A PHASE III, PROSPECTIVE, MULTICENTRE, OPEN LABEL, EXTENSION STUDY ASSESSING THE LONG TERM SAFETY AND EFFICACY OF REPEATED TREATMENT WITH DYSPORT USED IN THE TREATMENT OF LOWER LIMB SPASTICITY IN CHILDREN WITH DYNAMIC EQUINUS FOOT DEFORMITY DUE TO CEREBRAL PALSY

• Register: EUCTR
• Last refreshed on: 16 February 2015
• Main ID: EUCTR2010-019102-17-PL
• Date of registration: 31/01/2012
• Prospective Registration: Yes
• Primary sponsor: Ipsen Pharma SAS
• Public title: A PHASE III, PROSPECTIVE, MULTICENTRE, OPEN LABEL, EXTENSION STUDY ASSESSING THE LONG TERM SAFETY AND EFFICACY OF REPEATED TREATMENT WITH DYSPORT USED IN THE TREATMENT OF LOWER LIMB SPASTICITY IN CHILDREN WITH DYNAMIC EQUINUS FOOT DEFORMITY DUE TO CEREBRAL PALSY
• Scientific title: A PHASE III, PROSPECTIVE, MULTICENTRE, OPEN LABEL, EXTENSION STUDY ASSESSING THE LONG TERM SAFETY AND EFFICACY OF REPEATED TREATMENT WITH DYSPORT USED IN THE TREATMENT OF LOWER LIMB SPASTICITY IN CHILDREN WITH DYNAMIC EQUINUS FOOT DEFORMITY DUE TO CEREBRAL PALSY
• Date of first enrolment: 22/03/2012
• Target sample size: 221
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019102-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1

Countries of recruitment

Chile, Czech Republic, France, Mexico, Poland, Turkey, United States

Contacts

• Name: CT application
• Affiliation: Ipsen Pharma SAS

• Name: CT application
• Affiliation: Ipsen Pharma SAS

Key inclusion & exclusion criteria

Inclusion criteria:
All subjects must fulfil the following inclusion criteria to be eligible for the study:
(1) Completion of the double blind study (Study 141) up to the Week 12, Week 16, Week 22 or Week 28 follow up visit.
(2) Without any major protocol deviations and/or any ongoing AEs, either of which, in the opinion of the Investigator would pose an unacceptable risk to the subject were he/she to continue receiving treatment in this open label extension study.
(3) Written informed consent obtained from the child’s parent(s)/guardian(s) for this study, and assent from the child, when and where applicable.
Are the trial subjects under 18? yes
Number of subjects for this age range: 221
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects are to be excluded if any of the following apply:
(1) Major limitation in the passive range of motion at the ankle, as
defined by maximum ankle dorsiflexion measured by Tardieu
Scale XV1 of <80° (Tardieu angle) in the most affected leg to
be injected.
(2) Unwillingness or inability to comply with the protocol.
(3) Current need for surgery for spasticity of the
gastrocnemius/soleus complex (GSC) and/or hamstring
muscles (and/or tendons) in the most affected leg to be
injected.
(4) Treatment with any drug that interferes either directly or indirectly with neuromuscular function (e.g. aminoglycoside antibiotics or neuroblocking agents used during surgery e.g. curare) within the last 30 days prior to study medication or a planned treatment with such drugs.
(5) Be pregnant and/or lactating.
(6) (6) Female subjects who are not willing to use contraceptive measures throughout the course of the study if post pubertal and sexually active.
(7) An infection at the injection site(s).
(8) Planned treatment with any new investigational drug or device during the
study period.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Lower limb spasticity in children with dynamic equinus foot deformity due to cerebral palsy
MedDRA version: 16.1 Level: LLT Classification code 10024132 Term: Leg spasticity System Organ Class: 100000004852

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Dysport
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: CLOSTRIDIUM BOTULINUM TOXIN
CAS Number: 93384-43-1
Other descriptive name: BOTULINUM TOXIN TYPE A
Concentration unit: U unit(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: -AEs; all study visits
-Vital signs: at Day 1 of treatment cycle 1, and at each study visit
-Clincial laboratory parameters: at Day 1 of treatment cycle and week 4 of each treatment cycle
- Development of antibodies against BTX-A at Day 1 of Treatment Cycle 1 (, Week 4 of Treatment Cycle 2 and at the end of study or early withdrawal.
- 12-lead electrocardiograms (ECGs) at Day 1 of Treatment Cycle 1, Week 4 and at the end of study or early withdrawal.

