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

Primary Purpose

Duchenne Muscular Dystrophy

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

PRO044 SC

PRO044 IV

About this trial

This is an interventional treatment trial for Duchenne Muscular Dystrophy

Eligibility Criteria

5 Years - 16 Years (Child)MaleDoes not accept healthy volunteers

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.

Sites / Locations

UZ Leuven
S.Anna Hospital
Leiden University Medical Center
The Queen Silvia Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Arm Label

PRO044, cohort 1

PRO044, cohort 2

PRO044, cohort 3

PRO044, cohort 4

PRO044, cohort 5

PRO044, cohort 6

PRO044, cohort 7

PRO044, cohort 8

PRO044, cohort 9

Arm Description

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

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

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

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

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

Safety and Tolerability of PRO044

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

Secondary Outcome Measures

PRO044 Pharmacokinetic Cmax (μg/mL) Following Subcutaneous Administration

Pharmacokinetic population evaluated for maximum plasma concentration (Cmax)

Full Information

NCT ID

NCT01037309

First Posted

December 21, 2009

Last Updated

September 19, 2018

Sponsor

BioMarin Pharmaceutical

1. Study Identification

Unique Protocol Identification Number

NCT01037309

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2018

Overall Recruitment Status

Completed

Study Start Date

December 2009 (undefined)

Primary Completion Date

May 2013 (Actual)

Study Completion Date

October 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

BioMarin Pharmaceutical

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Duchenne Muscular Dystrophy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PRO044, cohort 1

Arm Type

Experimental

Arm Description

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

Arm Title

PRO044, cohort 2

Arm Type

Experimental

Arm Description

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

Arm Title

PRO044, cohort 3

Arm Type

Experimental

Arm Description

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

Arm Title

PRO044, cohort 4

Arm Type

Experimental

Arm Description

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

Arm Title

PRO044, cohort 5

Arm Type

Experimental

Arm Description

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

Arm Title

PRO044, cohort 6

Arm Type

Experimental

Arm Description

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

Arm Title

PRO044, cohort 7

Arm Type

Experimental

Arm Description

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

Arm Title

PRO044, cohort 8

Arm Type

Experimental

Arm Description

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

Arm Title

PRO044, cohort 9

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

PRO044 SC

Intervention Description

Subcutaneous injection, once a week, for five weeks

Intervention Type

Drug

Intervention Name(s)

PRO044 IV

Intervention Description

Intravenous injection, once a week, for five weeks

Primary Outcome Measure Information:

Title

Increase in 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

Title

Safety and Tolerability of PRO044

Description

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

Time Frame

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

Secondary Outcome Measure Information:

Title

PRO044 Pharmacokinetic Cmax (μg/mL) Following Subcutaneous Administration

Description

Pharmacokinetic population evaluated for maximum plasma concentration (Cmax)

Time Frame

Week 1, Week 5

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

5 Years

Maximum Age & Unit of Time

16 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

A. Ferlini, PhD

Organizational Affiliation

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

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

J. J. Verschuuren, MD

Organizational Affiliation

Leiden University Medical Center, Leiden, the Netherlands

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

N. Goemans, MD

Organizational Affiliation

UZ Leuven, Leuven, Belgium

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

M. Tulinius, MD

Organizational Affiliation

The Queen Silvia Children's Hospital, Gothenburg, Sweden

Official's Role

Principal Investigator

Facility Information:

Facility Name

UZ Leuven

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

S.Anna Hospital

City

Ferrara

Country

Italy

Facility Name

Leiden University Medical Center

City

Leiden

ZIP/Postal Code

2300

Country

Netherlands

Facility Name

The Queen Silvia Children's Hospital

City

Gothenburg

Country

Sweden

12. IPD Sharing Statement

Learn more about this trial

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

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