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

Duchenne Muscular Dystrophy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01037309
• Other study ID #: PRO044-CLIN-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 2009
• Est. completion date: October 2013

Study information

• Verified date: September 2018
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: October 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 5 Years to 16 Years

Eligibility

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.

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• PRO044 SC
Subcutaneous injection, once a week, for five weeks
• PRO044 IV
Intravenous injection, once a week, for five weeks

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven
Italy	S.Anna Hospital	Ferrara
Netherlands	Leiden University Medical Center	Leiden
Sweden	The Queen Silvia Children's Hospital	Gothenburg

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Countries where clinical trial is conducted

Belgium,  Italy,  Netherlands,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	PRO044 Pharmacokinetic Cmax (µg/mL) Following Subcutaneous Administration	Pharmacokinetic population evaluated for maximum plasma concentration (Cmax)	Week 1, Week 5