Lower Limb and Combined Lower Limb and Upper Limb Spasticity Due to Cerebral Palsy
Conditions
Brief summary
The purpose of this study is to determine whether injections of Botulinum toxin type A into muscles of the leg(s) or of leg(s) and one arm are safe in treating children/adolescents (age 2-17 years) long-term with increased muscle tension/uncontrollable muscle stiffness (spasticity) due to cerebral palsy.
Interventions
DRUGIncobotulinumtoxinA (16-20 Units per kg body weight)
Active ingredient: Clostridium Botulinum neurotoxin type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl); Total dose per injection cycle: up to 500 units; Mode of administration: intramuscular injection into spastic muscles.
Sponsors
Merz Pharmaceuticals GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Main clinical inclusion criteria for completers of study MRZ60201\_3070\_1: * Subject with lower limb \[LL\] spasticity who completed lead-in study MRZ60201\_3070\_1 in any of the three dose groups with duration of both injection cycles between 12 and 16 weeks. * Ashworth scale \[AS\] score ≥2 in plantar flexors (at least unilaterally). For subjects with an AS score of 1, the investigator has to decide on the clinical need for reinjection. * Clinical need for spasticity treatment with NT 201 according to the clinical judgment of the investigator for: Unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into pes equinus and need for additional 8 U/kg BW NT 201 (maximum of 200 U) for treatment of clinical pattern flexed knee or adducted thigh (ipsilateral) or bilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into pes equinus on each side. No treatment of other clinical patterns is allowed. Main clinical inclusion criteria for subjects who did not participate in MRZ60201\_3070\_1: * Female or male subject of 2 to 17 years age (inclusive). * Uni- or bilateral CP with clinical need for BoNT injection to treat limb spasticity. * AS score ≥ 2 in plantar flexors (at least unilaterally). * Clinical need according to the clinical judgment of the investigator in one out of four treatment combinations: 1. For LL(s) treatment only (Gross Motor Function Classification System \[GMFCS\] levels IV): Unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into pes equinus, and 8 U/kg BW NT 201 (maximum of 200 U) into flexed knee or adducted thigh or bilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into each pes equinus (AS score ≥ 2 on both sides). 2. For combined unilateral UL and unilateral LL, (GMFCS levels I-III): Unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into pes equinus, and 8 U/kg BW NT 201 (maximum of 200 U) into flexed knee or adducted thigh plus Unilateral treatment of UL spasticity with 4 U/kg BW NT 201 (maximum of 100 U) into flexed elbow, flexed wrist, clenched fist, thumb in palm and/or pronated forearm. 3. For combined unilateral UL and unilateral LL (GMFCS level IV-V): Unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum 200 U) into pes equinus, and 4 U/kg BW NT201 (maximum 100 U) into flexed knee or adducted thigh plus unilateral treatment of UL spasticity with 4 U/kg BW NT 201 (maximum of 100 U) into flexed elbow, flexed wrist, clenched fist, thumb in palm and/or pronated forearm. 4. For combined unilateral UL and bilateral LL (GMFCS levels I-III): Bilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into each pes equinus (AS score ≥ 2 on both sides) plus unilateral treatment of UL spasticity with 4 U/kg BW NT 201 (maximum of 100 U) into flexed elbow, flexed wrist, clenched fist, thumb in palm and/or pronated forearm.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | From the timepoint of first injection up to end of study visit (Week 50-66) | TEAEs are events observed from the time point of first injection until end of study visit (Week 50-66). Values reported here refer to the number of participants affected. |
| Occurrence of Treatment Emergent Adverse Events of Special Interest (TEAESI) Overall and Per Injection Cycle | From the timepoint of first injection until end of study visit (Week 50-66) | TEAEs occurring after treatment that were thought to possibly indicate toxin spread throughout the trial conduct are defined as TEAESI. Values reported here refer to the number of participants affected. |
