XARA: 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
Sponsor
Merz Pharmaceuticals GmbH (Industry)
Overall Status
Completed
CT.gov ID
NCT02002884
Collaborator
(none)
351
32
3
53
11
0.2
Study Details
Study Description
Brief Summary
The purpose of this study is to determine whether injections of Botulinum toxin type A into muscles of one or both arms alone or in combination with injections into one or both legs are effective and safe in treating children/adolescents (age 2-17 years) with increased muscle tension/uncontrollable muscle stiffness (spasticity) due to cerebral palsy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
351 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Prospective, Multicenter, Randomized, Double-blind, Parallel-group, Dose-response Study of Three Doses Xeomin® (incobotulinumtoxinA, NT 201) for the Treatment of Upper Limb Spasticity Alone or Combined Upper and Lower Limb Spasticity in Children and Adolescents (Age 2 - 17 Years) With Cerebral Palsy
Actual Study Start Date
:
Mar 28, 2014
Actual Primary Completion Date
:
Jul 4, 2017
Actual Study Completion Date
:
Aug 28, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 8 Units per kg body weight incobotulinumtoxinA (Xeomin) 8 Units per kg body weight (maximum of 200 Units) will be injected per treated upper limb per injection cycle. Additionally, lower limb treatment may be administered, depending on clinical pattern: up to 300 Units per injection cycle. Overall maximum dose per injection cycle: 500 Units. |
Drug: IncobotulinumtoxinA (8 Units per kg body weight)
Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl); Mode of administration: intramuscular injection into spastic muscles.
Other Names:
|
| Experimental: 6 Units per kg body weight incobotulinumtoxinA (Xeomin) 6 Units per kg body weight (maximum of 150 Units) will be injected per treated upper limb per injection cycle. Additionally, lower limb treatment may be administered, depending on clinical pattern: up to 225 Units per injection cycle. Overall maximum dose per injection cycle: 375 Units. |
Drug: IncobotulinumtoxinA (6 Units per kg body weight)
Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl); Mode of administration: intramuscular injection into spastic muscles.
Other Names:
|
| Experimental: 2 Units per kg body weight incobotulinumtoxinA (Xeomin) 2 Units per kg body weight (maximum of 50 Units) will be injected per treated upper limb per injection cycle. Additionally, lower limb treatment may be administered, depending on clinical pattern: up to 75 Units per injection cycle. Overall maximum dose per injection cycle: 125 Units. |
Drug: IncobotulinumtoxinA (2 Units per kg body weight)
Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl); Mode of administration: intramuscular injection into spastic muscles.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- MP: Change From Baseline in Ashworth Scale (AS) in UL Primary Clinical Target Pattern at Week 4 [Baseline and Week 4]
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.
- Co-primary Variable MP: Investigator's Global Impression of Change Scale (GICS) at Week 4 [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.
Secondary Outcome Measures
- MP: Change From Baseline in AS Score of the Other Treated UL Main Clinical Target Pattern at Week 4 [Baseline and Week 4]
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.
- MP: Change From Baseline in AS Score in UL Treated Clenched Fist With Flexed Wrist at Week 4 [Baseline and Week 4]
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.
- MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4 [Baseline up to Week 4]
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.
- 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)' [Baseline, Weeks 4, 8, and 14]
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.
- MP: Child's/Adolescent's, and Parent's/Caregiver's GICS in UL at Week 4 [Week 4]
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.
- Number of Participants With Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Treatment Cycle [Baseline up to Week 66]
- Number of Participants With Occurrence of TEAEs of Special Interest (TEAESIs) Overall and Per Treatment Cycle [Baseline up to Week 66]
- Number of Participants With Occurrence of Serious TEAEs (TESAEs) Overall and Per Treatment Cycle [Baseline up to Week 66]
- Number of Participants With Occurrence of TEAEs Related to Treatment Overall and Per Treatment Cycle [Baseline up to Week 66]
- Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle [Baseline up to Week 66]
- Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle [Baseline up to Week 66]
- Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle [Baseline up to Week 66]
- Number of Participants With Occurrence of TEAEs Leading to Discontinuation Overall and Per Treatment Cycle [Baseline up to Week 66]
Eligibility Criteria
Criteria
Ages Eligible for Study:
2 Years
to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Female or male subject of 2 to 17 years of age (inclusive).
