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

NCT ID: NCT01037309

Last Updated: 2018-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2013-10-31

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.

Conditions

Duchenne Muscular Dystrophy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PRO044, cohort 1

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

Group Type: EXPERIMENTAL

PRO044 SC

Intervention Type: DRUG

Subcutaneous injection, once a week, for five weeks

PRO044, cohort 2

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

Group Type: EXPERIMENTAL

PRO044 SC

Intervention Type: DRUG

Subcutaneous injection, once a week, for five weeks

PRO044, cohort 3

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

Group Type: EXPERIMENTAL

PRO044 SC

Intervention Type: DRUG

Subcutaneous injection, once a week, for five weeks

PRO044, cohort 4

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

Group Type: EXPERIMENTAL

PRO044 SC

Intervention Type: DRUG

Subcutaneous injection, once a week, for five weeks

PRO044, cohort 5

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

Group Type: EXPERIMENTAL

PRO044 SC

Intervention Type: DRUG

Subcutaneous injection, once a week, for five weeks

PRO044, cohort 6

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

Group Type: EXPERIMENTAL

PRO044 SC

Intervention Type: DRUG

Subcutaneous injection, once a week, for five weeks

PRO044, cohort 7

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

Group Type: EXPERIMENTAL

PRO044 IV

Intervention Type: DRUG

Intravenous injection, once a week, for five weeks

PRO044, cohort 8

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

Group Type: EXPERIMENTAL

PRO044 IV

Intervention Type: DRUG

Intravenous injection, once a week, for five weeks

PRO044, cohort 9

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

Group Type: EXPERIMENTAL

PRO044 IV

Intervention Type: DRUG

Intravenous injection, once a week, for five weeks

Interventions

PRO044 SC

Subcutaneous injection, once a week, for five weeks

Intervention Type: DRUG

PRO044 IV

Intravenous injection, once a week, for five weeks

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

A. Ferlini, PhD

Role: PRINCIPAL_INVESTIGATOR

Università di Ferrara and S.Anna Hospital, Ferrara, Italy

J. J. Verschuuren, MD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center, Leiden, the Netherlands

N. Goemans, MD

Role: PRINCIPAL_INVESTIGATOR

UZ Leuven, Leuven, Belgium

M. Tulinius, MD

Role: PRINCIPAL_INVESTIGATOR

The Queen Silvia Children's Hospital, Gothenburg, Sweden

Locations

UZ Leuven

Leuven, , Belgium

S.Anna Hospital

Ferrara, , Italy

Leiden University Medical Center

Leiden, , Netherlands

The Queen Silvia Children's Hospital

Gothenburg, , Sweden

Countries

Belgium; Italy; Netherlands; Sweden

Other Identifiers

PRO044-CLIN-01

Identifier Type: -

Identifier Source: org_study_id