Trial Outcomes & Findings for Dose-response Study of Efficacy and Safety of Botulinum Toxin Type A to Treat Spasticity of the Arm(s) or of Arm(s) and Leg(s) in Cerebral Palsy (NCT NCT02002884)
NCT ID: NCT02002884
Last Updated: 2021-08-05
Results Overview
The AS categorizes severity of spasticity by judging resistance to passive movement. Spasticity was assessed by using the 5-point AS with:0 (no increase in tone); 1 (slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2 (more marked increase in tone, but limb easily flexed); 3 (considerable increase in tone -passive movements difficult); 4 (limb rigid in flexion or extension). Values represent least square (LS) mean differences between baseline and Week 4 resulting from Mixed Model Repeated Measurement (MMRM) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
351 participants
Primary outcome timeframe
Baseline and Week 4
Results posted on
2021-08-05
Participant Flow
The study was conducted at 28 investigative sites in Mexico, Argentina, Russian federation, Ukraine, United States and Poland.
A total of 372 participants were screened, 351 participants were randomized and 350 participants were randomized and treated in the study. 331 participants completed the main period (MP) and moved to the open-label-extension period (OLEX) out of which 281 participants completed the OLEX period.
Participant milestones
| Measure |
MP Low Dose Group
Participants in low dose group received intramuscular injections of 2 Units per kilogram (U/kg) NT 201 (maximum of 50 Units \[U\] in participants with greater than \[\>\] 25 kilogram \[kg\] body weight \[BW\]) into spastic muscles of one of the upper Limb (UL) on Day 1 of MP. If the contralateral UL or one or both lower limb (LL) were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's Gross Motor Function Classification System (GMFCS) level.
|
MP Mid Dose Group
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
Main Period (MP)
STARTED
|
87
|
88
|
176
|
0
|
|
Main Period (MP)
Treated
|
87
|
87
|
176
|
0
|
|
Main Period (MP)
COMPLETED
|
81
|
82
|
168
|
0
|
|
Main Period (MP)
NOT COMPLETED
|
6
|
6
|
8
|
0
|
|
Open-Label Extension Period (OLEX)
STARTED
|
0
|
0
|
0
|
331
|
|
Open-Label Extension Period (OLEX)
COMPLETED
|
0
|
0
|
0
|
281
|
|
Open-Label Extension Period (OLEX)
NOT COMPLETED
|
0
|
0
|
0
|
50
|
Reasons for withdrawal
| Measure |
MP Low Dose Group
Participants in low dose group received intramuscular injections of 2 Units per kilogram (U/kg) NT 201 (maximum of 50 Units \[U\] in participants with greater than \[\>\] 25 kilogram \[kg\] body weight \[BW\]) into spastic muscles of one of the upper Limb (UL) on Day 1 of MP. If the contralateral UL or one or both lower limb (LL) were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's Gross Motor Function Classification System (GMFCS) level.
|
MP Mid Dose Group
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
Main Period (MP)
Other
|
0
|
3
|
3
|
0
|
|
Main Period (MP)
Adverse Event
|
0
|
1
|
1
|
0
|
|
Main Period (MP)
Withdrawal by Subject
|
6
|
2
|
2
|
0
|
|
Main Period (MP)
Lost to Follow-up
|
0
|
0
|
2
|
0
|
|
Open-Label Extension Period (OLEX)
Other
|
0
|
0
|
0
|
24
|
|
Open-Label Extension Period (OLEX)
Physician Decision
|
0
|
0
|
0
|
1
|
|
Open-Label Extension Period (OLEX)
Adverse Event
|
0
|
0
|
0
|
5
|
|
Open-Label Extension Period (OLEX)
Withdrawal by Subject
|
0
|
0
|
0
|
10
|
|
Open-Label Extension Period (OLEX)
Lost to Follow-up
|
0
|
0
|
0
|
10
|
Baseline Characteristics
Dose-response Study of Efficacy and Safety of Botulinum Toxin Type A to Treat Spasticity of the Arm(s) or of Arm(s) and Leg(s) in Cerebral Palsy
Baseline characteristics by cohort
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=88 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
Total
n=351 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
7.2 Years
STANDARD_DEVIATION 4.70 • n=5 Participants
|
7.4 Years
STANDARD_DEVIATION 4.13 • n=7 Participants
|
7.3 Years
STANDARD_DEVIATION 4.40 • n=5 Participants
|
7.3 Years
STANDARD_DEVIATION 4.40 • n=4 Participants
|
|
Sex: Female, Male
Female
|
38 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
131 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
49 Participants
n=5 Participants
|
57 Participants
n=7 Participants
|
114 Participants
n=5 Participants
|
220 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
16 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
87 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
71 Participants
n=5 Participants
|
62 Participants
n=7 Participants
|
131 Participants
n=5 Participants
|
264 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
81 Participants
n=5 Participants
|
75 Participants
n=7 Participants
|
160 Participants
n=5 Participants
|
316 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
3 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
28 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 4Population: The full analysis set (FAS) was the subset in the safety evaluation set (SES) of the MP for whom the primary efficacy variable or co-primary efficacy variable were available. Number of participants who were evaluable for this measure at a given time period and were included in the assessment.
