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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: PRO044 SC 6 mg/kg
* Drug: PRO044 IV 6 mg/kg
* Drug: PRO044 IV 9 mg/kg


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

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRO044 SC 6 mg/kg<br>Weekly subcutaneous (SC) dosing with 6 mg/kg | Drug: PRO044 SC 6 mg/kg<br> <br> |
| Experimental: PRO044 IV 6 mg/kg<br>Weekly intravenous (IV) dosing with 6 mg/kg | Drug: PRO044 IV 6 mg/kg<br> <br> |
| Experimental: PRO044 SC 9 mg/kg<br>Weekly intravenous (IV) dosing with 9 mg/kg | Drug: PRO044 IV 9 mg/kg<br> <br> |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Duchenne muscular dystrophy, DMD, BioMarin, PRO044