-
Uni- or bilateral Cerebral Palsy (CP) with clinical need for injections with NT 201 for the treatment of upper limb (UL) spasticity at least unilaterally.
-
Ashworth Scale (AS) score in the main clinical target patterns in this study:
-
Flexed elbow: AS≥2 in elbow flexors (at least unilaterally). and/or
-
Flexed Wrist: AS≥2 in wrist flexors (at least unilaterally).
- Clinical need according to the judgment of the investigator in one out of five treatment combinations (A-E, as shown below). AS score must be ≥2 for each target pattern chosen for injection at the Baseline Injection Visit V2.
A. UL(s) treatment only (GMFCS I-V):
A1) Unilateral treatment of UL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) for:
- At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW).
and
- Additional clinical patterns in the same limb (i.e., clenched fist, thumb in palm, and/or pronated forearm) with the remaining units until maximum dose of 8 U/kg BW (maximum of 200 U) for treatment of a single UL is reached.
or
A2) Bilateral treatment of UL spasticity with equal doses of 8 U/kg BW NT 201 (maximum of 200 U) to each UL. Dose per UL must be distributed between:
- At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW).
and
- Additional clinical patterns in the same limb (i.e., clenched fist, thumb in palm, and/or pronated forearm) with the remaining units until maximum dose of 8 U/kg BW (maximum of 200 U) for treatment of a single UL is reached.
B. Unilateral UL and unilateral lower limb (LL) treatment (GMFCS I-V):
B1) Unilateral treatment of UL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) for:
- At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW).
and
- Additional clinical patterns in the same limb (i.e., clenched fist, thumb in palm, and/or pronated forearm) with the remaining units until maximum dose of 8 U/kg BW (maximum of 200 U) for treatment of a single UL is reached.
plus
B2) Ipsilateral unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U). Dose to LL must be distributed to at least one of clinical target patterns pes equinus, flexed knee, adducted thigh, and extended great toe as clinically needed.
- Unilateral UL and bilateral LL treatment (GMFCS I-III)
C1) Unilateral treatment of UL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) for:
- At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW).
and
- Additional clinical patterns in the same limb (i.e., clenched fist, thumb in palm, and/or pronated forearm) with the remaining units until maximum dose of 8 U/kg BW (maximum of 200 U) for treatment of a single UL is reached.
plus
C2) Bilateral treatment of LL spasticity with 12 U/kg BW (maximum of 300 U). Dose must be distributed into at least one of clinical target patterns pes equinus, flexed knee, adducted thigh, and extended great toe, on each side. Dose distribution may vary between sides as clinically needed.
- Unilateral UL and bilateral LL treatment (GMFCS IV and V)
D1) Unilateral treatment of UL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) for:
- At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW).
and
- Additional clinical patterns in the same limb (i.e., clenched fist, thumb in palm, and/or pronated forearm) with the remaining units until maximum dose of 8 U/kg BW (maximum of 200 U) for treatment of a single UL is reached.
plus
D2) Bilateral treatment of LL spasticity with 8 U/kg BW (maximum of 200 U). Dose must be distributed into at least one of clinical target patterns pes equinus, flexed knee, adducted thigh, and extended great toe, on each side. Dose distribution may vary between sides as clinically needed.
- Bilateral UL treatment and bilateral LL treatment (GMFCS I-III)
E1) Bilateral treatment of UL spasticity with equal doses of 8 U/kg BW NT 201 (maximum of 200 U) to each UL. Dose per UL must be distributed between
-
At least one of the main clinical target patterns flexed elbow (4 U/kg BW) and/or flexed wrist (2 U/kg BW) and
-
Additional clinical patterns in the same limb (i.e., clenched fist, thumb in palm, and/or pronated forearm) with the remaining units until maximum dose of 8 U/kg BW (maximum of 200 U) for treatment of a single UL is reached.
plus
E2) Bilateral treatment of LL spasticity with 4 U/kg BW (maximum of 100 U). Dose must be distributed into at least one of clinical target patterns pes equinus, flexed knee, adducted thigh, and extended great toe, on each side. Dose distribution may vary between sides as clinically needed.
