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

NCT01910649 | Terminated Phase 2 DMC

• 2 other identifiers: 1146732007-004819-54
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Muscular Dystrophies

Keywords

drisapersen

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• 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

  18 weeks

• Acute phase: Muscle strength

  18 weeks

• Continued Treatment Phase: Exon skip efficiency

  72 weeks

Study Arms (1)

Drisapersen

EXPERIMENTAL

Extension phase of treatment. Intravenous dosing of drisapersen will be investigated as an alternative route of administration

Drug: Drisapersen

Interventions

Drisapersen DRUG

Subcutaneous and Intravenous

Also known as: PRO051

Drisapersen

Eligibility Criteria

• Age: 5 Years - 16 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Related Publications (2)

• 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.

  PMID: 21428760 RESULT

• 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.

  PMID: 27588424 DERIVED

MeSH Terms

Conditions

Muscular Dystrophies

Interventions

PRO051

Condition Hierarchy (Ancestors)

Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• N Goemans, Dr.

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2012
• First Posted: July 29, 2013
• Study Start: March 1, 2008
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: November 7, 2016

Record last verified: 2016-11