Phase 3, blinded, multicentre study assessing efficacy and safety of Dysport for treatment of upper limb spasticity (altered skeletal muscle performance) in children

• Register: EUCTR
• Last refreshed on: 7 January 2019
• Main ID: EUCTR2010-021817-22-PL
• Date of registration: 11/03/2014
• Prospective Registration: Yes
• Primary sponsor: IPSEN INNOVATION
• Public title: Phase 3, blinded, multicentre study assessing efficacy and safety of Dysport for treatment of upper limb spasticity (altered skeletal muscle performance) in children
• Scientific title: A PHASE III, MULTICENTRE, DOUBLE BLIND, PROSPECTIVE, RANDOMISED, CONTROLLED, MULTIPLE TREATMENT STUDY ASSESSING EFFICACY AND SAFETY OF DYSPORT USED IN THE TREATMENT OF UPPER LIMB SPASTICITY IN CHILDREN
• Date of first enrolment: 28/04/2014
• Target sample size: 210
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-021817-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: two doses of Dysport (8 units (U)/kg and 16 U/kg) compared to Dysport 2 U/kg; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Brazil, Bulgaria, Chile, Colombia, Czech Republic, France, Georgia, Israel, Lithuania, Mexico, Poland, Portugal, Russian Federation, South Africa, Spain, Turkey, United States

Contacts

• Name: Christine Seymour
• Affiliation: IPSEN INNOVATION

• Name: Christine Seymour
• Affiliation: IPSEN INNOVATION

Key inclusion & exclusion criteria

Inclusion criteria:
((1) Signed informed consent obtained from the child’s parent(s)/guardian(s) and, if applicable, a signed assent from the child.
(2) Be from 2 to 17 years of age, inclusive.
(3) Body weight of 10 kg or more at the baseline visit.
(4) Have a diagnosis of CP, as defined by Rosenbaum.
(5) Have increased muscle tone/spasticity in at least one upper limb.
(6) Have a MAS score =2 in the upper limb primary targeted muscle group (elbow flexors or wrist flexors) of the study limb (the limb to be injected in the first treatment) at the baseline visit.
(7) Be classified as Gross Motor Function Classification System Level 1 to 4.
(8) If undergoing therapy, such as physiotherapy, occupational therapy, or use of splints and/or orthoses, therapy must have been initiated at least 30 days prior to the baseline visit and agreed to continue the therapy throughout the study and at the minimum, up to Week 16 following the first treatment administration.

Are the trial subjects under 18? yes
Number of subjects for this age range: 210
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:
(1) Fixed myocontracture in the primary targeted muscle group (elbow flexors or wrist flexors) of the study limb defined as having an available range of motion angle of <40°, regardless of the starting and finishing angles, measured at the Tardieu Scale (TS) slow (XV1) speed at the baseline visit. (Available range for wrist flexors should be measured without holding the fingers and allowing free finger flexion).
(2) Subjects likely to be treated with BTX in the lower limb(s) and/or the nonstudy upper limb before Treatment 2 of the study.
(3) Inadequate washout from previous BTX injection of any serotype for any condition:
• Within 6 months prior to the baseline visit in the study limb,
or
• Within 3 months prior to the baseline visit in any other part of the body.
(4) Subjects who require BTX treatment in a single muscle group in the study limb in Treatment 1.
(5) Severe athetoid or dystonic movements in the study limb.
(6) Previous or planned surgery for spasticity in the primary targeted muscle group(s) of the study limb.
(7) Previous injection of alcohol and/or phenol within 1 year prior to the baseline visit affecting the study limb wrist flexors and/or elbow flexors selected for injection in Treatment 1.
(8) 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 treatment.
(9) Are pregnant and/or lactating.
(10) Female subjects not willing to use contraceptive measures throughout the course of the study if postpubertal and sexually active.
(11) Inability or unwillingness to comply with the protocol.
(12) Subjects with any clinical (or sub-clinical) evidence of marked defective neuromuscular transmission (e.g. Lambert-Eaton syndrome or myasthenia gravis) or persistent clinically significant neuromuscular disorders.
(13) Known sensitivity to BTX or to any of the components in the formulation or allergy to cow’s milk protein.
(14) An infection at the injection site(s).
(15) Previous rhizotomy less than 6 months prior to the baseline visit or rhizotomy planned/anticipated during the course of the study.
(16) Subjects treated or likely to be treated with intrathecal baclofen within 30 days prior to the baseline visit or during the course of the study.
(17) Treatment with a new investigational drug within 30 days prior to the baseline visit or scheduled to receive such a drug during the course of the study.
(18) Subjects with a history of aspiration or conditions which put them at risk of aspiration, such as severe dysphagia.
(19) Concurrent or history of frequent lower respiratory tract infections, aspiration pneumonia, or, as judged by the Investigator, has compromised respiratory function.
(20) Any known medical condition, laboratory or diagnostic procedure finding, which might compromise compliance with the objectives and procedures of this protocol or preclude administration of botulinum toxin type A (BTX-A), as judged by the Investigator.
(21) Any uncontrolled clinically significant medical condition other than CP.


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

Health Condition(s) or Problem(s) studied

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

Upper limb spasticity in children
MedDRA version: 20.0 Level: LLT Classification code 10048970 Term: Arm spasticity System Organ Class: 100000004852

Intervention(s)

Trade Name: Dysport
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: CLOSTRIDIUM BOTULINUM TOXIN TYPE A
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)

Primary end point(s): Primary Efficacy Endpoint:
Mean change from Baseline to Treatment 1, Week 6 in MAS score in the Treatment 1 primary targeted muscle group (elbow flexors or wrist flexors).

Main Objective: The primary study objective is to assess the efficacy of two doses of Dysport (8 U/kg and 16 U/kg) compared to Dysport 2 U/kg used in the treatment of upper limb spasticity in children with CP following a single treatment.

Timepoint(s) of evaluation of this end point: week 6

Secondary Objective: The secondary study objective is to assess the long term safety of multiple treatments of Dysport used in this study population.

The tertiary study objectives will evaluate the long term efficacy of Dysport, its effect on pain in the study limb and quality of life (QoL) following multiple treatments.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: week 6

Secondary end point(s): Mean PGA score at Treatment 1, Week 6.
Mean GAS score at Treatment 1, Week 6.

Secondary ID(s)

2010-021817-22-CZ

Y-52-52120-153

Source(s) of Monetary Support

IPSEN INNOVATION