Exclusion Criteria:
Pre-treated (non-naïve) subjects must not have received BoNT treatment within the last 14 weeks prior to Screening Visit (V1) in any indication.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Merz Investigational Site #001286 | Gulf Breeze | Florida | United States | 32561 |
| 2 | Merz Investigational Site #001284 | Loxahatchee Groves | Florida | United States | 33470 |
| 3 | Merz Investigational Site #001285 | Savannah | Georgia | United States | 31405 |
| 4 | Merz Investigational Site #001186 | Chicago | Illinois | United States | 60611 |
| 5 | Merz Investigational Site No. #001302 | Royal Oak | Michigan | United States | 48073 |
| 6 | Merz Investigational Site #001283 | Columbia | Missouri | United States | 65212 |
| 7 | Merz Investigational Site #054010 | Godoy Cruz | Provincia De Mendoza | Argentina | M5501 |
| 8 | Merz Investigational Site #054005 | Caba | Argentina | CP 1428 | |
| 9 | Merz Investigational Site #052023 | Aguascalientes | Mexico | 20127 | |
| 10 | Merz Investigational Site #052003 | Guadalajara | Mexico | 44280 | |
| 11 | Merz Investigational Site #052024 | Mexico City | Mexico | 04530 | |
| 12 | Merz Investigational Site #052022 | Mexico City | Mexico | 06700 | |
| 13 | Merz Investigational Site #052027 | Monterrey | Mexico | 64060 | |
| 14 | Merz Investigational Site #052028 | Monterrey | Mexico | 64710 | |
| 15 | Merz Investigational Site #052026 | Zapopan | Mexico | 45030 | |
| 16 | Merz Investigational Site #048089 | Bialystok | Poland | 15-274 | |
| 17 | Merz Investigational Site #048063 | Gdansk | Poland | 80-389 | |
| 18 | Merz Investigational Site #048059 | Krakow | Poland | 30-539 | |
| 19 | Merz Investigational Site #048084 | Lublin | Poland | 20-828 | |
| 20 | Merz Investigational Site #048094 | Poznan | Poland | 60-480 | |
| 21 | Merz Investigational Site #048075 | Sandomierz | Poland | 27-600 | |
| 22 | Merz Investigational Site #048060 | Wiazowna | Poland | 05-462 | |
| 23 | Merz Investigational Site #007014 | Kazan | Russian Federation | 420097 | |
| 24 | Merz Investigational Site #007015 | Khabarovsk | Russian Federation | 680038 | |
| 25 | Merz Investigational Site #007018 | Novosibirsk | Russian Federation | 630091 | |
| 26 | Merz Investigational Site #007298 | Saint Petersburg | Russian Federation | 192148 | |
| 27 | Merz Investigational Site #007013 | Smolensk | Russian Federation | 214019 | |
| 28 | Merz Investigational Site #007019 | Stavropol | Russian Federation | 355029 | |
| 29 | Merz Investigational Site #380001 | Dnipropetrovsk | Ukraine | 49000 | |
| 30 | Merz Investigational Site #380005 | Kharkiv | Ukraine | 61068 | |
| 31 | Merz Investigational Site #380002 | Kyiv | Ukraine | 04209 | |
| 32 | Merz Investigational Site #380003 | Odessa | Ukraine | 65012 |
Sponsors and Collaborators
- Merz Pharmaceuticals GmbH
Investigators
- Study Director: Merz Medical Expert, Merz Pharmaceuticals GmbH
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier:
NCT02002884
Other Study ID Numbers:
- MRZ60201_3072_1
- 2012-005496-14
First Posted:
Dec 6, 2013
Last Update Posted:
Aug 5, 2021
Last Verified:
Jul 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Merz Pharmaceuticals GmbH
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted at 28 investigative sites in Mexico, Argentina, Russian federation, Ukraine, United States and Poland. |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group | OLEX (3 Injections) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Period Title: Main Period (MP) | ||||
| STARTED | 87 | 88 | 176 | 0 |
| Treated | 87 | 87 | 176 | 0 |
| COMPLETED | 81 | 82 | 168 | 0 |
| NOT COMPLETED | 6 | 6 | 8 | 0 |
| Period Title: Main Period (MP) | ||||
| STARTED | 0 | 0 | 0 | 331 |
| COMPLETED | 0 | 0 | 0 | 281 |
| NOT COMPLETED | 0 | 0 | 0 | 50 |
Baseline Characteristics
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group | Total |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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 of all reporting groups |
