Duchenne muscular dystrophy MedDRA version: 18.1 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: PRO044
Product Code: PRO044
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: PS188 (company code)
CAS Number: 1802402-63-6
Current Sponsor code: PS188
Other desc
Sponsors
BioMarin Nederland B.V.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Subjects previously treated with PRO044 in the PRO044-CLIN-01 study. 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. Are the trial subjects under 18? yes Number of subjects for this age range: 18 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 3 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 anti-coagulants, anti-thrombotics or anti-platelet 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety, tolerability and efficacy of two different doses of intravenous (IV) PRO044 and one dose of subcutaneous (SC) PRO044 in subjects with DMD after 48 weeks treatment. ;Secondary Objective: •To assess the safety, tolerability and efficacy of two different doses of intravenous (IV) PRO044 and one dose of subcutaneous (SC) PRO044 in subjects with DMD over time. •To assess the pharmacokinetic profile of two different dosages and different routes of administration of PRO044 in subjects with DMD. •To assess the pharmacodynamic (PD) effects of two different dosages and different routes of administration of PRO044 in subjects with DMD.;Primary end point(s): Safety Parameters: •Adverse events •Tolerability •Physical examination •Vital signs (temperature, blood pressure, pulse rate, respiration rate) •Laboratory assessments including: -Routine biochemistry and hematology -Urinalysis (routine parameters plus alpha1-microglobulin, microscopy) and 24-hour urine (additionally including protein electrophoresis, urine cystatin C, KIM 1) -Coagulation parameters (aPTT, PT [INR], fibrinogen) -Complement C3 (including split fragments C3a, SC5b and Bb) -Complement C4 and complement Factor H -Pro-inflammatory markers haptoglobulin, MCP 1 -Anti-dystrophin antibodies -Anti-PRO044 antibodies •ECG •Echocardiography •Renal ultrasound. 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). ;Timepoint(s) of evaluation of this end point: Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetic parameters: •t ½ •AUC: 0-24h, 0-8 (where applicable) •Cmax •tmax •CL (for IV subjects) or CL/F (for SC subjects) •PRO044 concentrations in muscle tissue. Pharmacodynamic parameters: •Presence of dystrophin expression after treatment (muscle biopsy) •Nuclear Magnetic Resonance imaging (MRI and MRS) in some subjects in study centers with appropriate imaging capabilities and training. •Exploratory biomarkers (e.g., MMP 9, miRNA 1, miRNA-133).;Timepoint(s) of evaluation of this end point: Week 48 | — |
Countries
Belgium, Netherlands, Sweden
Contacts
Public ContactMichael Odontiadis
BioMarin Nederland B.V.
Outcome results
None listed