Trial record 18 of 52 for:    Open Studies | "Muscular Dystrophy, Duchenne"

A Phase I/II Study of PRO053 in Subjects With Duchenne Muscular Dystrophy (DMD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Prosensa Therapeutics
Sponsor:
Information provided by (Responsible Party):
Prosensa Therapeutics
ClinicalTrials.gov Identifier:
NCT01957059
First received: July 2, 2013
Last updated: October 21, 2013
Last verified: October 2013
  Purpose

The purpose of the study is to see whether PRO053 is safe and effective to use as medication for Duchenne muscular dystrophy (DMD) patients with a mutation around location 53 in the DNA for the dystrophin protein.


Condition Intervention Phase
Duchenne Muscular Dystrophy
Drug: Cohort 1
Drug: Cohort 2
Drug: 48-week treatment phase
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-label, Dose Escalating With 48 Week Treatment Study to Assess the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of PRO053 in Subjects With Duchenne Muscular Dystrophy.

Resource links provided by NLM:


Further study details as provided by Prosensa Therapeutics:

Primary Outcome Measures:
  • Change from baseline in 6 minute walk test [ Time Frame: after 48 weeks of treatment phase ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Muscle function [ Time Frame: after 48 weeks treatment phase ] [ Designated as safety issue: No ]
  • Muscle strength [ Time Frame: after 48 weeks treatment phase ] [ Designated as safety issue: No ]
  • Pulmonary function [ Time Frame: after 48 weeks treatment phase ] [ Designated as safety issue: No ]
  • Functional outcomes questionnaire [ Time Frame: after 48 weeks treatment phase ] [ Designated as safety issue: No ]
  • Adverse Events [ Time Frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase ] [ Designated as safety issue: Yes ]
  • Safety Laboratory [ Time Frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase ] [ Designated as safety issue: Yes ]
  • Cardiac function [ Time Frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic parameters at different dose levels [ Time Frame: after single intravenous and subcutaneous doses, and after 48 weeks of treatment phase ] [ Designated as safety issue: No ]
  • Presence of (BMD-like) dystrophin expression in muscle biopsy [ Time Frame: after 48 weeks treatment phase ] [ Designated as safety issue: No ]
  • Production of exon skip 53 mRNA in muscle biopsy [ Time Frame: after 48 weeks treatment phase ] [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: June 2013
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 & 3
In the dose-escalation phase, following screening assessment, 3 subjects receive 2 single doses of PRO053 in each of 2 study periods (i.e., 4 single doses in total per subject). In each study period they will receive PRO053 by IV infusion and by SC injection (separated by 1 week). The proposed doses are 1 mg/kg (study period 1) and 6 mg/kg (study period 2).
Drug: Cohort 1

All doses of PRO053 will be administered as IV infusions and SC injections. The proposed doses are as follows:

  • 1 mg/kg (Cohort1)
  • 6 mg/kg (Cohort 1)
Experimental: Cohort 2 & 4
In the dose-escalation phase, following screening assessment, 3 subjects receive 2 single doses of PRO053 in each of 2 study periods (i.e., 4 single doses in total per subject). In each study period they will receive PRO053 by IV infusion and by SC injection (separated by 1 week). The proposed doses are 3 mg/kg (study period 1) and 9 mg/kg (study period 2).
Drug: Cohort 2

All doses of PRO053 will be administered as IV infusions and SC injections. The proposed doses are as follows:

  • 3 mg/kg (Cohort 2)
  • 9 mg/kg (Cohort 2)
Experimental: 48-week Treatment Phase

Following completion of the 2nd study period for Cohort 1, the safety data will be reviewed by the DSMB and in the absence of safety concerns the subjects may enter the 48 week treatment phase and receive 6 mg/kg PRO053 once weekly by SC injection. Three new subjects will enter cohort 1 (i.e. 6 subjects in total at this dose level).

Following completion of the 2nd study period for Cohort 2, the safety data will be reviewed by the DSMB and in the absence of safety concerns the subjects may enter the 48 week treatment phase and receive 9 mg/kg PRO053 once weekly by SC injection. Three new subjects will enter cohort 2 (i.e. 6 subjects in total at this dose level).

After the initial 12 subjects have completed 12 weeks of dosing the dose for the Treatment group (30 new subjects) will be selected based on the totality of the 12-week data from those initial 12 subjects. The initial 12 subjects will also be dosed on the selected dose (i.e. continue on their dose or [down-]titrate).

Drug: 48-week treatment phase

All doses of PRO053 will be administered as SC injections. The proposed doses for the first 12 weeks are as follows:

  • 6 mg/kg given once weekly
  • 9 mg/kg given once weekly

Detailed Description:

A Phase I/II, open-label study. The study consists of two phases; a single dose escalation phase and a 48 week treatment phase. All subjects will have a screening period prior to their first dose of PRO053.

Safety and Tolerability, pharmacokinetics (PK), pharmacodynamic (PD) and efficacy assessments will be conducted at regular intervals throughout the study.