| Overall Participants | 87 | 88 | 176 | 351 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
7.2
(4.70)
|
7.4
(4.13)
|
7.3
(4.40)
|
7.3
(4.40)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
38
43.7%
|
31
35.2%
|
62
35.2%
|
131
37.3%
|
| Male |
49
56.3%
|
57
64.8%
|
114
64.8%
|
220
62.7%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Hispanic or Latino |
16
18.4%
|
26
29.5%
|
45
25.6%
|
87
24.8%
|
| Not Hispanic or Latino |
71
81.6%
|
62
70.5%
|
131
74.4%
|
264
75.2%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Black or African American |
3
3.4%
|
2
2.3%
|
2
1.1%
|
7
2%
|
| White |
81
93.1%
|
75
85.2%
|
160
90.9%
|
316
90%
|
| Other |
3
3.4%
|
11
12.5%
|
14
8%
|
28
8%
|
Outcome Measures
| Title | MP: Change From Baseline in Ashworth Scale (AS) in UL Primary Clinical Target Pattern at Week 4 |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 87 | 176 |
| High versus low |
-0.93
(0.078)
|
-1.15
(0.056)
|
|
| Mid versus low |
-0.96
(0.082)
|
-1.02
(0.082)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MP Low Dose Group, MP High Dose Group |
|---|---|---|
| Comments | LS-Means are from mixed model with treatment group, pooled site and pre-treatment status included as fixed factors and AS at baseline, Gross Motor Function Classification System-Extended and Revised (GMFCS-E&R) level at screening included as covariates. For MMRM visit*treatment is interaction term repeated factor. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.017 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean difference |
| Estimated Value | -0.22 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to -0.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | MP Low Dose Group, MP Mid Dose Group |
|---|---|---|
| Comments | LS-Means are from mixed model with treatment group, pooled site and pre-treatment status included as fixed factors and AS at baseline, GMFCS-E&R level at screening included as covariates. For MMRM visit*treatment is interaction term repeated factor. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.546 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS-Mean difference |
| Estimated Value | -0.07 | |
| Confidence Interval |
(2-Sided) 95% -0.29 to 0.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Co-primary Variable MP: Investigator's Global Impression of Change Scale (GICS) at Week 4 |
|---|---|
| Description | 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. |
| Time Frame | Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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]). |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 87 | 176 |
| High versus low |
1.55
(0.083)
|
1.64
(0.062)
|
|
| Mid versus low |
1.57
(0.089)
|
1.44
(0.092)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | MP Low Dose Group, MP High Dose Group |
|---|---|---|
| Comments | LS-Means are from analysis of covariance (ANCOVA) with treatment group, pooled site and pretreatment status included as fixed factors and maximum AS score of the two possible primary target patterns flexed elbow or flexed wrist baseline, GMFCS-E&R level at screening included as covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.34 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS-Mean difference |
| Estimated Value | 0.09 | |
| Confidence Interval |
(2-Sided) 95% -0.1 to 0.28 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | MP Low Dose Group, MP Mid Dose Group |
|---|---|---|
| Comments | LS-Means are from ANCOVA with treatment group, pooled site and pre-treatment status included as fixed factors and maximum AS score of the two possible primary target patterns flexed elbow or flexed wrist baseline, GMFCS-E&R level at screening included as covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | = 0.297 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS-Mean difference |