| Occurrence of Treatment-emergent Serious Adverse Events (TESAEs) Overall and Per Injection Cycle | From the timepoint of first injection until end of study visit (Week 50-66) | TESAEs are events observed from the time point of first injection until end of study visit (Week 50-66). Values reported here refer to the number of participants affected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of Left and Right PF at Day 29 (Week 4) of Each Injection Cycle | Day 29 (Week 4) of 1st, 2nd, 3rd and 4th injection cycle | The GICS are global outcomes to assess the impression of change due to treatment. GICS were assessed by the investigator, by the participant (if feasible) and by parents'/caregiver (if applicable). GICS is a 7-Point Likert Scale ranging from +3 (very much improved function) to -3 (very much worse function). For participants with bilateral pes equinus, the body side for efficacy analysis that is primary body side was decided by investigator at screening and was kept throughout the entire study. |
| Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Baseline (Day 1, Visit [V] 2) to all other visits (V3, V4, V5, V6, V7, V8, V9, V10, and V11); From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC cycle only) and Day 99 (Week 14) of the respective IC | The MTS assesses spastic muscle tone by subtraction of two angles measured at different conditions of passive muscle stretch. R2 is the angle of passive range of motion with a passive movement at slow speed. R1 is the angle where a catch-and-release or clonus can be triggered at the fastest possible speed. Score values represent the measured (R2-R1) difference, that is, the dynamic tone component of the examined muscle(s). Decreases of (R2-R1) represent reductions in the dynamic component of spasticity, that is, improvement of dynamic muscle spasticity. V3 = Week 4 of 1st IC; V4 = Week 8 of 1st IC; V5 = Day 1 of 2nd IC; V6 = Week 4 of 2nd IC; V7 = Day 1 of 3rd IC; V8 = Week 4 of 3rd IC; V9 = Day 1 of 4th IC; V10 = Week 4 of 4th IC; V11 = Week 14 of 4th IC = end of study visit. |
| Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | Day 99 (Week 14) of 1st, 2nd, 3rd and 4th injection cycle | The investigator's global assessment of tolerability was assessed on a 4-point ordinal scale where 1 = very good, 2 = good, 3 = moderate, and 4 = poor. Results for Day 99 (Week 14) of 4th injection cycles were collected at the end of study visit. |
| Changes in Gross Motor Function Measure (GMFM)-66 Score From Baseline to All Injection Visits and End of Study | Baseline to Day 1 of 2nd (V5), 3rd (V7), 4th (V9) IC and End of study (Week 44-68) (V11) | The GMFM-66 is a standardized observational 66-item instrument designed and validated to measure change in gross motor function over time in participants with cerebral palsy. Score values represent the total GMFM-66 score. Total GMFM scores range from 0 (worst) to 100 (best). |
| Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Baseline (Day 1, Visit [V] 2) to all other visits (V3, V4, V5, V6, V7, V8, V9, V10, and V11); From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC cycle only) and Day 99 (Week 14) of the respective IC | The questionnaire on pain caused by Spasticity (QPS) is a participant-reported outcome for children and adolescents (2-17 years) with cerebral palsy on spasticity-related pain. Pain intensity (from participants) and pain frequency (from parent/caregiver) to be assessed with QPS. The QPS total score for pain intensity ranges from 0 ('No Hurt') to 10 ('Hurt Worst'). The QPS total score for the observed pain frequency ranges from 0 (Never) to 4 (Always). V3 = Week 4 of 1st IC; V4 = Week 8 of 1st IC; V5= Day 1 of 2nd IC; V6 = Week 4 of 2nd IC; V7 = Day 1 of 3rd IC; V8 = Week 4 of 3rd IC; V9 = Day 1 of 4th IC; V10 = Week 4 of 4th IC; V11 = Week 14 of 4th IC = end of study visit. |
| Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Baseline (Day 1, Visit [V] 2) to all other visits (V3, V4, V5, V6, V7, V8, V9, V10, and V11); From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle only) and Day 99 (Week 14) of the respective Injection Cycle | The Ashworth Scale (AS) is a well-known and commonly used scale in clinical trials with spasticity. In spastic muscles the resistance to passive movement is assessed. It is a 5-point scale that ranges from 0 (= no increase in tone) to 4 (=limb rigid in flexion or extension). For participants with bilateral pes equinus, the body side for efficacy analysis that is, primary body side was decided by investigator at screening and was kept throughout the entire study. V3 = Week 4 of 1st Injection Cycle; V4 = Week 8 of 1st Injection Cycle; V5 = Day 1 of 2nd Injection Cycle; V6= Week 4 of 2nd Injection Cycle; V7 = Day 1 of 3rd Injection Cycle; V8 = Week 4 of 3rd Injection Cycle; V9 = Day 1 of 4th Injection Cycle; V10 = Week 4 of 4th Injection Cycle; V11= Week 14th of 4th Injection Cycle = end of study visit. |
| Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle | Day 29 (Week 4) of 1st, 2nd, 3rd and 4th injection cycle | The GICS are global outcomes to assess the impression of change due to treatment. GICS were assessed by the investigator, by the participant (if feasible) and by parents'/caregiver (if applicable). GICS is 7-Point Likert Scale ranging from +3 (very much improved function) to -3 (very much worse function). |
Countries
Austria, Czechia, Estonia, Germany, Israel, Poland, Romania, Russia, Slovakia, South Korea, Turkey (Türkiye), Ukraine
Participant flow
Pre-assignment details
A total of 391 participants were screened, of which 370 participants were enrolled and treated. Of these, 124 participants were recruited from the lead-in study (62, 29 and 33 participants from the IncobotulinumtoxinA high, mid and low dose group respectively of study MRZ60201\_3070\_1 \[2012-005054-30\]) and 246 participants were newly recruited.
Participants by arm
| Arm | Count |
|---|---|
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) Participants received total doses of 16 to 20 unit per kilogram (U/kg) body weight of IncobotulinumtoxinA (Xeomin) with a maximum of 400 to 500 units per injection treatment via intramuscular injection into spastic muscles on Day 1 of 4 treatment cycles (12 to 16 weeks treatment per each cycle). The higher dose could only be administered to participants with GMFCS-E&R levels I to III. | 370 |
| Total | 370 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Lack of Efficacy | 8 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Re-injection criteria not met; others | 13 |
| Overall Study | Withdrawal by Subject | 20 |
Baseline characteristics
| Characteristic | 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) |
|---|---|
| Age, Continuous | 6.2 years STANDARD_DEVIATION 4.1 |
| Age, Customized Adolescents (12-17 years) | 53 Participants |
| Age, Customized Children (2-11 years) | 317 Participants |
| Region of Enrollment Austria | 1 participants |
| Region of Enrollment Czechia | 1 participants |
| Region of Enrollment Estonia | 5 participants |
| Region of Enrollment Germany | 1 participants |
| Region of Enrollment Israel | 1 participants |
| Region of Enrollment Poland | 67 participants |
| Region of Enrollment Romania | 22 participants |
| Region of Enrollment Russia | 33 participants |
| Region of Enrollment Slovakia | 5 participants |
| Region of Enrollment South Korea | 59 participants |
| Region of Enrollment Turkey | 5 participants |
| Region of Enrollment Ukraine | 170 participants |
| Sex: Female, Male Female | 150 Participants |
| Sex: Female, Male Male | 220 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 370 |
| other Total, other adverse events | 20 / 370 |
| serious Total, serious adverse events | 16 / 370 |
Outcome results
Primary
Occurrence of Treatment Emergent Adverse Events of Special Interest (TEAESI) Overall and Per Injection Cycle
TEAEs occurring after treatment that were thought to possibly indicate toxin spread throughout the trial conduct are defined as TEAESI. Values reported here refer to the number of participants affected.
Time frame: From the timepoint of first injection until end of study visit (Week 50-66)
Population: The SES was the subset of all participants treated with IP at least once.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment Emergent Adverse Events of Special Interest (TEAESI) Overall and Per Injection Cycle | 1st Injection Cycle | 1 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment Emergent Adverse Events of Special Interest (TEAESI) Overall and Per Injection Cycle | 2nd Injection Cycle | 2 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment Emergent Adverse Events of Special Interest (TEAESI) Overall and Per Injection Cycle | 3rd Injection Cycle | 1 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment Emergent Adverse Events of Special Interest (TEAESI) Overall and Per Injection Cycle | 4th Injection Cycle | 0 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment Emergent Adverse Events of Special Interest (TEAESI) Overall and Per Injection Cycle | Overall Period | 3 participants |
Primary
Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
TEAEs are events observed from the time point of first injection until end of study visit (Week 50-66). Values reported here refer to the number of participants affected.
Time frame: From the timepoint of first injection up to end of study visit (Week 50-66)
Population: The SES was the subset of all participants treated with IP at least once.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | 1st Injection Cycle | 53 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | 2nd Injection Cycle | 44 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | 3rd Injection Cycle | 26 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | 4th Injection Cycle | 31 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle | Overall Period | 109 participants |
Primary
Occurrence of Treatment-emergent Serious Adverse Events (TESAEs) Overall and Per Injection Cycle
TESAEs are events observed from the time point of first injection until end of study visit (Week 50-66). Values reported here refer to the number of participants affected.
Time frame: From the timepoint of first injection until end of study visit (Week 50-66)
Population: The SES was the subset of all participants treated with IP at least once.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment-emergent Serious Adverse Events (TESAEs) Overall and Per Injection Cycle | 1st Injection Cycle | 6 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment-emergent Serious Adverse Events (TESAEs) Overall and Per Injection Cycle | 2nd Injection Cycle | 5 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment-emergent Serious Adverse Events (TESAEs) Overall and Per Injection Cycle | 3rd Injection Cycle | 5 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment-emergent Serious Adverse Events (TESAEs) Overall and Per Injection Cycle | 4th Injection Cycle | 1 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Occurrence of Treatment-emergent Serious Adverse Events (TESAEs) Overall and Per Injection Cycle | Overall Period | 16 participants |
Secondary
Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection
The questionnaire on pain caused by Spasticity (QPS) is a participant-reported outcome for children and adolescents (2-17 years) with cerebral palsy on spasticity-related pain. Pain intensity (from participants) and pain frequency (from parent/caregiver) to be assessed with QPS. The QPS total score for pain intensity ranges from 0 ('No Hurt') to 10 ('Hurt Worst'). The QPS total score for the observed pain frequency ranges from 0 (Never) to 4 (Always). V3 = Week 4 of 1st IC; V4 = Week 8 of 1st IC; V5= Day 1 of 2nd IC; V6 = Week 4 of 2nd IC; V7 = Day 1 of 3rd IC; V8 = Week 4 of 3rd IC; V9 = Day 1 of 4th IC; V10 = Week 4 of 4th IC; V11 = Week 14 of 4th IC = end of study visit.
Time frame: Baseline (Day 1, Visit [V] 2) to all other visits (V3, V4, V5, V6, V7, V8, V9, V10, and V11); From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC cycle only) and Day 99 (Week 14) of the respective IC
Population: The FAS was the subset of participants in the SES for whom at least a baseline value (Day 1 of the first cycle, Visit 2) of AS score of PF was available. For participants from lead-in study at least one post-baseline value was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Participants Baseline (V2) to V3 | -0.6 units on a scale | Standard Deviation 1.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Participants Baseline (V2) to V4 | -0.5 units on a scale | Standard Deviation 2 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Participants Baseline (V2) to V5 | -0.5 units on a scale | Standard Deviation 1.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Participants Baseline (V2) to V6 | -0.9 units on a scale | Standard Deviation 1.9 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Participants Baseline (V2) to V7 | -0.7 units on a scale | Standard Deviation 1.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Participants Baseline (V2) to V8 | -1.1 units on a scale | Standard Deviation 1.9 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Participants Baseline (V2) to V9 | -0.8 units on a scale | Standard Deviation 1.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Participants Baseline (V2) to V10 | -1.2 units on a scale | Standard Deviation 2 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Participants Baseline (V2) to V11 | -1 units on a scale | Standard Deviation 1.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Participants 2nd IC: Day 1 to Day 29 | -0.4 units on a scale | Standard Deviation 1.4 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Participants 2nd IC: Day 1 to Day 99 | -0.2 units on a scale | Standard Deviation 1.2 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Participants 3rd IC: Day 1 to Day 29 | -0.4 units on a scale | Standard Deviation 1.2 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Participants 3rd IC: Day 1 to Day 99 | -0.1 units on a scale | Standard Deviation 0.9 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Participants 4th IC: Day 1 to Day 29 | -0.4 units on a scale | Standard Deviation 1.3 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Participants 4th IC: Day 1 to Day 99 | -0.3 units on a scale | Standard Deviation 1 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Parent/Caregiver Baseline (V2) to V3 | -0.5 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Parent/Caregiver Baseline (V2) to V4 | -0.4 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Parent/Caregiver Baseline (V2) to V5 | -0.3 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Parent/Caregiver Baseline (V2) to V6 | -0.7 units on a scale | Standard Deviation 0.9 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Parent/Caregiver Baseline (V2) to V7 | -0.4 units on a scale | Standard Deviation 0.9 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Parent/Caregiver Baseline (V2) to V8 | -0.7 units on a scale | Standard Deviation 1 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Parent/Caregiver Baseline (V2) to V9 | -0.5 units on a scale | Standard Deviation 0.9 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Parent/Caregiver Baseline (V2) to V10 | -0.8 units on a scale | Standard Deviation 1 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Parent/Caregiver Baseline (V2) to V11 | -0.6 units on a scale | Standard Deviation 0.9 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Parent/Caregiver 2nd IC:Day 1 to Day 29 | -0.4 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Parent/Caregiver 2nd IC:Day 1 to Day 99 | -0.1 units on a scale | Standard Deviation 0.6 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Parent/Caregiver 3rd IC: Day 1 to Day 29 | -0.3 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Parent/Caregiver 3rd IC: Day 1 to Day 99 | -0.1 units on a scale | Standard Deviation 0.5 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Parent/Caregiver 4th IC: Day 1 to Day 29 | -0.3 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Change in Scores of Pain Intensity (From Participants) and Frequency (From Parent/Caregiver) From Baseline to All Visits, From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC Cycle Only) and Day 99 (Week 14) of Respective Injection | Parent/Caregiver 4th IC: Day 1 to Day 99 | -0.1 units on a scale | Standard Deviation 0.6 |
Secondary
Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle
The Ashworth Scale (AS) is a well-known and commonly used scale in clinical trials with spasticity. In spastic muscles the resistance to passive movement is assessed. It is a 5-point scale that ranges from 0 (= no increase in tone) to 4 (=limb rigid in flexion or extension). For participants with bilateral pes equinus, the body side for efficacy analysis that is, primary body side was decided by investigator at screening and was kept throughout the entire study. V3 = Week 4 of 1st Injection Cycle; V4 = Week 8 of 1st Injection Cycle; V5 = Day 1 of 2nd Injection Cycle; V6= Week 4 of 2nd Injection Cycle; V7 = Day 1 of 3rd Injection Cycle; V8 = Week 4 of 3rd Injection Cycle; V9 = Day 1 of 4th Injection Cycle; V10 = Week 4 of 4th Injection Cycle; V11= Week 14th of 4th Injection Cycle = end of study visit.
Time frame: Baseline (Day 1, Visit [V] 2) to all other visits (V3, V4, V5, V6, V7, V8, V9, V10, and V11); From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle only) and Day 99 (Week 14) of the respective Injection Cycle
Population: The full analysis set (FAS) was the subset of participants in the SES for whom at least a baseline value (Day 1 of the first cycle, Visit 2) of AS score of PF was available. For participants from lead-in study at least one post-baseline value was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V3 | -0.8 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V4 | -0.7 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V5 | -0.2 units on a scale | Standard Deviation 0.5 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V6 | -1.1 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V7 | -0.3 units on a scale | Standard Deviation 0.6 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V8 | -1.2 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V9 | -0.3 units on a scale | Standard Deviation 0.6 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V10 | -1.3 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V11 | -0.9 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF 2nd Injection Cycle: Day 1 to Day 29 | -0.9 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF 2nd Injection Cycle: Day 1 to Day 99 | -0.1 units on a scale | Standard Deviation 0.4 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF 3rd Injection Cycle: Day 1 to Day 29 | -0.9 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF 3rd Injection Cycle: Day 1 to Day 99 | -0.1 units on a scale | Standard Deviation 0.4 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF 4th Injection Cycle: Day 1 to Day 29 | -1 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF 4th Injection Cycle: Day 1 to Day 99 | -0.6 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V3 | -0.8 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V4 | -0.7 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V5 | -0.2 units on a scale | Standard Deviation 0.5 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V6 | -1 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V7 | -0.2 units on a scale | Standard Deviation 0.5 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V8 | -1.2 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V9 | -0.3 units on a scale | Standard Deviation 0.5 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V10 | -1.2 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V11 | -0.9 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF 2nd Injection Cycle: Day 1 to Day 29 | -0.8 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF 2nd Injection Cycle: Day 1 to Day 99 | -0.1 units on a scale | Standard Deviation 0.4 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF 3rd Injection Cycle: Day 1 to Day 29 | -1 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF 3rd Injection Cycle: Day 1 to Day 99 | 0 units on a scale | Standard Deviation 0.4 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF 4th Injection Cycle: Day 1 to Day 29 | -1 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in AS Score of Left and Right Plantar Flexors (PF) From Baseline to All Other Visits, From Day 1 of Each Injection Cycle to Day 29 (Week 4), Day 57 (Week 8, 1st Injection Cycle Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF 4th Injection Cycle: Day 1 to Day 99 | -0.6 units on a scale | Standard Deviation 0.7 |
Secondary
Changes in Gross Motor Function Measure (GMFM)-66 Score From Baseline to All Injection Visits and End of Study
The GMFM-66 is a standardized observational 66-item instrument designed and validated to measure change in gross motor function over time in participants with cerebral palsy. Score values represent the total GMFM-66 score. Total GMFM scores range from 0 (worst) to 100 (best).
Time frame: Baseline to Day 1 of 2nd (V5), 3rd (V7), 4th (V9) IC and End of study (Week 44-68) (V11)
Population: The FAS was the subset of participants in the SES for whom at least a baseline value (Day 1 of the first cycle, Visit 2) of AS score of PF was available. For participants from lead-in study at least one post-baseline value was available. Therefore all participants from lead-in study were included in FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Gross Motor Function Measure (GMFM)-66 Score From Baseline to All Injection Visits and End of Study | Baseline (V2) to V5 | 1.5 units on a scale | Standard Deviation 3.2 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Gross Motor Function Measure (GMFM)-66 Score From Baseline to All Injection Visits and End of Study | Baseline (V2) to V7 | 2.6 units on a scale | Standard Deviation 4 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Gross Motor Function Measure (GMFM)-66 Score From Baseline to All Injection Visits and End of Study | Baseline (V2) to V9 | 3.8 units on a scale | Standard Deviation 5.1 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Gross Motor Function Measure (GMFM)-66 Score From Baseline to All Injection Visits and End of Study | Baseline (V2) to V11 | 4.8 units on a scale | Standard Deviation 5.9 |
Secondary
Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle
The MTS assesses spastic muscle tone by subtraction of two angles measured at different conditions of passive muscle stretch. R2 is the angle of passive range of motion with a passive movement at slow speed. R1 is the angle where a catch-and-release or clonus can be triggered at the fastest possible speed. Score values represent the measured (R2-R1) difference, that is, the dynamic tone component of the examined muscle(s). Decreases of (R2-R1) represent reductions in the dynamic component of spasticity, that is, improvement of dynamic muscle spasticity. V3 = Week 4 of 1st IC; V4 = Week 8 of 1st IC; V5 = Day 1 of 2nd IC; V6 = Week 4 of 2nd IC; V7 = Day 1 of 3rd IC; V8 = Week 4 of 3rd IC; V9 = Day 1 of 4th IC; V10 = Week 4 of 4th IC; V11 = Week 14 of 4th IC = end of study visit.
Time frame: Baseline (Day 1, Visit [V] 2) to all other visits (V3, V4, V5, V6, V7, V8, V9, V10, and V11); From Day 1 of Each IC to Day 29 (Week 4), Day 57 (Week 8, 1st IC cycle only) and Day 99 (Week 14) of the respective IC
Population: The FAS was the subset of participants in the SES for whom at least a baseline value (Day 1 of the first cycle, Visit 2) of AS score of PF was available. For participants from lead-in study at least one post-baseline value was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline(V2) to V3 | -1.4 Degrees | Standard Deviation 10.6 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V4 | -1.8 Degrees | Standard Deviation 9.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V5 | -1 Degrees | Standard Deviation 7.1 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V6 | -1 Degrees | Standard Deviation 12.3 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V7 | -1.7 Degrees | Standard Deviation 8.1 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V8 | -0.5 Degrees | Standard Deviation 13.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V9 | -2.5 Degrees | Standard Deviation 8.1 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V10 | -1.1 Degrees | Standard Deviation 14.6 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF Baseline (V2) to V11 | -2.8 Degrees | Standard Deviation 10.9 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF 2nd IC: Day 1 to Day 29 | 0 Degrees | Standard Deviation 11.1 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF 2nd IC: Day 1 to Day 99 | -0.7 Degrees | Standard Deviation 5.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF 3rd IC: Day 1 to Day 29 | 1.2 Degrees | Standard Deviation 10.9 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF 3rd IC: Day 1 to Day 99 | -1 Degrees | Standard Deviation 5.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF 4th IC: Day 1 to Day 29 | 1.5 Degrees | Standard Deviation 11.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Left PF 4th IC: Day 1 to Day 99 | 0 Degrees | Standard Deviation 7.9 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V3 | -1.3 Degrees | Standard Deviation 10.6 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V4 | -2.1 Degrees | Standard Deviation 9.3 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V5 | -1.3 Degrees | Standard Deviation 7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V6 | -0.7 Degrees | Standard Deviation 12.4 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V7 | -2.2 Degrees | Standard Deviation 8.3 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V8 | -0.1 Degrees | Standard Deviation 13.9 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V9 | -2.6 Degrees | Standard Deviation 8.5 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V10 | -0.7 Degrees | Standard Deviation 14.4 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF Baseline (V2) to V11 | -2.6 Degrees | Standard Deviation 11.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF 2nd IC: Day 1 to Day | 0.6 Degrees | Standard Deviation 11.1 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF 2nd IC: Day 1 to Day 99 | -1 Degrees | Standard Deviation 7.2 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF 3rd IC: Day 1 to Day 29 | 2.1 Degrees | Standard Deviation 11.5 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF 3rd IC: Day 1 to Day 99 | -0.5 Degrees | Standard Deviation 6.2 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF 4th IC: Day 1 to Day 29 | 1.9 Degrees | Standard Deviation 11.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Changes in Modified Tardieu Scale (MTS) of Left and Right PF From Baseline to All Other Visits, From Day 1 of Each Injection Cycle (IC) to Day 29 (Week 4), Day 57 (Week 8, 1st IC Only) and Day 99 (Week 14) of the Respective Injection Cycle | Right PF 4th IC: Day 1 to Day 99 | 0.4 Degrees | Standard Deviation 9.3 |
Secondary
Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle
The GICS are global outcomes to assess the impression of change due to treatment. GICS were assessed by the investigator, by the participant (if feasible) and by parents'/caregiver (if applicable). GICS is 7-Point Likert Scale ranging from +3 (very much improved function) to -3 (very much worse function).
Time frame: Day 29 (Week 4) of 1st, 2nd, 3rd and 4th injection cycle
Population: The FAS was the subset of participants in the SES for whom at least a baseline value (Day 1 of the first cycle, Visit 2) of AS score of PF was available. For participants from lead-in study at least one post-baseline value was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle | Investigator, Day 29 of 1st Injection Cycle | 1.7 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle | Investigator, Day 29 of 2nd Injection Cycle | 1.8 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle | Investigator, Day 29 of 3rd Injection Cycle | 1.9 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle | Investigator, Day 29 of 4th Injection Cycle | 2 units on a scale | Standard Deviation 0.9 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle | Participant, Day 29 of 1st Injection Cycle | 1.6 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle | Participant, Day 29 of 2nd Injection Cycle | 1.7 units on a scale | Standard Deviation 1 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle | Participant, Day 29 of 3rd Injection Cycle | 1.7 units on a scale | Standard Deviation 0.9 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle | Participant, Day 29 of 4th Injection Cycle | 1.8 units on a scale | Standard Deviation 0.9 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle | Parent/Caregiver, Day 29 of 1st Injection Cycle | 1.6 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle | Parent/Caregiver, Day 29 of 2nd Injection Cycle | 1.8 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle | Parent/Caregiver, Day 29 of 3rd Injection Cycle | 1.8 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's, Child's/Adolescent's, and Parent's/Caregiver's Global Impression of Change Scale (GICS) at Day 29 (Week 4) of Each Injection Cycle | Parent/Caregiver, Day 29 of 4th Injection Cycle | 1.9 units on a scale | Standard Deviation 0.9 |
Secondary
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
The investigator's global assessment of tolerability was assessed on a 4-point ordinal scale where 1 = very good, 2 = good, 3 = moderate, and 4 = poor. Results for Day 99 (Week 14) of 4th injection cycles were collected at the end of study visit.
Time frame: Day 99 (Week 14) of 1st, 2nd, 3rd and 4th injection cycle
Population: The SES was the subset of all participants treated with IP at least once.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 2nd Injection Cycle: Poor | 4 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 1st Injection Cycle: Very Good | 203 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 1st Injection Cycle: Good | 119 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 1st Injection Cycle: Moderate | 23 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 1st Injection Cycle: Poor | 5 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 2nd Injection Cycle: Very Good | 225 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 2nd Injection Cycle: Good | 87 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 2nd Injection Cycle: Moderate | 24 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 3rd Injection Cycle: Very Good | 223 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 3rd Injection Cycle: Good | 74 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 3rd Injection Cycle: Moderate | 17 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 3rd Injection Cycle: Poor | 9 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 4th Injection Cycle: Very Good | 241 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 4th Injection Cycle: Good | 76 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 4th Injection Cycle: Moderate | 16 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 4th Injection Cycle: Poor | 8 participants |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle | 4th Injection Cycle: Not assessed | 29 participants |
Secondary
Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of Left and Right PF at Day 29 (Week 4) of Each Injection Cycle
The GICS are global outcomes to assess the impression of change due to treatment. GICS were assessed by the investigator, by the participant (if feasible) and by parents'/caregiver (if applicable). GICS is a 7-Point Likert Scale ranging from +3 (very much improved function) to -3 (very much worse function). For participants with bilateral pes equinus, the body side for efficacy analysis that is primary body side was decided by investigator at screening and was kept throughout the entire study.
Time frame: Day 29 (Week 4) of 1st, 2nd, 3rd and 4th injection cycle
Population: The FAS was the subset of participants in the SES for whom at least a baseline value (Day 1 of the first cycle, Visit 2) of AS score of PF was available. For participants from lead-in study at least one post-baseline value was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of Left and Right PF at Day 29 (Week 4) of Each Injection Cycle | Left PF Day 29 of 1st Injection Cycle | 1.7 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of Left and Right PF at Day 29 (Week 4) of Each Injection Cycle | Left PF Day 29 of 2nd Injection Cycle | 1.8 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of Left and Right PF at Day 29 (Week 4) of Each Injection Cycle | Left PF Day 29 of 3rd Injection Cycle | 1.9 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of Left and Right PF at Day 29 (Week 4) of Each Injection Cycle | Left PF Day 29 of 4th Injection Cycle | 2 units on a scale | Standard Deviation 0.9 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of Left and Right PF at Day 29 (Week 4) of Each Injection Cycle | Right PF Day 29 of 1st Injection Cycle | 1.7 units on a scale | Standard Deviation 0.7 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of Left and Right PF at Day 29 (Week 4) of Each Injection Cycle | Right PF Day 29 of 2nd Injection Cycle | 1.8 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of Left and Right PF at Day 29 (Week 4) of Each Injection Cycle | Right PF Day 29 of 3rd Injection Cycle | 1.9 units on a scale | Standard Deviation 0.8 |
| 16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin) | Investigator's Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) of Left and Right PF at Day 29 (Week 4) of Each Injection Cycle | Right PF Day 29 of 4th Injection Cycle | 2 units on a scale | Standard Deviation 0.9 |