Dose-response study of efficacy and safety of Botulinum toxin type A to treat spasticity of the leg(s) in cerebral palsy

Prospective, multicenter, randomized, double-blind, parallel-group, dose-response study of three doses Xeomin® (incobotulinumtoxinA, NT 201) for the treatment of lower limb spasticity in children and adolescents (age 2 - 17 years) with cerebral palsy - TIM - Treatment with IncobotulinumtoxinA in Movement

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2012-005054-30-EE

Enrollment

300

Registered

2013-03-07

Start date

2013-04-08

Completion date

Unknown

Last updated

2018-10-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lower limb spasticity due to cerebral palsy MedDRA version: 14.1 Level: LLT Classification code 10058977 Term: Spastic paresis System Organ Class: 100000004852

Interventions

Trade Name: Xeomin Product Name: NT 201 Product Code: NT 201 Pharmaceutical Form: Powder for solution for injection INN or Proposed INN: n.a. Current Sponsor code: NT 101 Other descriptive name: CLOST

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Female or male subject of 2 to 17 years of age (inclusive). 2. Uni- or bilateral cerebral palsy with clinical need for uni- or bilateral LL injections with BoNT for the treatment of spasticity. 3. Ashworth Scale [AS] score =2 in plantar flexors (at least unilaterally). 4. Clinical need for a total dose of 16 U/kg BW NT 201 (maximum of 400 U) for the treatment of LL spasticity according to the clinical judgment of the investigator. Are the trial subjects under 18? yes Number of subjects for this age range: 300 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

Exclusion criteria: 1. Fixed contracture defined as severe restriction of the range of joint movement on passive stretch or predominant forms of muscle hypertonia other than spasticity (e.g., dystonia) in the target limb(s). 2. Surgery on pes equinus on side(s) intended to be treated with BoNT injections in this study within 12 months prior to Screening Visit (V1), in the screening period or planned for the time of participation in this study. 3. Hip flexion requiring BoNT injection. 4. Limitation of hip abduction to less than 40° or pre-diagnosed migrational percentage greater than 30.

Design outcomes

Secondary

Measure	Time frame
Secondary end point(s): - For subjects with bilateral treatment: Change from baseline in the AS score of plantar flexors of the other treated body side at Day 29 (Week 4) of the 1st and 2nd injection cycle. - Change from baseline in the AS score of plantar flexors (for subjects with bilateral pes equinus body side to be decided by investigator at screening and to be kept throughout the entire study) at Day 29 (Week 4) of the 2nd injection cycle. - Changes from baseline in AS score of plantar flexors (for subjects with bilateral pes equinus body side to be decided by investigator at screening and to be kept throughout the entire study) at Day 57 (Week 8) and Day 85 (Week 12) of the 1st and of the 2nd injection cycle. - For subjects with unilateral treatment: Changes from baseline in AS score of knee flexors or thigh adductors at Day 29 (Week 4) of the 1st and of the 2nd injection cycle. - Changes from baseline in modified Tardieu Scale [MTS] of plantar flexors (for subjects with bilateral pes equinus body side to be decided by investigator at screening and to be kept throughout the entire study) at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the 1st and of the 2nd injection cycle. - Investigator’s, Child’s/Adolescent’s, and Parent’s/Caregiver’s Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the 1st and 2nd injection cycle. - Investigator’s Global Impression of Change of Plantar Flexor Spasticity [GICS-PF] (for subjects with bilateral treatment on same body side as chosen for the primary efficacy variable) at Day 29 (Week 4) of the 1st and 2nd injection cycle. - Changes from baseline in Gross Motor Function Measure [GMFM]-66 score at the End of 1st Cycle Visit V6 and at the End of Study Visit V11. - Change in scores of pain intensity (from subjects) and pain frequency (from parent/caregiver) assessed with ‘Questionnaire on Pain caused by Spasticity [QPS]’ to all post baseline visits of the 1st and of the 2nd injection cycle. - Ti	—