The AS categorizes severity of spasticity by judging resistance to passive movement. Spasticity was assessed by using the 5-point AS with:0 (no increase in tone); 1 (slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2 (more marked increase in tone, but limb easily flexed); 3 (considerable increase in tone -passive movements difficult); 4 (limb rigid in flexion or extension). Values represent least square (LS) mean differences between baseline and Week 4 resulting from Mixed Model Repeated Measurement (MMRM) models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Outcome measures
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
MP: Change From Baseline in Ashworth Scale (AS) in UL Primary Clinical Target Pattern at Week 4
High versus low
|
-0.93 Unit on a scale
Standard Error 0.078
|
—
|
-1.15 Unit on a scale
Standard Error 0.056
|
—
|
|
MP: Change From Baseline in Ashworth Scale (AS) in UL Primary Clinical Target Pattern at Week 4
Mid versus low
|
-0.96 Unit on a scale
Standard Error 0.082
|
-1.02 Unit on a scale
Standard Error 0.082
|
—
|
—
|
PRIMARY outcome
Timeframe: Week 4Population: The FAS was the subset in the SES of the MP for whom the primary efficacy variable or co-primary efficacy variable were available (that is, all participants who had at least an AS score in clinical pattern flexed elbow or flexed wrist at baseline \[Day 1\] or Investigator's GICS at Day 29 \[Week 4\]).
The GICS was used to measure independently the investigator's impression of change due to treatment. The response option was a common 7-point Likert scale, that ranges from +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse). Values represent LS mean differences between baseline and Week 4 resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Outcome measures
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
Co-primary Variable MP: Investigator's Global Impression of Change Scale (GICS) at Week 4
High versus low
|
1.55 Unit on a scale
Standard Error 0.083
|
—
|
1.64 Unit on a scale
Standard Error 0.062
|
—
|
|
Co-primary Variable MP: Investigator's Global Impression of Change Scale (GICS) at Week 4
Mid versus low
|
1.57 Unit on a scale
Standard Error 0.089
|
1.44 Unit on a scale
Standard Error 0.092
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 4Population: The FAS was the subset in the SES of the MP for whom the primary efficacy variable or co-primary efficacy variable were available. Number of participants who were evaluable for this measure at a given time period and were included in the assessment.
The AS categorizes the severity of spasticity by judging resistance to passive movement. Spasticity was assessed by 5-point scale at visits, where: 0 (no increase in tone); 1(slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2(more marked increase in tone, but limb easily flexed); 3(considerable increase in tone - passive movements difficult); 4(limb rigid in flexion or extension). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Outcome measures
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
MP: Change From Baseline in AS Score of the Other Treated UL Main Clinical Target Pattern at Week 4
High versus low
|
-1.03 Unit on a scale
Standard Error 0.083
|
—
|
-1.13 Unit on a scale
Standard Error 0.061
|
—
|
|
MP: Change From Baseline in AS Score of the Other Treated UL Main Clinical Target Pattern at Week 4
Mid versus low
|
-1.08 Unit on a scale
Standard Error 0.087
|
-1.22 Unit on a scale
Standard Error 0.090
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 4Population: The FAS was the subset in the SES of the MP for whom the primary efficacy variable or co-primary efficacy variable were available. Number of participants who were evaluable for this measure at a given time period and were included in the assessment.
