Open Label, Extension Study of PRO044 in Duchenne Muscular Dystrophy (DMD)

A Phase II, Open Label, Extension Study to Assess the Effect of PRO044 in Patients With Duchenne Muscular Dystrophy

The purpose of this study is to see whether PRO044 is safe and effective to use as medication for Duchenne Muscular Dystrophy (DMD) patients with a mutation around location 44 in the DNA for the dystrophin protein.

Study Overview

• Status: Terminated
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: PRO044 SC 6 mg/kg; Drug: PRO044 IV 6 mg/kg; Drug: PRO044 IV 9 mg/kg

Detailed Description

A Phase II, open-label, extesion study. Following a Screening period of up to one month, subjects previously treated with PRO044, and eligible for enrolment in PRO044-CLIN-02, will be allocated to one of three groups to receive either 6 mg/kg or 9 mg/kg PRO044 weekly by IV infusion or 6 mg/kg weekly by SC injection for 48 weeks.

Safety and tolerability, pharmacokinetics (PK), pharmacodynamic (PD) and efficacy assessments will be conducted at regular intervals throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
    • UZ Leuven
• Italy
  • Ferrara, Italy
    • S.Anna Hospital
  • Roma, Italy
    • Policlinico Universitario Agostino Gemelli
• Netherlands
  • Leiden, Netherlands
    • Leids Universitair Medisch Centrum
• Sweden
  • Goteborg, Sweden
    • Drottning Silvias Barn- ochungdomssjukhus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Subjects previously treated with PRO044.
2. Continued use of glucocorticoids for a minimum of 60 days prior to study entry with a reasonable expectation that the subject will remain on steroids for the duration of the study. Changes to the dose regimen or cessation of glucocorticoids will be at the discretion of the Principle Investigator (PI) in consultation with the subject/parent and the Medical Monitor. If the subject is not on steroids, involvement in the study needs to be discussed with the medical monitor

Exclusion Criteria:

1. Current, or history of, liver or renal disease.
2. Acute illness within 4 weeks prior to the first dose of PRO044 (Week 1) which may interfere with the measurements.
3. Severe cardiac myopathy which in the opinion of the Investigator prohibits participation in this study
4. Need for daytime mechanical ventilation.
5. Screening aPTT above the upper limit of normal (ULN).
6. Screening platelet count below the lower limit of normal (LLN).
7. Use of anticoagulants, antithrombotics or antiplatelet agents.
8. Use of any investigational product within 6 months prior to the start of Screening for the study.
9. Current or history of drug and/or alcohol abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRO044 SC 6 mg/kg; Weekly subcutaneous (SC) dosing with 6 mg/kg	Drug: PRO044 SC 6 mg/kg
Experimental: PRO044 IV 6 mg/kg; Weekly intravenous (IV) dosing with 6 mg/kg	Drug: PRO044 IV 6 mg/kg
Experimental: PRO044 SC 9 mg/kg; Weekly intravenous (IV) dosing with 9 mg/kg	Drug: PRO044 IV 9 mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of PRO044 (composite of several measures)	Efficacy parameters: Muscle Function; 6 Minute Walk Distance (6MWD); North Star Ambulatory Assessment; Timed tests (10-meter walk/run, rising from floor, stair climb); DMD Functional Outcomes Questionnaire (DMD-FOS) -for ambulant subjects only; Egen Klassification - for non-ambulant subjects. Muscle strength; Pulmonary Function (Spirometry); Handheld myometry. Exploratory: Performance Upper Limb (PUL).; Patient Reported Outcome measure (PROM).	After 48 weeks of treatment
Safety and tolerability of PRO044 (treatement emergent adverse events)	Number of subjects with 1 or more treatement emergent adverse events following SC or IV PRO044 dosing	After 48 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the pharmacokinetics of PRO044 (composite of several measures)	Pharmacokinetic parameters: t ½; AUC: 0-24h, 0-∞ (where applicable); Cmax; tmax; CL (for IV subjects) or CL/F (for SC subjects); PRO044 concentrations in muscle tissue.	After 48 weeks of treatment

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): August 31, 2016

Study Registration Dates

• First Submitted: December 22, 2014
• First Submitted That Met QC Criteria: December 31, 2014
• First Posted (Estimate): January 1, 2015

Study Record Updates

• Last Update Posted (Actual): December 8, 2017
• Last Update Submitted That Met QC Criteria: December 6, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: DMD; Duchenne muscular dystrophy; BioMarin; PRO044
• 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: PRO044-CLIN-02