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

BioMarin Pharmaceutical

Status and phase: Completed; Phase 2; Phase 1

Conditions: Duchenne Muscular Dystrophy

Treatments: Drug: PRO044 IV; Drug: PRO044 SC

Study type: Interventional

Funder types: Industry

Identifiers

NCT01037309

PRO044-CLIN-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 patients

Sex: Male

Ages: 5 to 16 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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18 participants in 9 patient groups

PRO044, cohort 1

Experimental group

Description:

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

Treatment:

Drug: PRO044 SC

PRO044, cohort 2

Experimental group

Description:

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

Treatment:

Drug: PRO044 SC

PRO044, cohort 3

Experimental group

Description:

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

Treatment:

Drug: PRO044 SC

PRO044, cohort 4

Experimental group

Description:

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

Treatment:

Drug: PRO044 SC

PRO044, cohort 5

Experimental group

Description:

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

Treatment:

Drug: PRO044 SC

PRO044, cohort 6

Experimental group

Description:

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

Treatment:

Drug: PRO044 SC

PRO044, cohort 7

Experimental group

Description:

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

Treatment:

Drug: PRO044 IV

PRO044, cohort 8

Experimental group

Description:

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

Treatment:

Drug: PRO044 IV

PRO044, cohort 9

Experimental group

Description:

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

Treatment:

Drug: PRO044 IV