The AS categorizes the severity of spasticity by judging resistance to passive movement. Spasticity was assessed by 5-point scale at visits, where: 0 (no increase in tone); 1(slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2(more marked increase in tone, but limb easily flexed); 3(considerable increase in tone - passive movements difficult); 4(limb rigid in flexion or extension). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Outcome measures
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
MP: Change From Baseline in AS Score in UL Treated Clenched Fist With Flexed Wrist at Week 4
High versus low
|
-0.53 Unit on a scale
Standard Error 0.212
|
—
|
-1.00 Unit on a scale
Standard Error 0.133
|
—
|
|
MP: Change From Baseline in AS Score in UL Treated Clenched Fist With Flexed Wrist at Week 4
Mid versus low
|
-0.070 Unit on a scale
Standard Error 0.202
|
-1.04 Unit on a scale
Standard Error 0.176
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 4Population: The FAS was the subset in the SES of the MP for whom the primary efficacy variable or co-primary efficacy variable were available. Number of participants who were evaluable for this measure at a given time period and were included in the assessment.
The AS categorizes the severity of spasticity by judging resistance to passive movement. Spasticity was assessed by 5-point scale at visits, where: 0 (no increase in tone); 1(slight increase in tone giving a "catch" when the limb was moved in flexion or extension); 2(more marked increase in tone, but limb easily flexed); 3(considerable increase in tone - passive movements difficult); 4(limb rigid in flexion or extension). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Outcome measures
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4
Flexed elbow: High versus Low
|
-0.99 Unit on a scale
Standard Error 0.076
|
—
|
-1.18 Unit on a scale
Standard Error 0.056
|
—
|
|
MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4
Flexed elbow: Mid versus Low
|
-1.01 Unit on a scale
Standard Error 0.081
|
-1.17 Unit on a scale
Standard Error 0.082
|
—
|
—
|
|
MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4
Flexed wrist: High versus Low
|
-0.96 Unit on a scale
Standard Error 0.085
|
—
|
-1.08 Unit on a scale
Standard Error 0.061
|
—
|
|
MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4
Flexed wrist: Mid versus Low
|
-1.01 Unit on a scale
Standard Error 0.087
|
-1.05 Unit on a scale
Standard Error 0.087
|
—
|
—
|
|
MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4
Clenched fist: High versus Low
|
-0.64 Unit on a scale
Standard Error 0.136
|
—
|
-1.09 Unit on a scale
Standard Error 0.096
|
—
|
|
MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4
Clenched fist: Mid versus Low
|
-0.58 Unit on a scale
Standard Error 0.145
|
-0.87 Unit on a scale
Standard Error 0.141
|
—
|
—
|
|
MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4
Thumb in palm: High versus Low
|
-0.88 Unit on a scale
Standard Error 0.116
|
—
|
-1.11 Unit on a scale
Standard Error 0.083
|
—
|
|
MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4
Thumb in palm: Mid versus Low
|
-0.93 Unit on a scale
Standard Error 0.131
|
-1.14 Unit on a scale
Standard Error 0.123
|
—
|
—
|
|
MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4
Pronated forearm: High versus Low
|
-0.88 Unit on a scale
Standard Error 0.080
|
—
|
-1.02 Unit on a scale
Standard Error 0.058
|
—
|
|
MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4
Pronated forearm: Mid versus Low
|
-0.87 Unit on a scale
Standard Error 0.086
|
-0.94 Unit on a scale
Standard Error 0.088
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, and 14Population: The FAS was the subset in the SES of the MP for whom the primary efficacy variable or co-primary efficacy variable were available. Number of participants who were evaluable for this measure at a given time period and were included in the assessment.
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). Values represent LS mean differences between baseline and Week 4 resulting from MMRM models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison. P/C = Parent/Caregiver.