| Estimated Value | -0.12 | |
| Confidence Interval |
(2-Sided) 95% -0.36 to 0.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | MP: Change From Baseline in AS Score of the Other Treated UL Main Clinical Target Pattern at Week 4 |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 87 | 176 |
| High versus low |
-1.03
(0.083)
|
-1.13
(0.061)
|
|
| Mid versus low |
-1.08
(0.087)
|
-1.22
(0.090)
|
| Title | MP: Change From Baseline in AS Score in UL Treated Clenched Fist With Flexed Wrist at Week 4 |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 87 | 176 |
| High versus low |
-0.53
(0.212)
|
-1.00
(0.133)
|
|
| Mid versus low |
-0.070
(0.202)
|
-1.04
(0.176)
|
| Title | MP: Change From Baseline in AS Score for Each Treated Clinical Pattern of the UL at Week 4 |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 87 | 176 |
| Flexed elbow: High versus Low |
-0.99
(0.076)
|
-1.18
(0.056)
|
|
| Flexed elbow: Mid versus Low |
-1.01
(0.081)
|
-1.17
(0.082)
|
|
| Flexed wrist: High versus Low |
-0.96
(0.085)
|
-1.08
(0.061)
|
|
| Flexed wrist: Mid versus Low |
-1.01
(0.087)
|
-1.05
(0.087)
|
|
| Clenched fist: High versus Low |
-0.64
(0.136)
|
-1.09
(0.096)
|
|
| Clenched fist: Mid versus Low |
-0.58
(0.145)
|
-0.87
(0.141)
|
|
| Thumb in palm: High versus Low |
-0.88
(0.116)
|
-1.11
(0.083)
|
|
| Thumb in palm: Mid versus Low |
-0.93
(0.131)
|
-1.14
(0.123)
|
|
| Pronated forearm: High versus Low |
-0.88
(0.080)
|
-1.02
(0.058)
|
|
| Pronated forearm: Mid versus Low |
-0.87
(0.086)
|
-0.94
(0.088)
|
| Title | 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)' |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Weeks 4, 8, and 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 87 | 176 |
| UL, Participant, Week 4 High versus low |
-0.42
(0.217)
|
-0.75
(0.199)
|
|
| UL, Participant, Week 4 Mid versus low |
-0.39
(0.256)
|
-0.67
(0.289)
|
|
| UL, Participant, Week 8 High versus low |
-0.52
(0.206)
|
-0.64
(0.188)
|
|
| UL, Participant, Week 8 Mid versus low |
-0.63
(0.259)
|
-0.55
(0.290)
|
|
| UL, Participant, Week 14 High versus low |
-0.56
(0.217)
|
-0.59
(0.202)
|
|
| UL, Participant, Week 14 Mid versus low |
-0.66
(0.327)
|
-0.59
(0.361)
|
|
| UL, P/C, Week 4 High versus low |
-0.46
(0.102)
|
-0.44
(0.076)
|
|
| UL, P/C, Week 4 Mid versus low |
-0.43
(0.106)
|
-0.28
(0.115)
|
|
| UL, P/C, Week 8 High versus low |
-0.40
(0.095)
|
-0.44
(0.070)
|
|
| UL, P/C, Week 8 Mid versus low |
-0.43
(0.100)
|
-0.34
(0.109)
|
|
| UL, P/C, Week 14 High versus Low |
-0.23
(0.105)
|
-0.24
(0.071)
|
|
| UL, P/C, Week 14 Mid versus Low |
-0.31
(0.100)
|
-0.25
(0.107)
|
|
| LL, Participant, Week 4 High versus Low |
-0.74
(0.282)
|
-0.62
(0.250)
|
|
| LL, Participant, Week 4 Mid versus Low |
-0.46
(0.305)
|
-0.55
(0.321)
|
|
| LL, Participant, Week 8 High versus Low |
-1.04
(0.241)
|
-0.69
(0.218)
|
|
| LL, Participant, Week 8 Mid versus Low |
-0.90
(0.261)
|
-0.81
(0.284)
|
|
| LL, Participant, Week 14 High versus Low |
-0.71
(0.275)
|
-0.57
(0.245)
|
|
| LL, Participant, Week 14 Mid versus Low |
-0.67
(0.315)
|
-0.63
(0.335)
|
|
| LL, P/C, Week 4 High versus Low |
-0.50
(0.105)
|
-0.52
(0.077)
|
|
| LL, P/C, Week 4 Mid versus Low |
-0.46
(0.103)
|
-0.42
(0.111)
|
|
| LL, P/C, Week 8 High versus Low |
-0.56
(0.098)
|
-0.51
(0.074)
|
|
| LL, P/C, Week 8 Mid versus Low |
-0.52
(0.102)
|
-0.36
(0.111)
|
|
| LL, P/C, Week 14 High versus Low |
-0.33
(0.108)
|
-0.32
(0.078)
|
|
| LL, P/C, Week 14 Mid versus Low |
-0.37
(0.086)
|
-0.31
(0.090)
|
| Title | MP: Child's/Adolescent's, and Parent's/Caregiver's GICS in UL at Week 4 |
|---|---|
| Description | 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. |
| Time Frame | Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 87 | 176 |
| Participant: High versus Low |
1.51
(0.153)
|
1.63
(0.139)
|
|
| Participant: Mid versus Low |
1.53
(0.180)
|
1.48
(0.190)
|
|
| Parent/Caregiver: High versus Low |
1.41
