Trial Outcomes & Findings for Dysport® Pediatric Lower Limb Spasticity Follow-on Study (NCT NCT01251380)

NCT ID: NCT01251380

Last Updated: 2022-09-28

Results Overview

Adverse events (AEs) were monitored from the time of informed consent to the end of the study. All AEs were elicited by direct, non-leading questioning or by spontaneous reports.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 216 participants
• Primary outcome timeframe: From baseline (Day 1) until end of study (Week 40) of Cycle 1 and up to Week 28 of Cycles 2 to 4.
• Results posted on: 2022-09-28

Participant Flow

This was a multicentre study performed at 27 investigational sites in France, Mexico, Turkey, Poland, Chile and the United States of America (USA). Twenty six sites recruited at least one subject and the other site was inactive.

Of 216 subjects enrolled in this open label study from Study Y-55-52120-141, 203 went straight into Cycle 1. 13 subjects were not considered eligible for re-treatment at end (all of whom had received Dysport) and as per study design they entered into the observational phase of Study 147. Of these 13, 4 subjects entered Cycle 1 at a later date.

Participant milestones

Measure	Total Dysport Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Overall Study STARTED	216
Overall Study Cycle 1	207
Overall Study Cycle 2	175
Overall Study Cycle 3	86
Overall Study Cycle 4	11
Overall Study COMPLETED	194
Overall Study NOT COMPLETED	22

Reasons for withdrawal

Measure	Total Dysport Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Overall Study Other (Not otherwise specified)	12
Overall Study Withdrawal by Subject	6
Overall Study Lack of Efficacy	1
Overall Study Adverse Event	1
Overall Study Lost to Follow-up	2

Baseline Characteristics

Dysport® Pediatric Lower Limb Spasticity Follow-on Study

Baseline characteristics by cohort

Measure	Total Dysport n=216 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Age, Continuous	5.9 years STANDARD_DEVIATION 3.3 • n=5 Participants
Age, Customized Children (2-9 years)	183 participants n=5 Participants
Age, Customized Children (10-17 years)	33 participants n=5 Participants
Sex: Female, Male Female	86 Participants n=5 Participants
Sex: Female, Male Male	130 Participants n=5 Participants
Race/Ethnicity, Customized Black/African American	5 participants n=5 Participants
Race/Ethnicity, Customized Caucasian/White	159 participants n=5 Participants
Race/Ethnicity, Customized American Indian/Alaskan Native	1 participants n=5 Participants
Race/Ethnicity, Customized Multiple	51 participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline (Day 1) until end of study (Week 40) of Cycle 1 and up to Week 28 of Cycles 2 to 4.

Population: Safety Population - all enrolled subjects. One subject received placebo in the DB study and two treatment cycles of Dysport in the OL study. However, as both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycle 1 and Treatment Cycle 2), the subject was excluded from the analysis (no TEAEs reported for this subject).

Adverse events (AEs) were monitored from the time of informed consent to the end of the study. All AEs were elicited by direct, non-leading questioning or by spontaneous reports.

Outcome measures

Measure	Total Dysport n=215 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. Any TEAE	177 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. Intensity of TEAEs - at least 1 is Severe	5 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. Intensity of TEAEs - at least 1 is Moderate	91 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. Intensity of TEAEs - at least 1 is Mild	151 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. Intensity of TEAEs - at least 1 is Missing	1 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. Causality of TEAEs - at least 1 is Related	29 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. Causality of TEAEs - at least 1 is Not Related	172 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. Causality of TEAEs - at least 1 is Missing	0 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. TEAEs - at least 1 is Related & Severe	0 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. TEAEs - at least 1 is Related & Moderate	9 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. TEAEs - at least 1 is Related & Mild	23 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. TEAEs - at least 1 is Not Related & Severe	5 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. TEAEs - at least 1 is Not Related & Moderate	87 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. TEAEs - at least 1 is Not Related & Mild	145 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. Any TEAEs leading to Study Withdrawal	1 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. Any TEAEs leading to Death	0 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. Any Serious Adverse Events (SAEs)	7 participants	—	—
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Reported in the Double Blind (DB) + Open Label (OL) Period. Any Non-serious TEAEs	175 participants	—	—

SECONDARY outcome

Timeframe: DB baseline; Weeks 4 and 12 of Treatment Cycles 1 to 3; Week 4 of Treatment Cycle 4

Population: Intent-to-treat (ITT) population where n represents number of subjects with data. For Dysport 10 U/kg and 15 U/kg, the actual administered doses in the GSC of the (most) affected leg were \>7.5 to ≤12.5 U/kg and \>12.5 to ≤17.5 U/kg, respectively, in the OL study. The analysis excluded subjects with doses ≤7.5 or \>17.5 U/kg.

Baseline for the 'change from DB baseline' was defined as the baseline of Study 141 for all treatment cycles. The Modified Ashworth Scale (MAS) is a 6-point scale which measures the intensity of muscle tone by measuring the resistance of the muscle to passive lengthening or stretching. The investigator graded muscle tone in the GSC from 0 (no increase in tone) to 4 (affected parts rigid in flexion or extension).

