A study to assess the effect of PRO044 in patients with Duchenne muscular dystrophy (Extension study to PRO044-CLIN-01)

• Register: EUCTR
• Last refreshed on: 5 September 2016
• Main ID: EUCTR2013-003605-26-SE
• Date of registration: 26/09/2014
• Prospective Registration: Yes
• Primary sponsor: BioMarin Nederland B.V.
• Public title: A study to assess the effect of PRO044 in patients with Duchenne muscular dystrophy (Extension study to PRO044-CLIN-01)
• Scientific title: A phase II, open label, extension study to assess the effect of PRO044 in patients with Duchenne muscular dystrophy
• Date of first enrolment: 26/11/2014
• Target sample size: 18
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003605-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Netherlands, Sweden

Contacts

• Name: Michael Odontiadis
• Affiliation: BioMarin Nederland B.V.

• Name: Michael Odontiadis
• Affiliation: BioMarin Nederland B.V.

Key inclusion & exclusion 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:
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.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

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

Intervention(s)

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 descriptive name: PS188
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

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.

Timepoint(s) of evaluation of this end point: Week 48

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).

Secondary Outcome(s)

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

Secondary ID(s)

PRO044-CLIN-02

Source(s) of Monetary Support

BioMarin Nederland B.V.