Phase 3
N=311
Dose-response Study of Efficacy and Safety of Botulinum Toxin Type A to Treat Spasticity of the Leg(s) in Cerebral Palsy
Lower Limb Spasticity Due to Cerebral Palsy
Bottom Line
View on ClinicalTrials.gov: NCT01893411 ↗Enrolled (actual)
311
Serious AEs
4.5%
Results posted
May 2017
Primary outcome: Primary: Change From Baseline in the Ashworth Scale (AS) Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle (1st IC) — -0.7; -0.66; -0.7; -0.66 Units on a scale — p== 0.65
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- IncobotulinumtoxinA (16 Units per kg body weight) (Drug); IncobotulinumtoxinA (12 Units per kg body weight) (Drug); IncobotulinumtoxinA (4 Units per kg body weight) (Drug)
- Age
- Pediatric · 2+ yrs
- Sex
- All
- Sponsor
- Merz Pharmaceuticals GmbH
- Primary completion
- Aug 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in the Ashworth Scale (AS) Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle (1st IC) |
-0.7; -0.66; -0.7; -0.66 | = 0.65 |
| PRIMARY Co-primary Variable: Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of the Primary Body Side at Day 29 (Week 4) of the First Injection Cycle |
1.53; 1.37; 1.38; 1.32 | = 0.075 |
| SECONDARY Change From Baseline in the AS Score of Plantar Flexors of the Nonprimary Body Side in Participants With Bilateral Treatment at Day 29 (Week 4) of the First (1st) and Second Injection Cycle (2nd IC) |
-0.76; -0.61; -0.6; -0.58; -0.95; -0.74 | — |
| SECONDARY Change From Baseline in the AS Score of Plantar Flexors of the Primary Body Side at Day 29 (Week 4) of the Second Injection Cycle |
-0.89; -0.82; -1.03; -0.85 | — |
| SECONDARY Changes From Baseline in AS Score of Plantar Flexors of the Primary Body Side at Day 57 (Week 8) and Day 85 (Week 12) of the First and of the Second Injection Cycle |
-0.62; -0.69; -0.74; -0.69; -0.43; -0.58 | — |
| SECONDARY Changes From Baseline in AS Score of Knee Flexors or Thigh Adductors in Participants With Unilateral Treatment at Day 29 (Week 4) of the First and of the Second Injection Cycle |
-0.6; -0.39; -0.07; -0.32; -0.64; -0.79 | — |
| SECONDARY Changes From Baseline in Modified Tardieu Scale [MTS] of Plantar Flexors of Primary Body Side at Day 29 (Week 4), Day 57 (Week 8), and Day 85 (Week 12) of the First and of the Second Injection Cycle |
-2.38; -2.56; -0.88; -2.47; -3.15; -2.63 | — |
| SECONDARY Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale [GICS] at Day 29 (Week 4) of the First and Second Injection Cycle |
1.5; 1.35; 1.36; 1.33; 1.72; 1.64 | — |
| SECONDARY Investigator's Global Impression of Change of GICS-Plantar-Flexor of Primary Body Side at Day 29 (Week 4) of the First and Second Injection Cycle |
1.53; 1.37; 1.38; 1.32; 1.43; 1.38 | — |
| SECONDARY Changes From Baseline in Gross Motor Function Measure [GMFM]-66 Score at the End of First Injection Cycle and at the End of Study Visit |
1.23; 1.64; 1.14; 1.49; 2.31; 2.46 | — |
| SECONDARY Change in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) to All Post Baseline Visits of the First and of the Second Injection Cycle |
-0.66; -1.32; -1.02; -1.61; -0.6; -0.93 | — |
| SECONDARY Time to Reinjection for Each of the Three Dose Groups for the First and Second Injection Cycle |
15.3; 15.9; 15.7; 17; 17.9; 15.5 | — |
| SECONDARY Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle |
53; 15; 18; 44; 15; 21 | — |
| SECONDARY Occurrence of Participants With TEAEs of Special Interest (TEAESIs) Overall and Per Injection Cycle |
4; 1; 0; 2; 0; 1 | — |
| SECONDARY Occurrence of Serious TEAEs (TESAEs) Overall and Per Injection Cycle |
4; 0; 3; 3; 1; 3 | — |
| SECONDARY Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and Per Injection Cycle |
7; 1; 2; 4; 1; 1 | — |
| SECONDARY Occurrence of TEAEs by Worst Intensity Overall and Per Injection Cycle |
35; 6; 14; 17; 9; 4 | — |
| SECONDARY Occurrence of TEAEs by Final Outcome Overall and Per Injection Cycle |
52; 15; 17; 0; 0; 0 | — |
| SECONDARY Occurrence of TEAEs Leading to Discontinuation Overall and Per Injection Cycle |
1; 0; 0; 0; 0; 0 | — |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- Female or male subject of 2 to 17 years of age (inclusive).
- Uni- or bilateral cerebral palsy with clinical need for uni- or bilateral LL injections with BoNT for the treatment of spasticity.
- Ashworth Scale [AS] score ≥2 in plantar flexors (at least unilaterally).
- 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.
Exclusion Criteria
- 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).
- 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.
- Hip flexion requiring BoNT injection.
Data sourced from ClinicalTrials.gov (NCT01893411). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.