Measure

Time frame

Secondary end point(s): - For subjects with bilateral treatment: Change from baseline in the AS score of plantar flexors of the other treated body side at Day 29 (Week 4) of the 1st and 2nd injection cycle. - Change from baseline in the AS score of plantar flexors (for subjects with bilateral pes equinus body side to be decided by investigator at screening and to be kept throughout the entire study) at Day 29 (Week 4) of the 2nd injection cycle. - Changes from baseline in AS score of plantar flexors (for subjects with bilateral pes equinus body side to be decided by investigator at screening and to be kept throughout the entire study) at Day 57 (Week 8) and Day 85 (Week 12) of the 1st and of the 2nd injection cycle. - For subjects with unilateral treatment: Changes from baseline in AS score of knee flexors or thigh adductors at Day 29 (Week 4) of the 1st and of the 2nd injection cycle. - Changes from baseline in modified Tardieu Scale [MTS] of plantar flexors (for subjects with bilateral pes equinus body side to be decided by investigator at screening and to be kept throughout the entire study) at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the 1st and of the 2nd injection cycle. - Investigator’s, Child’s/Adolescent’s, and Parent’s/Caregiver’s Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the 1st and 2nd injection cycle. - Investigator’s Global Impression of Change of Plantar Flexor Spasticity [GICS-PF] (for subjects with bilateral treatment on same body side as chosen for the primary efficacy variable) at Day 29 (Week 4) of the 1st and 2nd injection cycle. - Changes from baseline in Gross Motor Function Measure [GMFM]-66 score at the End of 1st Cycle Visit V6 and at the End of Study Visit V11. - Change in scores of pain intensity (from subjects) and pain frequency (from parent/caregiver) assessed with ‘Questionnaire on Pain caused by Spasticity [QPS]’ to all post baseline visits of the 1st and of the 2nd injection cycle. - Ti

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Primary

Measure	Time frame
Main Objective: The purpose of this study is to determine whether injections of Botulinum toxin type A into muscles of the leg(s) are effective in treating children/adolescents (age 2-17 years) with increased muscle tension/uncontrollable muscle stiffness (spasticity) due to cerebral palsy. ;Secondary Objective: Not applicable;Timepoint(s) of evaluation of this end point: week 4 of 1st injection cycle ;Primary end point(s): Change from baseline (Day 1) in the AS score of plantar flexors (for subjects with bilateral pes equinus body side to be decided by investigator at screening and to be kept throughout the entire study) at Day 29 (Week 4) of the 1st injection cycle. Co-primary efficacy variable (to fulfil the PMC, for US regulatory authorities only): • Investigator’s Global Impression of Change of Plantar Flexor Spasticity Scale [GICS-PF] (for subjects with bilateral treatment on same body side as chosen for the primary efficacy variable) at Day 29 (Week 4) of the 1st injection cycle.	—

Measure

Time frame

Main Objective: The purpose of this study is to determine whether injections of Botulinum toxin type A into muscles of the leg(s) are effective in treating children/adolescents (age 2-17 years) with increased muscle tension/uncontrollable muscle stiffness (spasticity) due to cerebral palsy. ;Secondary Objective: Not applicable;Timepoint(s) of evaluation of this end point: week 4 of 1st injection cycle ;Primary end point(s): Change from baseline (Day 1) in the AS score of plantar flexors (for subjects with bilateral pes equinus body side to be decided by investigator at screening and to be kept throughout the entire study) at Day 29 (Week 4) of the 1st injection cycle. Co-primary efficacy variable (to fulfil the PMC, for US regulatory authorities only): • Investigator’s Global Impression of Change of Plantar Flexor Spasticity Scale [GICS-PF] (for subjects with bilateral treatment on same body side as chosen for the primary efficacy variable) at Day 29 (Week 4) of the 1st injection cycle.

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Countries

Austria, Czech Republic, Estonia, France, Germany, Israel, Korea, Republic of, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Turkey, Ukraine

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026