  Eligibility

Ages Eligible for Study:   5 Years to 18 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Duchenne muscular dystrophy resulting from a mutation correctable by treatment with PRO053 confirmed by a state-of-the-art DNA diagnostic technique covering all DMD gene exons, including but not limited to MLPA (Multiplex Ligation-dependent Probe Amplification), CGH (Comparative Genomic Hybridisation), SCAIP (Single Condition Amplification/Internal Primer) or HRMCA (High-Resolution Melting Curve Analysis).
  2. Ambulant boys aged at least 5 years on the day of first dosing able to walk for at least 230 metres in the 6 minute walking distance (6MWD) test. In addition, results of the 6MWD test must be within ±30 metres of each other at 2 of 3 pre-treatment visits (screen 1, 2 and baseline) prior to first PRO053 administration.
  3. Adequate quality for biopsy (confirmed with MRI) of the lateral head of the gastrocnemius muscle. Only under exceptional circumstances will an alternative muscle (preferably brachii) be considered for biopsy and only following discussion between the Principal Investigator and the Prosensa Medical Monitor.
  4. Life expectancy of at least 3 years after inclusion in the study.
  5. Glucocorticosteroid use which is stable for at least 3 months prior to first PRO053 administration. Subjects must have been receiving glucocorticosteroids for at least 6 months prior to the first PRO053 administration.
  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 subject, according to the local regulations).
  8. In France, a subject will be eligible for inclusion in this study only if either affiliated to, or a beneficiary of, a social security category.

Exclusion Criteria:

  1. Known presence of ≥5% dystrophin in fibres of a pre-study diagnostic muscle biopsy (i.e. historic muscle biopsy taken prior to written informed consent for this study).
  2. Current or history of liver disease or impairment.
  3. Current or history of renal disease or impairment.
  4. At least two aPTT above upper limit of normal (ULN) within the last month prior to first dose of PRO053.
  5. Screening platelet count below the lower limit of normal (LLN).
  6. Acute illness within 4 weeks prior to first dose of PRO053 which may interfere with the study assessments.
  7. Severe mental retardation and/or behavioural problems which, in the opinion of the Investigator, prohibit participation in this study.
  8. Severe cardiomyopathy which, in the opinion of the Investigator prohibits participation in this study. If a subject has a left ventricular ejection fraction <45% at screening, the Investigator should discuss inclusion of the subject with the Medical Monitor.
  9. Expected need for daytime mechanical ventilation within the next year.
  10. Use of anticoagulants, antithrombotics or antiplatelet agents.
  11. Use of idebenone or other forms of coenzyme Q10 within 1 month prior to the start of the screening for the study.
  12. Use of nutritional or herbal supplements which, in the opinion of the Investigator, may influence muscle performance within 1 month prior to first dose of PRO053.
  13. Use of any other investigational product or participation in another trial with an investigational product, within 6 months prior to the start of the screening for the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01957059

Contacts
Contact: Sarah Hill +44 (0)7899 067 239 s.hill@prosensa.nl
Contact: Sandra Castro +44 (0)7968 215 853 s.castro@prosensa.nl

Locations
Belgium
UZ Leuven, Campus Gasthuisberg Recruiting
Leuven, Belgium, 3000
Contact: Nathalie Goemans, Dr.    +3216343845    nathalie.goemans@uz.kuleuven.ac.be   
Contact: Liesbeth Dewaele       liesbeth.dewaele@uzleuven.be   
Principal Investigator: Nathalie Goemans, Dr.         
France
Institut de Myologie Recruiting
Paris, France, 75651
Contact: Thomas Voit, Dr.    +33142165858    t.voit@institut-myologie.org   
Contact: Valérie Doppler, Dr.       v.doppler@institut-myologie.org   
Principal Investigator: Thomas Voit, Dr.         
Italy
Policlinico Universitario Agostino Gemelli Recruiting
Rome, Italy, 00168
Contact: Eugenio Mercuri, Dr.    +390630155340    eumercuri@gmail.com   
Contact: Concetta Palermo, Dr.       palermotitti@libero.it   
Principal Investigator: Eugenio Mercuri, Dr.         
Netherlands
Leids Universitair Medisch Centrum Recruiting
Leiden, Netherlands, 2333ZA
Contact: Erik Niks, Dr.    +31715262197    E.H.Niks@lumc.nl   
Contact: Jan Verschuuren, Dr.       J.J.G.M.Verschuuren@lumc.nl   
Principal Investigator: Erik Niks, Dr.         
United Kingdom
Great Ormond Street Hospital for Children Not yet recruiting
London, United Kingdom, WC1N 3JH
Contact: Francesco Muntoni, Dr.    +442074059200    f.muntoni@ich.ucl.ac.uk   
Contact: Valeria Ricotti, Dr.       v.ricotti@ucl.ac.uk   
Principal Investigator: Francesco Muntoni, Dr.         
Institute of Genetic Medicine International Centre for Life Not yet recruiting
Newcastle, United Kingdom, NE1 3BZ
Contact: Volker Straub, Dr.    +441912418600    volker.straub@newcastle.ac.uk   
Contact: Michela Guglieri, Dr.       michela.guglieri@newcastle.ac.uk   
Principal Investigator: Volker Straub, Dr.         
Sponsors and Collaborators
Prosensa Therapeutics
Investigators
Principal Investigator: V. Straub, Prof. Institute of Genetic Medicine, Newcastle University, UK
  More Information

Additional Information:
No publications provided

Responsible Party: Prosensa Therapeutics
ClinicalTrials.gov Identifier: NCT01957059     History of Changes
Other Study ID Numbers: PRO053-CLIN-01
Study First Received: July 2, 2013
Last Updated: October 21, 2013
Health Authority: Belgium: Ethics Committee
France: Institutional Ethical Committee
Italy: Ethics Committee
Netherlands: Medical Ethics Review Committee (METC)
United Kingdom: Research Ethics Committee

Keywords provided by Prosensa Therapeutics:
DMD
Duchenne muscular dystrophy
Prosensa
Duchenne
PRO053

Additional relevant MeSH terms:
Muscular Dystrophy, Duchenne
Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on August 26, 2014