(0.087)
|
1.60
(0.065)
|
|
| Parent/Caregiver: Mid versus Low |
1.36
(0.094)
|
1.29
(0.097)
|
| Title | Number of Participants With Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Treatment Cycle |
|---|---|
| Description | |
| Time Frame | Baseline up to Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group | OLEX (3 Injections) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 87 | 87 | 176 | 331 |
| Overall |
21
24.1%
|
13
14.8%
|
42
23.9%
|
114
32.5%
|
| First injection cycle (MP) |
21
24.1%
|
13
14.8%
|
42
23.9%
|
|
| Second injection cycle (OLEX) |
64
73.6%
|
|||
| Third injection cycle (OLEX) |
42
48.3%
|
|||
| Fourth injection cycle (OLEX) |
48
55.2%
|
| Title | Number of Participants With Occurrence of TEAEs of Special Interest (TEAESIs) Overall and Per Treatment Cycle |
|---|---|
| Description | |
| Time Frame | Baseline up to Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group | OLEX (3 Injections) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 87 | 87 | 176 | 331 |
| Overall |
1
1.1%
|
1
1.1%
|
1
0.6%
|
5
1.4%
|
| First injection cycle (MP) |
1
1.1%
|
1
1.1%
|
1
0.6%
|
|
| Second injection cycle (OLEX) |
2
2.3%
|
|||
| Third injection cycle (OLEX) |
3
3.4%
|
|||
| Fourth injection cycle (OLEX) |
1
1.1%
|
| Title | Number of Participants With Occurrence of Serious TEAEs (TESAEs) Overall and Per Treatment Cycle |
|---|---|
| Description | |
| Time Frame | Baseline up to Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group | OLEX (3 Injections) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 87 | 87 | 176 | 331 |
| Overall |
2
2.3%
|
1
1.1%
|
2
1.1%
|
16
4.6%
|
| First injection cycle (MP) |
2
2.3%
|
1
1.1%
|
2
1.1%
|
|
| Second injection cycle (OLEX) |
7
8%
|
|||
| Third injection cycle (OLEX) |
9
10.3%
|
|||
| Fourth injection cycle (OLEX) |
3
3.4%
|
| Title | Number of Participants With Occurrence of TEAEs Related to Treatment Overall and Per Treatment Cycle |
|---|---|
| Description | |
| Time Frame | Baseline up to Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group | OLEX (3 Injections) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 87 | 87 | 176 | 331 |
| Overall |
0
0%
|
0
0%
|
3
1.7%
|
5
1.4%
|
| First injection cycle (MP) |
0
0%
|
0
0%
|
3
1.7%
|
|
| Second injection cycle (OLEX) |
2
2.3%
|
|||
| Third injection cycle (OLEX) |
2
2.3%
|
|||
| Fourth injection cycle (OLEX) |
1
1.1%
|
| Title | Number of Participants With Occurrence of TEAEs by Worst Intensity Overall and Per Treatment Cycle |
|---|---|
| Description | |
| Time Frame | Baseline up to Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group | OLEX (3 Injections) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 87 | 87 | 176 | 331 |
| Overall: Mild |
15
17.2%
|
10
11.4%
|
33
18.8%
|
62
17.7%
|
| Overall: Moderate |
6
6.9%
|
2
2.3%
|
7
4%
|
44
12.5%
|
| Overall: Severe |
0
0%
|
1
1.1%
|
2
1.1%
|
8
2.3%
|
| First injection cycle (MP): Mild |
15
17.2%
|
10
11.4%
|
33
18.8%
|
|
| First injection cycle (MP): Moderate |
6
6.9%
|
2
2.3%
|
7
4%
|
|
| First injection cycle (MP): Severe |
0
0%
|
1
1.1%
|
2
1.1%
|
|
| Second injection cycle (OLEX): Mild |
43
49.4%
|
|||
| Second injection cycle (OLEX): Moderate |
18
20.7%
|
|||
| Second injection cycle (OLEX): Severe |
3
3.4%
|
|||
| Third injection cycle (OLEX): Mild |
23
26.4%
|
|||
| Third injection cycle (OLEX): Moderate |
15
17.2%
|
|||
| Third injection cycle (OLEX): Severe |
4
4.6%
|
|||
| Fourth injection cycle (OLEX): Mild |
28
32.2%
|
|||
| Fourth injection cycle (OLEX): Moderate |
19
21.8%
|
|||
| Fourth injection cycle (OLEX): Severe |
1
1.1%
|
| Title | Number of Participants With Occurrence of TEAEs by Worst Causal Relationship Overall and Per Treatment Cycle |
|---|---|
| Description | |
| Time Frame | Baseline up to Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group | OLEX (3 Injections) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 87 | 87 | 176 | 331 |
| Overall: Related |