Outcome measures
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
UL, Participant, Week 4 High versus low
|
-0.42 Unit on a scale
Standard Error 0.217
|
—
|
-0.75 Unit on a scale
Standard Error 0.199
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
UL, Participant, Week 4 Mid versus low
|
-0.39 Unit on a scale
Standard Error 0.256
|
-0.67 Unit on a scale
Standard Error 0.289
|
—
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
UL, Participant, Week 8 High versus low
|
-0.52 Unit on a scale
Standard Error 0.206
|
—
|
-0.64 Unit on a scale
Standard Error 0.188
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
UL, Participant, Week 8 Mid versus low
|
-0.63 Unit on a scale
Standard Error 0.259
|
-0.55 Unit on a scale
Standard Error 0.290
|
—
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
UL, P/C, Week 14 Mid versus Low
|
-0.31 Unit on a scale
Standard Error 0.100
|
-0.25 Unit on a scale
Standard Error 0.107
|
—
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
UL, Participant, Week 14 High versus low
|
-0.56 Unit on a scale
Standard Error 0.217
|
—
|
-0.59 Unit on a scale
Standard Error 0.202
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
UL, Participant, Week 14 Mid versus low
|
-0.66 Unit on a scale
Standard Error 0.327
|
-0.59 Unit on a scale
Standard Error 0.361
|
—
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
UL, P/C, Week 4 High versus low
|
-0.46 Unit on a scale
Standard Error 0.102
|
—
|
-0.44 Unit on a scale
Standard Error 0.076
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
UL, P/C, Week 4 Mid versus low
|
-0.43 Unit on a scale
Standard Error 0.106
|
-0.28 Unit on a scale
Standard Error 0.115
|
—
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
UL, P/C, Week 8 High versus low
|
-0.40 Unit on a scale
Standard Error 0.095
|
—
|
-0.44 Unit on a scale
Standard Error 0.070
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
UL, P/C, Week 8 Mid versus low
|
-0.43 Unit on a scale
Standard Error 0.100
|
-0.34 Unit on a scale
Standard Error 0.109
|
—
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
UL, P/C, Week 14 High versus Low
|
-0.23 Unit on a scale
Standard Error 0.105
|
—
|
-0.24 Unit on a scale
Standard Error 0.071
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
LL, Participant, Week 4 High versus Low
|
-0.74 Unit on a scale
Standard Error 0.282
|
—
|
-0.62 Unit on a scale
Standard Error 0.250
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
LL, Participant, Week 4 Mid versus Low
|
-0.46 Unit on a scale
Standard Error 0.305
|
-0.55 Unit on a scale
Standard Error 0.321
|
—
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
LL, Participant, Week 8 High versus Low
|
-1.04 Unit on a scale
Standard Error 0.241
|
—
|
-0.69 Unit on a scale
Standard Error 0.218
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
LL, Participant, Week 8 Mid versus Low
|
-0.90 Unit on a scale
Standard Error 0.261
|
-0.81 Unit on a scale
Standard Error 0.284
|
—
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
LL, Participant, Week 14 High versus Low
|
-0.71 Unit on a scale
Standard Error 0.275
|
—
|
-0.57 Unit on a scale
Standard Error 0.245
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
LL, Participant, Week 14 Mid versus Low
|
-0.67 Unit on a scale
Standard Error 0.315
|
-0.63 Unit on a scale
Standard Error 0.335
|
—
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
LL, P/C, Week 4 High versus Low
|
-0.50 Unit on a scale
Standard Error 0.105
|
—
|
-0.52 Unit on a scale
Standard Error 0.077
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
LL, P/C, Week 4 Mid versus Low
|
-0.46 Unit on a scale
Standard Error 0.103
|
-0.42 Unit on a scale
Standard Error 0.111
|
—
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
LL, P/C, Week 8 High versus Low
|
-0.56 Unit on a scale
Standard Error 0.098
|
—
|
-0.51 Unit on a scale
Standard Error 0.074
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
LL, P/C, Week 8 Mid versus Low
|
-0.52 Unit on a scale
Standard Error 0.102
|
-0.36 Unit on a scale
Standard Error 0.111
|
—
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
LL, P/C, Week 14 High versus Low
|
-0.33 Unit on a scale
Standard Error 0.108
|
—
|
-0.32 Unit on a scale
Standard Error 0.078
|
—
|
|
MP: Change From Baseline in Scores of Pain Intensity (From Participants) and Pain Frequency (From Parent/Caregiver) Assessed With 'Questionnaire on Pain Caused by Spasticity (QPS)'
LL, P/C, Week 14 Mid versus Low
|
-0.37 Unit on a scale
Standard Error 0.086
|
-0.31 Unit on a scale
Standard Error 0.090
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 4Population: The FAS was the subset in the SES of the MP for whom the primary efficacy variable or co-primary efficacy variable were available. Number of participants who were evaluable for this measure at a given time period and were included in the assessment.
