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

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

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.

Study Overview

• Status: Terminated
• Conditions: Muscular Dystrophies
• Intervention / Treatment: Drug: Drisapersen

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drisapersen; Extension phase of treatment. Intravenous dosing of drisapersen will be investigated as an alternative route of administration	Drug: Drisapersen; Subcutaneous and Intravenous; Other Names: PRO051

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute phase: Safety data	Summarized per dose group	18 weeks
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
Acute phase and Continued Treatment Phase : Safety as assessed by the collection of adverse events (AEs)	Change from baseline and summarized values	72 weeks
Continued Treatment Phase :Safety as assessed by laboratory parameters	Change from baseline and summarized values	72 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute phase: Production of exon skip 51 messenger Ribonucleic acid (mRNA)		18 weeks
Acute phase: Presence of dystrophin expression		18 weeks
Acute phase: Muscle function	Timed tests and 6-minutes walk	18 weeks
Acute phase: Muscle strength	Quantitative Muscle Testing [QMT]- Cooperative International Neuromuscular Research Group (CINRG) and Manual Muscle Testing [MMT]	18 weeks
Continued Treatment Phase: Exon skip efficiency		72 weeks
Continued Treatment Phase Dystrophin expression in muscle biopsy		72 weeks
Continued Treatment Phase: Muscle function	Timed tests and 6-minutes walk	300 weeks
Continued Treatment Phase: Muscle strength	Handheld myometry and spirometry	300 weeks

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical
• Investigators: Principal Investigator: N Goemans, Dr., UZ Leuven

Publications and helpful links

General Publications

• 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. Erratum In: N Engl J Med. 2011 Oct 6;365(14):1361.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: August 2, 2012
• First Submitted That Met QC Criteria: July 25, 2013
• First Posted (Estimate): July 29, 2013

Study Record Updates

• Last Update Posted (Estimate): November 6, 2016
• Last Update Submitted That Met QC Criteria: November 4, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: drisapersen
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: 114673; 2007-004819-54 (EudraCT Number)