0
0%
|
0
0%
|
3
1.7%
|
5
1.4%
|
| Overall: Not related |
21
24.1%
|
13
14.8%
|
39
22.2%
|
109
31.1%
|
| First injection cycle (MP): Related |
0
0%
|
0
0%
|
3
1.7%
|
|
| First injection cycle (MP): Not related |
21
24.1%
|
13
14.8%
|
39
22.2%
|
|
| Second injection cycle (OLEX): Related |
2
2.3%
|
|||
| Second injection cycle (OLEX): Not related |
62
71.3%
|
|||
| Third injection cycle (OLEX): Related |
2
2.3%
|
|||
| Third injection cycle (OLEX): Not related |
40
46%
|
|||
| Fourth injection cycle (OLEX): Related |
1
1.1%
|
|||
| Fourth injection cycle (OLEX): Not related |
47
54%
|
| Title | Number of Participants With Occurrence of TEAEs by Final Outcome Overall and Per Treatment Cycle |
|---|---|
| Description | |
| Time Frame | Baseline up to Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group | OLEX (3 Injections) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 87 | 87 | 176 | 331 |
| Overall: Resolved |
18
20.7%
|
10
11.4%
|
39
22.2%
|
96
27.4%
|
| Overall: Resolved with sequelae |
1
1.1%
|
0
0%
|
0
0%
|
1
0.3%
|
| Overall: Resolving |
0
0%
|
2
2.3%
|
1
0.6%
|
7
2%
|
| Overall: Not resolved |
2
2.3%
|
1
1.1%
|
1
0.6%
|
8
2.3%
|
| Overall: Unknown |
0
0%
|
0
0%
|
1
0.6%
|
2
0.6%
|
| Overall: Fatal |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| First injection cycle (MP): Resolved |
18
20.7%
|
10
11.4%
|
39
22.2%
|
|
| First injection cycle (MP): Resolved with sequelae |
1
1.1%
|
0
0%
|
0
0%
|
|
| First injection cycle (MP): Resolving |
0
0%
|
2
2.3%
|
1
0.6%
|
|
| First injection cycle (MP): Not resolved |
2
2.3%
|
1
1.1%
|
1
0.6%
|
|
| First injection cycle (MP): Unknown |
0
0%
|
0
0%
|
1
0.6%
|
|
| First injection cycle (MP): Fatal |
0
0%
|
0
0%
|
0
0%
|
|
| Second injection cycle (OLEX): Resolved |
57
65.5%
|
|||
| Secondinjection cycle(OLEX):Resolved with sequelae |
0
0%
|
|||
| Second injection cycle (OLEX): Resolving |
3
3.4%
|
|||
| Second injection cycle (OLEX): Not resolved |
4
4.6%
|
|||
| Second injection cycle (OLEX): Unknown |
0
0%
|
|||
| Second injection cycle (OLEX): Fatal |
0
0%
|
|||
| Third injection cycle (OLEX): Resolved |
37
42.5%
|
|||
| Third injection cycle(OLEX):Resolved with sequelae |
0
0%
|
|||
| Third injection cycle (OLEX): Resolving |
0
0%
|
|||
| Third injection cycle (OLEX): Not resolved |
4
4.6%
|
|||
| Third injection cycle (OLEX): Unknown |
1
1.1%
|
|||
| Third injection cycle (OLEX): Fatal |
0
0%
|
|||
| Fourth injection cycle (OLEX): Resolved |
39
44.8%
|
|||
| Fourthinjection cycle(OLEX):Resolved with sequelae |
1
1.1%
|
|||
| Fourth injection cycle (OLEX): Resolving |
4
4.6%
|
|||
| Fourth injection cycle (OLEX): Not resolved |
2
2.3%
|
|||
| Fourth injection cycle (OLEX): Unknown |
2
2.3%
|
|||
| Fourth injection cycle (OLEX): Fatal |
0
0%
|
| Title | Number of Participants With Occurrence of TEAEs Leading to Discontinuation Overall and Per Treatment Cycle |
|---|---|
| Description | |
| Time Frame | Baseline up to Week 66 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group | OLEX (3 Injections) |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 87 | 87 | 176 | 331 |
| Overall |
0
0%
|
1
1.1%
|
1
0.6%
|
5
1.4%
|
| First injection cycle (MP) |
0
0%
|
1
1.1%
|
1
0.6%
|
|
| Second injection cycle (OLEX) |
3
3.4%
|
|||
| Third injection cycle (OLEX) |
2
2.3%
|
|||
| Fourth injection cycle (OLEX) |
0
0%
|
Adverse Events
| Time Frame | Baseline up to Week 66 | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The investigator asked the participant for adverse events (AEs) systematically at each visit. | |||||||
| Arm/Group Title | MP Low Dose Group | MP Mid Dose Group | MP High Dose Group | OLEX (3 Injections) | ||||
| Arm/Group Description | 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. | 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. | 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. | 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. | ||||
All Cause Mortality |