The GICS was used to measure independently the child's/adolescent's, and parent's or caregiver's impression of change due to treatment. The response option was a common 7-point Likert scale, that ranges from: +3(very much improved); +2(much improved); +1(minimally improved); 0(no change); -1(minimally worse); -2(much worse); -3(very much worse). Values represent LS mean differences between baseline and Week 4 resulting from ANCOVA models comparing high versus low and in a second step mid versus low dose groups, respectively. Values for the low group may differ slightly depending on the comparison and are therefore provided separately for each comparison.
Outcome measures
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
MP: Child's/Adolescent's, and Parent's/Caregiver's GICS in UL at Week 4
Participant: High versus Low
|
1.51 Unit on a scale
Standard Error 0.153
|
—
|
1.63 Unit on a scale
Standard Error 0.139
|
—
|
|
MP: Child's/Adolescent's, and Parent's/Caregiver's GICS in UL at Week 4
Participant: Mid versus Low
|
1.53 Unit on a scale
Standard Error 0.180
|
1.48 Unit on a scale
Standard Error 0.190
|
—
|
—
|
|
MP: Child's/Adolescent's, and Parent's/Caregiver's GICS in UL at Week 4
Parent/Caregiver: High versus Low
|
1.41 Unit on a scale
Standard Error 0.087
|
—
|
1.60 Unit on a scale
Standard Error 0.065
|
—
|
|
MP: Child's/Adolescent's, and Parent's/Caregiver's GICS in UL at Week 4
Parent/Caregiver: Mid versus Low
|
1.36 Unit on a scale
Standard Error 0.094
|
1.29 Unit on a scale
Standard Error 0.097
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 66Population: The SES was the subset of all participants treated in the MP and OLEX with study medication at least once. Number of participants who were evaluable for this measure at a given time period and were included in the assessment.
Outcome measures
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
n=331 Participants
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
Number of Participants With Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Treatment Cycle
Overall
|
21 Participants
|
13 Participants
|
42 Participants
|
114 Participants
|
|
Number of Participants With Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Treatment Cycle
First injection cycle (MP)
|
21 Participants
|
13 Participants
|
42 Participants
|
—
|
|
Number of Participants With Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Treatment Cycle
Second injection cycle (OLEX)
|
—
|
—
|
—
|
64 Participants
|
|
Number of Participants With Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Treatment Cycle
Third injection cycle (OLEX)
|
—
|
—
|
—
|
42 Participants
|
|
Number of Participants With Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Treatment Cycle
Fourth injection cycle (OLEX)
|
—
|
—
|
—
|
48 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 66Population: The SES was the subset of all participants treated in the MP and OLEX with study medication at least once. Number of participants who were evaluable for this measure at a given time period and were included in the assessment.
Outcome measures
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
n=331 Participants
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
Number of Participants With Occurrence of TEAEs of Special Interest (TEAESIs) Overall and Per Treatment Cycle
Overall
|
1 Participants
|
1 Participants
|
1 Participants
|
5 Participants
|
|
Number of Participants With Occurrence of TEAEs of Special Interest (TEAESIs) Overall and Per Treatment Cycle
First injection cycle (MP)
|
1 Participants
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants With Occurrence of TEAEs of Special Interest (TEAESIs) Overall and Per Treatment Cycle
Second injection cycle (OLEX)
|
—
|
—
|
—
|
2 Participants
|
|
Number of Participants With Occurrence of TEAEs of Special Interest (TEAESIs) Overall and Per Treatment Cycle
Third injection cycle (OLEX)
|
—
|
—
|
—
|
3 Participants
|
|
Number of Participants With Occurrence of TEAEs of Special Interest (TEAESIs) Overall and Per Treatment Cycle
Fourth injection cycle (OLEX)
|
—
|
—
|
—
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 66Population: The SES were the subset of all participants treated in the MP and OLEX with study medication at least once. Number of participants who were evaluable for this measure at a given time period and were included in the assessment.
