase: Muscle strength	Handheld myometry and spirometry	300 weeks	No