Main Objective: The primary study objective is to assess the long term safety of repeated treatments with Dysport used in the treatment of lower limb spasticity in children with dynamic equinus foot deformity due to CP.

Secondary Objective: The secondary study objective is to assess the long term efficacy of repeated treatments with Dysport, which will include changes in the following efficacy parameters for the affected lower limb(s):
• Modified Ashworth Scale (MAS) at the ankle joint.
• Physician’s global assessment (PGA) of treatment response,
• Goal Attainment Scale (GAS),
• Tardieu Scale (TS),
• Observational Gait Scale (OGS),
• Lower limb pain,
• Duration of effects,
• Time intervals between treatments, and
• Quality of life (QoL).

Primary end point(s): Safety will be assessed through collection of AEs, vital signs (blood pressure (BP) and heart rate (HR)), clinical laboratory parameters (haematology and clinical chemistry (including alkaline phosphatase - total and bone isoenzyme, and blood glucose), development of antibodies against BTX-A (BTX-A-Abs), 12-lead electrocardiograms (ECGs). Use of prior and concomitant medications and prior lower limb surgeries will be recorded.

Secondary Outcome(s)

Secondary end point(s): • Mean change from baseline (in the double blind study) in the MAS score in the gastrocnemius-soleus complex (GSC) assessed at the ankle joint of the (most) affected lower limb.
• Proportion of subjects with at least one grade reduction in MAS score from baseline (in the double blind study) in the GSC assessed at the ankle joint of the (most) affected lower limb.
• Mean change from baseline (prior to the first injection cycle in knee flexors) in the MAS score in the knee flexors assessed at the knee joint of the (most) affected lower limb
• Mean change from baseline (prior to the first injection cycle in upper limb muscle groups) in the mean MAS score for all injected upper limb muscle groups.
• Mean PGA score.
• Mean GAS score.
• Mean change from baseline (in the double blind study) in the angle of catch (XV3), spasticity angle (X) and spasticity grade (Y), derived from the TS, in the GSC assessed at the ankle joint of the (most) affected lower limb.
• Mean change from baseline (prior to the first injection cycle in knee flexors) in the angle of catch (XV3), spasticity angle (X) and spasticity grade (Y), derived from the TS, in the knee flexors assessed at the knee joint of the (most) affected lower limb.
• Mean change from baseline (in the double blind study) in the OGS total score.
• Proportion of responders according to the OGS from baseline in the 'initial foot contact' of the OGS as assessed by video 2 dimensional (2D) motion analysis (OGS responders).
• Mean change from baseline (in the double blind study) in lower limb pain using the Faces Pain Scale (FPS).
• Time intervals between treatment injections. This endpoint will be calculated for all treatment cycles in the double blind and open label studies.
• Duration of effects for the treatment responders. This endpoint will be calculated for all treatment cycles in the double blind and open label studies.
• Mean change from baseline (in the double blind study) in the PedsQL score

Timepoint(s) of evaluation of this end point: Efficacy criteria will be evaluated at Day 1, Week 4 and Week 12 (of each treatment cycle), all visits in the observational phase, at the end of study visit or early withdrawal and at any of the additional visits when applicable (Week 16, Week 22, Week 28, Week 34 and Week 40 as described in Section 4.1.3). The Paediatric Quality of Life Inventory™ (PedsQLTM) will be assessed at Day 1 and from Week 12 to the end of each treatment cycle, and at the end of study or early withdrawal.

Secondary ID(s)

Y-55-52120-147

Source(s) of Monetary Support

Ipsen Pharma SAS