Outcome measures
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
n=331 Participants
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
Number of Participants With Occurrence of Serious TEAEs (TESAEs) Overall and Per Treatment Cycle
Overall
|
2 Participants
|
1 Participants
|
2 Participants
|
16 Participants
|
|
Number of Participants With Occurrence of Serious TEAEs (TESAEs) Overall and Per Treatment Cycle
First injection cycle (MP)
|
2 Participants
|
1 Participants
|
2 Participants
|
—
|
|
Number of Participants With Occurrence of Serious TEAEs (TESAEs) Overall and Per Treatment Cycle
Second injection cycle (OLEX)
|
—
|
—
|
—
|
7 Participants
|
|
Number of Participants With Occurrence of Serious TEAEs (TESAEs) Overall and Per Treatment Cycle
Third injection cycle (OLEX)
|
—
|
—
|
—
|
9 Participants
|
|
Number of Participants With Occurrence of Serious TEAEs (TESAEs) Overall and Per Treatment Cycle
Fourth injection cycle (OLEX)
|
—
|
—
|
—
|
3 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 66Population: The SES was the subset of all participants treated in MP and OLEX with study medication at least once. Number of participants who were evaluable for this measure at a given time period and were included in the assessment.
Outcome measures
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
n=331 Participants
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
Number of Participants With Occurrence of TEAEs Related to Treatment Overall and Per Treatment Cycle
Overall
|
0 Participants
|
0 Participants
|
3 Participants
|
5 Participants
|
|
Number of Participants With Occurrence of TEAEs Related to Treatment Overall and Per Treatment Cycle
First injection cycle (MP)
|
0 Participants
|
0 Participants
|
3 Participants
|
—
|
|
Number of Participants With Occurrence of TEAEs Related to Treatment Overall and Per Treatment Cycle
Second injection cycle (OLEX)
|
—
|
—
|
—
|
2 Participants
|
|
Number of Participants With Occurrence of TEAEs Related to Treatment Overall and Per Treatment Cycle
Third injection cycle (OLEX)
|
—
|
—
|
—
|
2 Participants
|
|
Number of Participants With Occurrence of TEAEs Related to Treatment Overall and Per Treatment Cycle
Fourth injection cycle (OLEX)
|
—
|
—
|
—
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 66Population: The SES was the subset of all participants treated in the MP and OLEX with study medication at least once. Number of participants who were evaluable for this measure at a given time period and were included in the assessment.
Outcome measures
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
n=331 Participants
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Overall: Mild
|
15 Participants
|
10 Participants
|
33 Participants
|
62 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Overall: Moderate
|
6 Participants
|
2 Participants
|
7 Participants
|
44 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Overall: Severe
|
0 Participants
|
1 Participants
|
2 Participants
|
8 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
First injection cycle (MP): Mild
|
15 Participants
|
10 Participants
|
33 Participants
|
—
|
|
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
First injection cycle (MP): Moderate
|
6 Participants
|
2 Participants
|
7 Participants
|
—
|
|
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
First injection cycle (MP): Severe
|
0 Participants
|
1 Participants
|
2 Participants
|
—
|
|
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Second injection cycle (OLEX): Mild
|
—
|
—
|
—
|
43 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Second injection cycle (OLEX): Moderate
|
—
|
—
|
—
|
18 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Second injection cycle (OLEX): Severe
|
—
|
—
|
—
|
3 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Third injection cycle (OLEX): Mild
|
—
|
—
|
—
|
23 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Third injection cycle (OLEX): Moderate
|
—
|
—
|
—
|
15 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Third injection cycle (OLEX): Severe
|
—
|
—
|
—
|
4 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Fourth injection cycle (OLEX): Mild
|
—
|
—
|
—
|
28 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Fourth injection cycle (OLEX): Moderate
|
—
|
—
|
—
|
19 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle
Fourth injection cycle (OLEX): Severe
|
—
|
—
|
—
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 66Population: The SES were the subset of all participants treated in the MP and OLEX with study medication at least once. Number of participants who were evaluable for this measure at a given time period and were included in the assessment.
