Phase I/II Study of PRO044 in Duchenne Muscular Dystrophy (DMD) - Full Text View

Purpose

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	Intervention	Phase
Duchenne Muscular Dystrophy	Drug: PRO044 SC Drug: PRO044 IV	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: Duchenne and Becker muscular dystrophy

MedlinePlus related topics: Muscular Dystrophy

U.S. FDA Resources

Further study details as provided by Prosensa Therapeutics:

Primary Outcome Measures:

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 ]

Estimated Enrollment:	18
Study Start Date:	December 2009
Estimated Study Completion Date:	March 2013
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility

Ages Eligible for Study:	5 Years to 16 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01037309

Locations

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

Prosensa Therapeutics

Investigators

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

More Information

No publications provided

Responsible Party:	Prosensa Therapeutics
ClinicalTrials.gov Identifier:	NCT01037309 History of Changes
Other Study ID Numbers:	PRO044-CLIN-01
Study First Received:	December 21, 2009
Last Updated:	October 10, 2012
Health Authority:	United States: Food and Drug Administration Belgium: Federal Agency for Medicinal Products and Health Products Italy: National Institute of Health Netherlands: Ministry of Health, Welfare and Sport Sweden: Medical Products Agency

Additional relevant MeSH terms:

Muscular Dystrophy, Duchenne
Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases

Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on May 16, 2013