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

NCT01037309 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: PRO044-CLIN-01
• Study Type: interventional
• Target: 18
• Locations: 4 countries
• Sites: 4

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.

Conditions

Duchenne Muscular Dystrophy

Outcome Measures

Primary Outcomes (2)

• Increase in Dystrophin Expression in the Muscle Biopsies by Immunofluorescence Analyses of Cross-sections and by Western Blot Analyses of Total Protein Extracts

  Within 13 weeks after 5 weeks of treatment

• Safety and Tolerability of PRO044

  number of subjects with 1 or more treatment emergent adverse events following SC or IV PRO044

  During the 5 weeks of treatment and during the 13 weeks after treatment

Secondary Outcomes (1)

• PRO044 Pharmacokinetic Cmax (μg/mL) Following Subcutaneous Administration

  Week 1, Week 5

Study Arms (9)

PRO044, cohort 1

EXPERIMENTAL

Subcutaneous injection of 0.5 mg/kg on day 1, 8, 15, 22 and 29.

Drug: PRO044 SC

PRO044, cohort 2

EXPERIMENTAL

Subcutaneous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29.

Drug: PRO044 SC

PRO044, cohort 3

EXPERIMENTAL

Subcutaneous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29.

Drug: PRO044 SC

PRO044, cohort 4

EXPERIMENTAL

Subcutaneous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29.

Drug: PRO044 SC

PRO044, cohort 5

EXPERIMENTAL

Subcutaneous injection of maximally 10 mg/kg on day 1, 8, 15, 22 and 29

Drug: PRO044 SC

PRO044, cohort 6

EXPERIMENTAL

Subcutaneous injection of maximally 12 mg/kg on day 1, 8, 15, 22 and 29

Drug: PRO044 SC

PRO044, cohort 7

EXPERIMENTAL

Intravenous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29

Drug: PRO044 IV

PRO044, cohort 8

EXPERIMENTAL

Intravenous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29

Drug: PRO044 IV

PRO044, cohort 9

EXPERIMENTAL

Intravenous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29

Drug: PRO044 IV

Interventions

PRO044 SC DRUG

Subcutaneous injection, once a week, for five weeks

PRO044, cohort 1; PRO044, cohort 2; PRO044, cohort 3; PRO044, cohort 4; PRO044, cohort 5; PRO044, cohort 6

PRO044 IV DRUG

Intravenous injection, once a week, for five weeks

PRO044, cohort 7; PRO044, cohort 8; PRO044, cohort 9

Eligibility Criteria

• Age: 5 Years - 16 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (4)

UZ Leuven

Leuven, 3000, Belgium

Location

S.Anna Hospital

Ferrara, Italy

Location

Leiden University Medical Center

Leiden, 2300, Netherlands

Location

The Queen Silvia Children's Hospital

Gothenburg, Sweden

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Fiona Lawrence
• Organization: Prosensa

f.lawrence@prosensa.nl

+31(0)713322100

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2009
• First Posted: December 23, 2009
• Study Start: December 1, 2009
• Primary Completion: May 1, 2013
• Study Completion: October 1, 2013
• Last Updated: October 16, 2018
• Results First Posted: April 9, 2015

Record last verified: 2018-09

Locations

SE (1); BE (1); NL (1); IT (1)