Outcome measures
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
n=331 Participants
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle
Overall: Related
|
0 Participants
|
0 Participants
|
3 Participants
|
5 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle
Overall: Not related
|
21 Participants
|
13 Participants
|
39 Participants
|
109 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle
First injection cycle (MP): Related
|
0 Participants
|
0 Participants
|
3 Participants
|
—
|
|
Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle
First injection cycle (MP): Not related
|
21 Participants
|
13 Participants
|
39 Participants
|
—
|
|
Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle
Second injection cycle (OLEX): Related
|
—
|
—
|
—
|
2 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle
Second injection cycle (OLEX): Not related
|
—
|
—
|
—
|
62 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle
Third injection cycle (OLEX): Related
|
—
|
—
|
—
|
2 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle
Third injection cycle (OLEX): Not related
|
—
|
—
|
—
|
40 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle
Fourth injection cycle (OLEX): Related
|
—
|
—
|
—
|
1 Participants
|
|
Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle
Fourth injection cycle (OLEX): Not related
|
—
|
—
|
—
|
47 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 66Population: The SES were the subset of all participants treated in the MP and OLEX with study medication at least once. Number of participants who were evaluable for this measure at a given time period and were included in the assessment.
Outcome measures
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
n=331 Participants
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Overall: Resolved
|
18 Participants
|
10 Participants
|
39 Participants
|
96 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Overall: Resolved with sequelae
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Overall: Resolving
|
0 Participants
|
2 Participants
|
1 Participants
|
7 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Overall: Not resolved
|
2 Participants
|
1 Participants
|
1 Participants
|
8 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Overall: Unknown
|
0 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Overall: Fatal
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
First injection cycle (MP): Resolved
|
18 Participants
|
10 Participants
|
39 Participants
|
—
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
First injection cycle (MP): Resolved with sequelae
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
First injection cycle (MP): Resolving
|
0 Participants
|
2 Participants
|
1 Participants
|
—
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
First injection cycle (MP): Not resolved
|
2 Participants
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
First injection cycle (MP): Unknown
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
First injection cycle (MP): Fatal
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Second injection cycle (OLEX): Resolved
|
—
|
—
|
—
|
57 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Secondinjection cycle(OLEX):Resolved with sequelae
|
—
|
—
|
—
|
0 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Second injection cycle (OLEX): Resolving
|
—
|
—
|
—
|
3 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Second injection cycle (OLEX): Not resolved
|
—
|
—
|
—
|
4 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Second injection cycle (OLEX): Unknown
|
—
|
—
|
—
|
0 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Second injection cycle (OLEX): Fatal
|
—
|
—
|
—
|
0 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Third injection cycle (OLEX): Resolved
|
—
|
—
|
—
|
37 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Third injection cycle(OLEX):Resolved with sequelae
|
—
|
—
|
—
|
0 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Third injection cycle (OLEX): Resolving
|
—
|
—
|
—
|
0 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Third injection cycle (OLEX): Not resolved
|
—
|
—
|
—
|
4 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Third injection cycle (OLEX): Unknown
|
—
|
—
|
—
|
1 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Third injection cycle (OLEX): Fatal
|
—
|
—
|
—
|
0 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Fourth injection cycle (OLEX): Resolved
|
—
|
—
|
—
|
39 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Fourthinjection cycle(OLEX):Resolved with sequelae
|
—
|
—
|
—
|
1 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Fourth injection cycle (OLEX): Resolving
|
—
|
—
|
—
|
4 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Fourth injection cycle (OLEX): Not resolved
|
—
|
—
|
—
|
2 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Fourth injection cycle (OLEX): Unknown
|
—
|
—
|
—
|
2 Participants
|
|
Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle
Fourth injection cycle (OLEX): Fatal
|
—
|
—
|
—
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 66Population: The SES was the subset of all participants treated in the MP and OLEX with study medication at least once. Number of participants who were evaluable for this measure at a given time period and were included in the assessment.