||||||||
| MP Low Dose Group | MP Mid Dose Group | MP High Dose Group | OLEX (3 Injections) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/87 (0%) | 0/87 (0%) | 0/176 (0%) | 0/331 (0%) | ||||
Serious Adverse Events |
||||||||
| MP Low Dose Group | MP Mid Dose Group | MP High Dose Group | OLEX (3 Injections) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/87 (2.3%) | 1/87 (1.1%) | 2/176 (1.1%) | 16/331 (4.8%) | ||||
| Gastrointestinal disorders | ||||||||
| Hiatus hernia | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 2/331 (0.6%) | 2 |
| Cyclic vomiting syndrome | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Gastrooesophageal reflux disease | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Vomiting | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| General disorders | ||||||||
| Influenza like illness | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Infections and infestations | ||||||||
| Bronchitis | 2/87 (2.3%) | 2 | 0/87 (0%) | 0 | 1/176 (0.6%) | 1 | 0/331 (0%) | 0 |
| Pneumonia | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 2/176 (1.1%) | 3 | 0/331 (0%) | 0 |
| Appendicitis | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Bronchitis bacterial | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Influenza | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Peritonitis | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Pertussis | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Pharyngitis | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 2 |
| Pneumonia bacterial | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 2 |
| Upper respiratory tract infection | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Urinary tract infection | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Injury, poisoning and procedural complications | ||||||||
| Shunt malfunction | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 2 |
| Thermal burn | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Investigations | ||||||||
| Electroencephalogram | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 2 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Spinal cord neoplasm | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Nervous system disorders | ||||||||
| Brain oedema | 0/87 (0%) | 0 | 1/87 (1.1%) | 1 | 0/176 (0%) | 0 | 0/331 (0%) | 0 |
| Epilepsy | 1/87 (1.1%) | 1 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Seizure | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 2/331 (0.6%) | 2 |
| Generalised tonic-clonic seizure | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Status epilepticus | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Aspiration | 0/87 (0%) | 0 | 1/87 (1.1%) | 1 | 0/176 (0%) | 0 | 0/331 (0%) | 0 |
| Respiratory arrest | 0/87 (0%) | 0 | 1/87 (1.1%) | 1 | 0/176 (0%) | 0 | 0/331 (0%) | 0 |
| Pneumonia aspiration | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||
| Angioedema | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
| Surgical and medical procedures | ||||||||
| CSF shunt operation | 0/87 (0%) | 0 | 0/87 (0%) | 0 | 0/176 (0%) | 0 | 1/331 (0.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||
| MP Low Dose Group | MP Mid Dose Group | MP High Dose Group | OLEX (3 Injections) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/87 (5.7%) | 3/87 (3.4%) | 6/176 (3.4%) | 18/331 (5.4%) | ||||
| Infections and infestations | ||||||||
| Nasopharyngitis | 5/87 (5.7%) | 5 | 3/87 (3.4%) | 5 | 6/176 (3.4%) | 6 | 18/331 (5.4%) | 22 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Public Disclosure Manager |
|---|---|
| Organization | Merz Pharmaceuticals GmbH |
| Phone | +49 69 1503 1 |
| clinicaltrials@merz.com |
Responsible Party:
Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier:
NCT02002884
Other Study ID Numbers:
- MRZ60201_3072_1
- 2012-005496-14
First Posted:
Dec 6, 2013
Last Update Posted:
Aug 5, 2021
Last Verified:
Jul 1, 2020