Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

Tracking Information
First Submitted Date  ICMJE December 21, 2009
First Posted Date  ICMJE December 23, 2009
Results First Submitted Date  ICMJE September 1, 2014
Results First Posted Date  ICMJE April 9, 2015
Last Update Posted Date October 16, 2018
Study Start Date  ICMJE December 2009
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 19, 2018)
  • 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 ]
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: December 21, 2009)
  • To assess the 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 ]
  • Safety and Tolerability of PRO044 [ Time Frame: During the 5 weeks of treatment and during the 13 weeks after treatment ]
  • Determine the Pharmacokinetics of PRO044 [ Time Frame: During the 5 weeks of treatment and during the 13 weeks after treatment ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2018)
PRO044 Pharmacokinetic Cmax (μg/mL) Following Subcutaneous Administration [ Time Frame: Week 1, Week 5 ]
Pharmacokinetic population evaluated for maximum plasma concentration (Cmax)
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I/II Study of PRO044 in Duchenne Muscular Dystrophy (DMD)
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Duchenne Muscular Dystrophy
Intervention  ICMJE
  • Drug: PRO044 SC
    Subcutaneous injection, once a week, for five weeks
  • Drug: PRO044 IV
    Intravenous injection, once a week, for five weeks
Study Arms  ICMJE
  • Experimental: PRO044, cohort 1
    Subcutaneous injection of 0.5 mg/kg on day 1, 8, 15, 22 and 29.
    Intervention: Drug: PRO044 SC
  • Experimental: PRO044, cohort 2
    Subcutaneous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29.
    Intervention: Drug: PRO044 SC
  • Experimental: PRO044, cohort 3
    Subcutaneous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29.
    Intervention: Drug: PRO044 SC
  • Experimental: PRO044, cohort 4
    Subcutaneous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29.
    Intervention: Drug: PRO044 SC
  • Experimental: PRO044, cohort 5
    Subcutaneous injection of maximally 10 mg/kg on day 1, 8, 15, 22 and 29
    Intervention: Drug: PRO044 SC
  • Experimental: PRO044, cohort 6
    Subcutaneous injection of maximally 12 mg/kg on day 1, 8, 15, 22 and 29
    Intervention: Drug: PRO044 SC
  • Experimental: PRO044, cohort 7
    Intravenous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29
    Intervention: Drug: PRO044 IV
  • Experimental: PRO044, cohort 8
    Intravenous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29
    Intervention: Drug: PRO044 IV
  • Experimental: PRO044, cohort 9
    Intravenous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29
    Intervention: Drug: PRO044 IV
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 14, 2011)
18
Original Estimated Enrollment  ICMJE
 (submitted: December 21, 2009)
12
Actual Study Completion Date  ICMJE October 2013
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 5 Years to 16 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Italy,   Netherlands,   Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01037309
Other Study ID Numbers  ICMJE PRO044-CLIN-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party BioMarin Pharmaceutical
Study Sponsor  ICMJE BioMarin Pharmaceutical
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account BioMarin Pharmaceutical
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP