Open Label, Extension Study of PRO044 in Duchenne Muscular Dystrophy (DMD)
Primary Purpose
Duchenne Muscular Dystrophy
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PRO044 SC 6 mg/kg
PRO044 IV 6 mg/kg
PRO044 IV 9 mg/kg
Sponsored by
About this trial
This is an interventional treatment trial for Duchenne Muscular Dystrophy focused on measuring Duchenne muscular dystrophy, DMD, BioMarin, PRO044
Eligibility Criteria
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.
Sites / Locations
- UZ Leuven
- S.Anna Hospital
- Policlinico Universitario Agostino Gemelli
- Leids Universitair Medisch Centrum
- Drottning Silvias Barn- ochungdomssjukhus
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
PRO044 SC 6 mg/kg
PRO044 IV 6 mg/kg
PRO044 SC 9 mg/kg
Arm Description
Weekly subcutaneous (SC) dosing with 6 mg/kg
Weekly intravenous (IV) dosing with 6 mg/kg
Weekly intravenous (IV) dosing with 9 mg/kg
Outcomes
Primary Outcome Measures
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).
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
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT02329769
First Posted
December 22, 2014
Last Updated
December 6, 2017
Sponsor
BioMarin Pharmaceutical
1. Study Identification
Unique Protocol Identification Number
NCT02329769
Brief Title
Open Label, Extension Study of PRO044 in Duchenne Muscular Dystrophy (DMD)
Official Title
A Phase II, Open Label, Extension Study to Assess the Effect of PRO044 in Patients With Duchenne Muscular Dystrophy
Study Type
Interventional
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Terminated
Study Start Date
December 2014 (Actual)
Primary Completion Date
July 1, 2016 (Actual)
Study Completion Date
August 31, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioMarin Pharmaceutical
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Duchenne Muscular Dystrophy
Keywords
Duchenne muscular dystrophy, DMD, BioMarin, PRO044
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PRO044 SC 6 mg/kg
Arm Type
Experimental
Arm Description
Weekly subcutaneous (SC) dosing with 6 mg/kg
Arm Title
PRO044 IV 6 mg/kg
Arm Type
Experimental
Arm Description
Weekly intravenous (IV) dosing with 6 mg/kg
Arm Title
PRO044 SC 9 mg/kg
Arm Type
Experimental
Arm Description
Weekly intravenous (IV) dosing with 9 mg/kg
Intervention Type
Drug
Intervention Name(s)
PRO044 SC 6 mg/kg
Intervention Type
Drug
Intervention Name(s)
PRO044 IV 6 mg/kg
Intervention Type
Drug
Intervention Name(s)
PRO044 IV 9 mg/kg
Primary Outcome Measure Information:
Title
Efficacy of PRO044 (composite of several measures)
Description
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).
Time Frame
After 48 weeks of treatment
Title
Safety and tolerability of PRO044 (treatement emergent adverse events)
Description
Number of subjects with 1 or more treatement emergent adverse events following SC or IV PRO044 dosing
Time Frame
After 48 weeks of treatment
Secondary Outcome Measure Information:
Title
Assess the pharmacokinetics of PRO044 (composite of several measures)
Description
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.
Time Frame
After 48 weeks of treatment
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
9 Years
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
UZ Leuven
City
Leuven
Country
Belgium
Facility Name
S.Anna Hospital
City
Ferrara
Country
Italy
Facility Name
Policlinico Universitario Agostino Gemelli
City
Roma
Country
Italy
Facility Name
Leids Universitair Medisch Centrum
City
Leiden
Country
Netherlands
Facility Name
Drottning Silvias Barn- ochungdomssjukhus
City
Goteborg
Country
Sweden
12. IPD Sharing Statement
Learn more about this trial
Open Label, Extension Study of PRO044 in Duchenne Muscular Dystrophy (DMD)
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