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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Prosensa Therapeutics
ClinicalTrials.gov Identifier:
NCT01037309
First received: December 21, 2009
Last updated: December 19, 2013
Last verified: December 2013

December 21, 2009
December 19, 2013
December 2009
May 2013   (final data collection date for primary outcome measure)
  • 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 ] [ Designated as safety issue: No ]
  • Safety and tolerability of PRO044 [ Time Frame: During the 5 weeks of treatment and during the 13 weeks after treatment ] [ Designated as safety issue: Yes ]
  • Determine the pharmacokinetics of PRO044 [ Time Frame: During the 5 weeks of treatment and during the 13 weeks after treatment ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01037309 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Phase I/II Study of PRO044 in Duchenne Muscular Dystrophy (DMD)
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

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Duchenne Muscular Dystrophy
  • Drug: PRO044 SC
    Subcutaneous injection, once a week, for five weeks
  • Drug: PRO044 IV
    Intravenous injection, once a week, for five weeks
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
October 2013
May 2013   (final data collection date for primary outcome measure)

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.
Male
5 Years to 16 Years
No
Contact information is only displayed when the study is recruiting subjects
Netherlands,   Italy,   Sweden,   Belgium
 
NCT01037309
PRO044-CLIN-01
Yes
Prosensa Therapeutics
Prosensa Therapeutics
Not Provided
Principal Investigator: A. Ferlini, PhD Università di Ferrara and S.Anna Hospital, Ferrara, Italy
Principal Investigator: J. J.G.M. 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
Prosensa Therapeutics
December 2013

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