Outcome measures
| Measure |
MP Low Dose Group
n=87 Participants
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 Participants
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 Participants
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
n=331 Participants
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
Number of Participants With Occurrence of TEAEs Leading to Discontinuation Overall and Per Treatment Cycle
Third injection cycle (OLEX)
|
—
|
—
|
—
|
2 Participants
|
|
Number of Participants With Occurrence of TEAEs Leading to Discontinuation Overall and Per Treatment Cycle
Overall
|
0 Participants
|
1 Participants
|
1 Participants
|
5 Participants
|
|
Number of Participants With Occurrence of TEAEs Leading to Discontinuation Overall and Per Treatment Cycle
First injection cycle (MP)
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
|
Number of Participants With Occurrence of TEAEs Leading to Discontinuation Overall and Per Treatment Cycle
Second injection cycle (OLEX)
|
—
|
—
|
—
|
3 Participants
|
|
Number of Participants With Occurrence of TEAEs Leading to Discontinuation Overall and Per Treatment Cycle
Fourth injection cycle (OLEX)
|
—
|
—
|
—
|
0 Participants
|
Adverse Events
MP Low Dose Group
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
MP Mid Dose Group
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
MP High Dose Group
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
OLEX (3 Injections)
Serious events: 16 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MP Low Dose Group
n=87 participants at risk
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 participants at risk
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 participants at risk
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
n=331 participants at risk
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Shunt malfunction
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 2 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Surgical and medical procedures
CSF shunt operation
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Investigations
Electroencephalogram
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 2 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Spinal cord neoplasm
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
1.1%
1/87 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/331 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
1.1%
1/87 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/331 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
1.1%
1/87 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/331 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Nervous system disorders
Epilepsy
|
1.1%
1/87 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Nervous system disorders
Seizure
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.60%
2/331 • Number of events 2 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Nervous system disorders
Generalised tonic-clonic seizure
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Nervous system disorders
Status epilepticus
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
General disorders
Influenza like illness
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.60%
2/331 • Number of events 2 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Gastrointestinal disorders
Cyclic vomiting syndrome
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Infections and infestations
Bronchitis
|
2.3%
2/87 • Number of events 2 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.57%
1/176 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/331 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
1.1%
2/176 • Number of events 3 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/331 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Infections and infestations
Appendicitis
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Infections and infestations
Bronchitis bacterial
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Infections and infestations
Influenza
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Infections and infestations
Peritonitis
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Infections and infestations
Pertussis
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 2 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Infections and infestations
Pneumonia bacterial
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 2 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/87 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.00%
0/176 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
0.30%
1/331 • Number of events 1 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
Other adverse events
| Measure |
MP Low Dose Group
n=87 participants at risk
Participants in low dose group received intramuscular injections of 2 U/kg NT 201 (maximum of 50 U in participants with \>25 kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 2 U/kg (50 U for participants with \>25kg BW) to 5 U/kg (125 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP Mid Dose Group
n=87 participants at risk
Participants in mid dose group received intramuscular injections of 6 U/kg NT 201 (maximum of 150 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 6 U/kg (150 U for participants with \>25kg BW) to 15 U/kg (375 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
MP High Dose Group
n=176 participants at risk
Participants in high dose group received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of one of the UL on Day 1 of MP. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
OLEX (3 Injections)
n=331 participants at risk
Participants who completed MP and qualified for further participation in the study received intramuscular injections of 8 U/kg NT 201 (maximum of 200 U in participants with \>25kg BW) into spastic muscles of the UL on Day 1 of each of the three injection cycles of OLEX. If the contralateral UL or one or both LL were also treated, participants received additional doses of NT 201. The total body dose ranged from 8 U/kg (200 U for participants with \>25kg BW) to 20 U/kg (500 U for participants with \>25kg BW) depending on the combination of treated limbs and the participant's GMFCS level.
|
|---|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
5.7%
5/87 • Number of events 5 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
3.4%
3/87 • Number of events 5 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
3.4%
6/176 • Number of events 6 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
5.4%
18/331 • Number of events 22 • Baseline up to Week 66
The investigator asked the participant for adverse events (AEs) systematically at each visit.
|
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