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Phase I/II Study of PRO044 in Duchenne Muscular Dystrophy (DMD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01037309
Recruitment Status : Completed
First Posted : December 23, 2009
Results First Posted : April 9, 2015
Last Update Posted : October 16, 2018
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Study Description
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Brief Summary:
The purpose of this study is to see whether PRO044 is safe and effective to use as medication for DMD patients with a mutation around location 44 in the DNA for the dystrophin protein.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Drug: PRO044 SC Drug: PRO044 IV Phase 1 Phase 2

Detailed Description:
To assess the effect of PRO044 at different dose levels in subjects with Duchenne muscular dystrophy To assess the safety and tolerability of PRO044 at different dose levels in subjects with Duchenne muscular dystrophy To determine the pharmacokinetics of PRO044 at different dose levels after subcutaneous and intravenous administration in subjects with Duchenne muscular dystrophy.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/IIa, Open Label, Escalating Dose, Pilot Study to Assess the Effect, Safety, Tolerability and Pharmacokinetics of Multiple Subcutaneous and Intravenous Doses of PRO044 in Patients With Duchenne Muscular Dystrophy
Study Start Date : December 2009
Actual Primary Completion Date : May 2013
Actual Study Completion Date : October 2013

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: PRO044, cohort 1
Subcutaneous injection of 0.5 mg/kg on day 1, 8, 15, 22 and 29.
 Drug: PRO044 SC
Subcutaneous injection, once a week, for five weeks
Experimental: PRO044, cohort 2
Subcutaneous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29.
 Drug: PRO044 SC
Subcutaneous injection, once a week, for five weeks
Experimental: PRO044, cohort 3
Subcutaneous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29.
 Drug: PRO044 SC
Subcutaneous injection, once a week, for five weeks
Experimental: PRO044, cohort 4
Subcutaneous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29.
 Drug: PRO044 SC
Subcutaneous injection, once a week, for five weeks
Experimental: PRO044, cohort 5
Subcutaneous injection of maximally 10 mg/kg on day 1, 8, 15, 22 and 29
 Drug: PRO044 SC
Subcutaneous injection, once a week, for five weeks
Experimental: PRO044, cohort 6
Subcutaneous injection of maximally 12 mg/kg on day 1, 8, 15, 22 and 29
 Drug: PRO044 SC
Subcutaneous injection, once a week, for five weeks
Experimental: PRO044, cohort 7
Intravenous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29
 Drug: PRO044 IV
Intravenous injection, once a week, for five weeks
Experimental: PRO044, cohort 8
Intravenous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29
 Drug: PRO044 IV
Intravenous injection, once a week, for five weeks
Experimental: PRO044, cohort 9
Intravenous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29
 Drug: PRO044 IV
Intravenous injection, once a week, for five weeks


Outcome Measures
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Primary Outcome Measures :
  1. Increase in Dystrophin Expression in the Muscle Biopsies by Immunofluorescence Analyses of Cross-sections and by Western Blot Analyses of Total Protein Extracts [ Time Frame: Within 13 weeks after 5 weeks of treatment ]
  2. Safety and Tolerability of PRO044 [ Time Frame: During the 5 weeks of treatment and during the 13 weeks after treatment ]
    number of subjects with 1 or more treatment emergent adverse events following SC or IV PRO044


Secondary Outcome Measures :
  1. PRO044 Pharmacokinetic Cmax (μg/mL) Following Subcutaneous Administration [ Time Frame: Week 1, Week 5 ]
    Pharmacokinetic population evaluated for maximum plasma concentration (Cmax)


Eligibility Criteria
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Ages Eligible for Study:   5 Years to 16 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Boys aged between 5 and 16 years inclusive.
  2. Duchenne muscular dystrophy resulting from a mutation correctable by treatment with PRO044.
  3. Life expectancy of at least 6 months.
  4. No previous treatment with investigational medicinal treatment within 6 months prior to the start of the (pre)-screening for the study.
  5. No previous treatment with idebenone within 6 months prior to the start of the (pre)-screening for the study.
  6. Willing and able to adhere to the study visit schedule and other protocol requirements.
  7. Written informed consent signed (by parent(s)/legal guardian and/or the patient, according to the local regulations).
  8. Glucocorticosteroids use which is stable for at least 2 months prior first drug administration.

Exclusion Criteria:

  1. Aberrant RNA splicing and/or aberrant response to PRO044, detected by in vitro PRO044 assay during pre-screening.
  2. Known presence of dystrophin in ≥ 5% of fibers in a pre-study diagnostic muscle biopsy.
  3. Severe muscle abnormalities defined as increased signal intensity in >50% of the tibialis anterior muscle at MRI.
  4. FEV1 and/or FVC < 60% of predicted.
  5. Current or history of liver or renal disease.
  6. Acute illness within 4 weeks prior to treatment (Day 1) which may interfere with the measurements.
  7. Severe mental retardation which in the opinion of the investigator prohibits participation in this study.
  8. Severe cardiac myopathy which in the opinion of the investigator prohibits participation in this study.
  9. Need for mechanical ventilation.
  10. Creatinine concentration above 1.5 times the upper limit of normal (age corrected).
  11. Serum ASAT and/or ALAT concentration(s) which suggest hepatic impairment.
  12. Use of anticoagulants, antithrombotics or antiplatelet agents.
  13. Use of idebenone.
  14. Use of any investigational product within 6 months prior to the start of the (pre)-screening for the study.
  15. Subject has donated blood less than 90 days before the start of the (pre)-screening for the study.
  16. Current or history of drug and/or alcohol abuse.
  17. Participation in another trial with an investigational product.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01037309


Locations
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Belgium
UZ Leuven
Leuven, Belgium, 3000
Italy
S.Anna Hospital
Ferrara, Italy
Netherlands
Leiden University Medical Center
Leiden, Netherlands, 2300
Sweden
The Queen Silvia Children's Hospital
Gothenburg, Sweden
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
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Principal Investigator: A. Ferlini, PhD Università di Ferrara and S.Anna Hospital, Ferrara, Italy
Principal Investigator: J. J. Verschuuren, MD Leiden University Medical Center, Leiden, the Netherlands
Principal Investigator: N. Goemans, MD UZ Leuven, Leuven, Belgium
Principal Investigator: M. Tulinius, MD The Queen Silvia Children's Hospital, Gothenburg, Sweden
More Information
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Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT01037309    
Other Study ID Numbers: PRO044-CLIN-01
First Posted: December 23, 2009    Key Record Dates
Results First Posted: April 9, 2015
Last Update Posted: October 16, 2018
Last Verified: September 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
 Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked