Trial Outcomes & Findings for Long-term Open-label Study of Botulinumtoxin Type A to Treat Spasticity of Leg(s) or Leg(s) and Arm in Cerebral Palsy (NCT NCT01905683)
NCT ID: NCT01905683
Last Updated: 2017-10-27
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
370 participants
Primary outcome timeframe
From the timepoint of first injection up to end of study visit (Week 50-66)
Results posted on
2017-10-27
Participant Flow
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.
Participant milestones
| Measure |
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 gross motor function classification system expanded and revised (GMFCS-E\&R) levels I to III.
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|---|---|
|
Overall Study
STARTED
|
370
|
|
Overall Study
COMPLETED
|
319
|
|
Overall Study
NOT COMPLETED
|
51
|
Reasons for withdrawal
| Measure |
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 gross motor function classification system expanded and revised (GMFCS-E\&R) levels I to III.
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|---|---|
|
Overall Study
Protocol Violation
|
1
|
|
Overall Study
Re-injection criteria not met; others
|
13
|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Lack of Efficacy
|
8
|
|
Overall Study
Withdrawal by Subject
|
20
|
|
Overall Study
Adverse Event
|
4
|
|
Overall Study
Lost to Follow-up
|
4
|
Baseline Characteristics
Long-term Open-label Study of Botulinumtoxin Type A to Treat Spasticity of Leg(s) or Leg(s) and Arm in Cerebral Palsy
Baseline characteristics by cohort
| Measure |
16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=370 Participants
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.
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|---|---|
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Age, Continuous
|
6.2 years
STANDARD_DEVIATION 4.1 • n=5 Participants
|
|
Age, Customized
Children (2-11 years)
|
317 Participants
n=5 Participants
|
|
Age, Customized
Adolescents (12-17 years)
|
53 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
150 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
220 Participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
1 participants
n=5 Participants
|
|
Region of Enrollment
South Korea
|
59 participants
n=5 Participants
|
|
Region of Enrollment
Romania
|
22 participants
n=5 Participants
|
|
Region of Enrollment
Turkey
|
5 participants
n=5 Participants
|
|
Region of Enrollment
Czechia
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Ukraine
|
170 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
67 participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Slovakia
|
5 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Estonia
|
5 participants
n=5 Participants
|
|
Region of Enrollment
Russia
|
33 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=370 Participants
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.
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|---|---|
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Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
1st Injection Cycle
|
53 participants
|
|
Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
2nd Injection Cycle
|
44 participants
|
|
Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
3rd Injection Cycle
|
26 participants
|
|
Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
4th Injection Cycle
|
31 participants
|
|
Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
Overall Period
|
109 participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=370 Participants
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.
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|---|---|
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Occurrence of Treatment Emergent Adverse Events of Special Interest (TEAESI) Overall and Per Injection Cycle
1st Injection Cycle
|
1 participants
|
|
Occurrence of Treatment Emergent Adverse Events of Special Interest (TEAESI) Overall and Per Injection Cycle
2nd Injection Cycle
|
2 participants
|
|
Occurrence of Treatment Emergent Adverse Events of Special Interest (TEAESI) Overall and Per Injection Cycle
3rd Injection Cycle
|
1 participants
|
|
Occurrence of Treatment Emergent Adverse Events of Special Interest (TEAESI) Overall and Per Injection Cycle
4th Injection Cycle
|
0 participants
|
|
Occurrence of Treatment Emergent Adverse Events of Special Interest (TEAESI) Overall and Per Injection Cycle
Overall Period
|
3 participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=370 Participants
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.
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|---|---|
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Occurrence of Treatment-emergent Serious Adverse Events (TESAEs) Overall and Per Injection Cycle
1st Injection Cycle
|
6 participants
|
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Occurrence of Treatment-emergent Serious Adverse Events (TESAEs) Overall and Per Injection Cycle
2nd Injection Cycle
|
5 participants
|
|
Occurrence of Treatment-emergent Serious Adverse Events (TESAEs) Overall and Per Injection Cycle
3rd Injection Cycle
|
5 participants
|
|
Occurrence of Treatment-emergent Serious Adverse Events (TESAEs) Overall and Per Injection Cycle
4th Injection Cycle
|
1 participants
|
|
Occurrence of Treatment-emergent Serious Adverse Events (TESAEs) Overall and Per Injection Cycle
Overall Period
|
16 participants
|
SECONDARY outcome
Timeframe: Day 99 (Week 14) of 1st, 2nd, 3rd and 4th injection cyclePopulation: The SES was the subset of all participants treated with IP at least once.
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.
Outcome measures
| Measure |
16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=370 Participants
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.
|
|---|---|
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Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
1st Injection Cycle: Very Good
|
203 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
1st Injection Cycle: Good
|
119 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
1st Injection Cycle: Moderate
|
23 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
1st Injection Cycle: Poor
|
5 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
2nd Injection Cycle: Very Good
|
225 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
2nd Injection Cycle: Good
|
87 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
2nd Injection Cycle: Moderate
|
24 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
2nd Injection Cycle: Poor
|
4 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
3rd Injection Cycle: Very Good
|
223 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
3rd Injection Cycle: Good
|
74 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
3rd Injection Cycle: Moderate
|
17 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
3rd Injection Cycle: Poor
|
9 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
4th Injection Cycle: Very Good
|
241 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
4th Injection Cycle: Good
|
76 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
4th Injection Cycle: Moderate
|
16 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
4th Injection Cycle: Poor
|
8 participants
|
|
Investigator's Global Assessment of Tolerability at Day 99 (Week 14) of Each Injection Cycle
4th Injection Cycle: Not assessed
|
29 participants
|
SECONDARY outcome
Timeframe: 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 CyclePopulation: 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.
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.
Outcome measures
| Measure |
16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=370 Participants
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.
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|---|---|
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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
|
|
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
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|
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
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|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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 outcome
Timeframe: Day 29 (Week 4) of 1st, 2nd, 3rd and 4th injection cyclePopulation: 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.
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).
Outcome measures
| Measure |
16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=370 Participants
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.
|
|---|---|
|
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
|
|
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
|
|
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
|
|
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
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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
|
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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
|
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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
|
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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
|
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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
|
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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
|
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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
|
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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 outcome
Timeframe: Day 29 (Week 4) of 1st, 2nd, 3rd and 4th injection cyclePopulation: 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.
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.
Outcome measures
| Measure |
16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=370 Participants
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.
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|---|---|
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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
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1.7 units on a scale
Standard Deviation 0.7
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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
|
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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
|
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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
|
|
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
|
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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
|
|
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
|
|
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
|
SECONDARY outcome
Timeframe: 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 ICPopulation: 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.
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.
Outcome measures
| Measure |
16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=370 Participants
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.
|
|---|---|
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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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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 outcome
Timeframe: 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 ICPopulation: 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.
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.
Outcome measures
| Measure |
16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=370 Participants
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.
|
|---|---|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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 outcome
Timeframe: 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.
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).
Outcome measures
| Measure |
16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=370 Participants
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.
|
|---|---|
|
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
|
|
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
|
|
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
|
|
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
|
Adverse Events
16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
Serious events: 16 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=370 participants at risk
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.
|
|---|---|
|
Surgical and medical procedures
Tenotomy
|
0.54%
2/370 • Number of events 3 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Surgical and medical procedures
Cast application
|
0.27%
1/370 • Number of events 1 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Cardiac disorders
Arrhythmia
|
0.27%
1/370 • Number of events 1 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Nervous system disorders
Epilepsy
|
0.54%
2/370 • Number of events 2 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Nervous system disorders
Clonic convulsion
|
0.27%
1/370 • Number of events 1 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Nervous system disorders
Febrile convulsion
|
0.27%
1/370 • Number of events 1 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Nervous system disorders
Seizure
|
0.27%
1/370 • Number of events 4 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Gastrointestinal disorders
Gastritis
|
0.27%
1/370 • Number of events 1 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Infections and infestations
Gastroenteritis
|
0.81%
3/370 • Number of events 4 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Infections and infestations
Bronchitis
|
0.54%
2/370 • Number of events 3 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Infections and infestations
Adenoiditis
|
0.27%
1/370 • Number of events 1 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Infections and infestations
Adenovirus infection
|
0.27%
1/370 • Number of events 2 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Infections and infestations
Croup infectious
|
0.27%
1/370 • Number of events 1 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Infections and infestations
Nasopharyngitis
|
0.27%
1/370 • Number of events 1 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Infections and infestations
Enteritis infectious
|
0.27%
1/370 • Number of events 1 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Infections and infestations
Respiratory tract infection viral
|
0.27%
1/370 • Number of events 1 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Infections and infestations
Hemagglutinin Type 1 and Neuraminidase Type 1 (H1N1) influenza
|
0.27%
1/370 • Number of events 1 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
|
Infections and infestations
Pneumonia
|
0.27%
1/370 • Number of events 1 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
Other adverse events
| Measure |
16 - 20 U/kg Body Weight IncobotulinumtoxinA (Xeomin)
n=370 participants at risk
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.
|
|---|---|
|
Infections and infestations
Nasopharyngitis
|
5.4%
20/370 • Number of events 34 • From the time point of first injection up to end of study visit (Week 50-66)
Adverse Events were collected systematically at each visit by the investigator.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Publication of study information usually requires agreement with the sponsor. In case of justified doubts by the sponsor, the INVESTIGATOR will consider these doubts in the publication as long as the scientific neutrality is not affected.
- Publication restrictions are in place
Restriction type: OTHER