PRO053-CLIN-01: A Phase I/II Study of Duchenne Muscular Dystrophy

• Research type

  Research Study

• Full 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

• IRAS ID

  125445

• Contact name

  Volker Straub

• Contact email

  volker.straub@newcastle.ac.uk

• Sponsor organisation

  Prosensa Therapeutics BV

• Eudract number

  2011-005042-35

• ISRCTN Number

  N/A

• Research summary

  The study is made of two different parts:
  Part 1 (dose escalation part) where the drug will be tested at different doses cohorts (groups) of boys will be given different doses in order to determine which dose will be the most effective and safest to give to boys with DMD
  Part 2 where the selected dose of study drug will be given for 48 weeks for safety and efficacy evaluation with an end of study visit 1 week after last treatment.
  2 cohorts of 3 subjects (in part 1) will be recruited. Each subject in the two cohorts will receive 2 single doses of PRO053 in each of 2 study periods (i.e., 4 single doses in total per subject). In each Cohort of boys will visit the study site to receive one administration of PRO053 by intravenous infusion (IV) (i.e. directly into the vein) followed by one administration by subcutaneous injection (SC) (i.e. just below the skin, using a small needle) one week later; each boy will be given a total of 4 administrations of PRO053 at 2 different doses during this part (see the diagram below).
  part 1 where 2 cohorts of 3 subjects will be recruited.
  The proposed doses are:
  1 mg/kg (Cohort 1, study period 1)
  3 mg/kg (Cohort 2, study period 1)
  6 mg/kg (Cohort 1, study period 2) and
  9 mg/kg (Cohort 2, study period 2)

  The actual doses may be amended or repeated based on emerging data from previous doses.
  It is expected that 9mg/kg will be the highest dose given. In between each dose level, there will be a review of the data (Safety Review) when Prosensa decides if it is “safe” to continue
  48week Treatment Phase
  Following completion of the second period of cohort 1 the DSMB will review the data and will advise if those subjects can continue to the treatment phase. In the absence of safety concerns, and with DSMB advice, the subjects will continue to receive 6mg/kg SC once weekly in the treatment phase. 3 additional treatment naive subjects will then be recruited to the treatment phase to start treatment on 6mg/kg.

  Likewise, following completion of the second 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. 3 additional treatment naive subjects will be recruited to start treatment at 9mg/kg.

  Dose selection phase:
  The 6 subjects who enter the treatment phase on 6 mg/kg SC will take that dose for at least 12 weeks. And the subjects on 9 mg/kg will take that dose for at least 12 weeks. Once all of the subjects have reached 12 weeks of dosing in the treatment phase the data will be reviewed by the DSMB and the optimum dose for the primary evaluation in the 48-week treatment phase will be selected. (These subjects will continue weekly dosing at their allocated dose level during this review phase). On selection of the optimum dose, 6 of the subjects will be up or down titrated to the selected dose level. Subjects will then continue weekly treatment for the remainder of the 48 weeks at the selected dose.
  Once the optimum dose is selected, an additional 30 subjects will be recruited to enter the 48 week treatment phase on the selected dose.

  Any subject who withdraws from the study for non-safety reasons prior to 6 weeks during dosing in the 48-week treatment period, may be replaced.
  At the end of the 48 weeks, all subjects will have a final study visit 1 week after the last dose. Any subjects who do not enter another study or long-term extension phase and any subjects who withdraw (assuming consent is not withdrawn) will be followed up for a minimum of 21 weeks, or as clinically indicated (if longer).
  The research study is for Ambulant boys aged at least 5 years on the day of first dosing and are able to walk for at least 230 meters in the 6 minute walking distance test. No control group is included due to the limited number of available subjects. The clinical trial will be conducted in about 20 hospitals/clinics with about 15 within the EEA and will include up to 42 patients

• REC name

  North East - Newcastle & North Tyneside 1 Research Ethics Committee

• REC reference

  13/NE/0170

• Date of REC Opinion

  23 Aug 2013

• REC opinion

  Further Information Favourable Opinion