Outcome measures

Measure	Total Dysport n=170 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Change From Baseline (in the DB Study) in the MAS Score in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 1, Week 4 (n=170)	-1.0 units on a scale Standard Deviation 0.9	—	—
Mean Change From Baseline (in the DB Study) in the MAS Score in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 1, Week 12 (n=157)	-0.8 units on a scale Standard Deviation 0.8	—	—
Mean Change From Baseline (in the DB Study) in the MAS Score in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 2, Week 4 (n=122)	-1.1 units on a scale Standard Deviation 0.9	—	—
Mean Change From Baseline (in the DB Study) in the MAS Score in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 2, Week 12 (n=93)	-0.9 units on a scale Standard Deviation 0.9	—	—
Mean Change From Baseline (in the DB Study) in the MAS Score in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 3, Week 4 (n=66)	-1.0 units on a scale Standard Deviation 0.8	—	—
Mean Change From Baseline (in the DB Study) in the MAS Score in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 3, Week 12 (n=35)	-0.7 units on a scale Standard Deviation 1.0	—	—
Mean Change From Baseline (in the DB Study) in the MAS Score in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 4, Week 4 (n=8)	-0.4 units on a scale Standard Deviation 0.5	—	—

SECONDARY outcome

Timeframe: Baseline and Weeks 4 and 12 of Treatment Cycles 1 to 3; Baseline and Week 4 of Treatment Cycle 4.

Population: ITT population where n represents number of subjects with data. For Dysport 5 U/kg and 10 U/kg, the actual administered doses in the hamstring of the (most) affected leg were \>3 to ≤7.5 U/kg and \>7.5 to ≤12.5 U/kg, respectively. Analysis excluded subjects with doses ≤3 or \>12.5 U/kg. Only data from subjects injected in the hamstring are presented.

Baseline was defined as the value obtained prior to the first injection in the hamstrings. The MAS is a 6-point scale which measures the intensity of muscle tone by measuring the resistance of the muscle to passive lengthening or stretching. The investigator graded muscle tone in the GSC from 0 (no increase in tone) to 4 (affected parts rigid in flexion or extension).

Outcome measures

Measure	Total Dysport n=33 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in the MAS Score in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 1, Week 4 (n=25)	-0.6 units on a scale Standard Deviation 0.7	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in the MAS Score in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 1, Week 12 (n=24)	-0.8 units on a scale Standard Deviation 0.8	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in the MAS Score in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 2, Week 4 (n=33)	-0.5 units on a scale Standard Deviation 0.9	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in the MAS Score in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 3, Week 12 (n=5)	-0.6 units on a scale Standard Deviation 0.5	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in the MAS Score in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 4, Week 4 (n=2)	-0.5 units on a scale Standard Deviation 0.7	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in the MAS Score in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 2, Week 12 (n=21)	-0.3 units on a scale Standard Deviation 0.9	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in the MAS Score in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 3, Week 4 (n=13)	-0.2 units on a scale Standard Deviation 0.8	—	—

SECONDARY outcome

Timeframe: Baseline and Weeks 4 and 12 of Treatment Cycles 2 and 3.

Population: ITT population where n represents number of subjects with data. Only data from subjects injected in the upper limb muscle groups are presented. TC = Treatment Cycle.

Baseline was defined as the value obtained prior to the first injection in the upper limb(s). The MAS is a 6-point scale which measures the intensity of muscle tone by measuring the resistance of the muscle to passive lengthening or stretching. The investigator graded muscle tone in the GSC from 0 (no increase in tone) to 4 (affected parts rigid in flexion or extension). No subjects were treated in the upper limb in Treatment Cycle 4.

Outcome measures

Measure	Total Dysport n=14 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Change From Baseline (Prior to the First Injection Cycle in Upper Limb Muscle Groups) in the Mean MAS Score for All Injected Upper Limb Muscle Groups From Treatment Cycle 2 Onwards TC 2: Elbow Flexors at Week 4 (n=14)	-1.2 units on a scale Standard Deviation 0.9	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in Upper Limb Muscle Groups) in the Mean MAS Score for All Injected Upper Limb Muscle Groups From Treatment Cycle 2 Onwards TC 2: Elbow Flexors at Week 12 (n=12)	-1.1 units on a scale Standard Deviation 0.8	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in Upper Limb Muscle Groups) in the Mean MAS Score for All Injected Upper Limb Muscle Groups From Treatment Cycle 2 Onwards TC 2: Wrist Flexors at Week 4 (n=11)	-1.6 units on a scale Standard Deviation 0.8	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in Upper Limb Muscle Groups) in the Mean MAS Score for All Injected Upper Limb Muscle Groups From Treatment Cycle 2 Onwards TC 2: Wrist Flexors at Week 12 (n=8)	-1.0 units on a scale Standard Deviation 0.9	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in Upper Limb Muscle Groups) in the Mean MAS Score for All Injected Upper Limb Muscle Groups From Treatment Cycle 2 Onwards TC 3: Elbow Flexors at Week 4 (n=2)	1.0 units on a scale Standard Deviation 0.0	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in Upper Limb Muscle Groups) in the Mean MAS Score for All Injected Upper Limb Muscle Groups From Treatment Cycle 2 Onwards TC 3: Elbow Flexors at Week 12 (n=1)	-1.0 units on a scale Standard Deviation NA Non calculable as N=1	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in Upper Limb Muscle Groups) in the Mean MAS Score for All Injected Upper Limb Muscle Groups From Treatment Cycle 2 Onwards TC 3: Wrist Flexors at Week 4 (n=5)	-1.4 units on a scale Standard Deviation 0.9	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in Upper Limb Muscle Groups) in the Mean MAS Score for All Injected Upper Limb Muscle Groups From Treatment Cycle 2 Onwards TC 3: Wrist Flexors at Week 12 (n=2)	-1.5 units on a scale Standard Deviation 0.7	—	—

SECONDARY outcome

Timeframe: Weeks 4 and 12 of Treatment Cycles 1 to 3; Week 4 of Treatment Cycle 4.

Population: ITT population where n represents number of subjects with data. For Dysport 10 U/kg and 15 U/kg, the actual administered doses in the GSC of the (most) affected leg were \>7.5 to ≤12.5 U/kg and \>12.5 to ≤17.5 U/kg, respectively. The analysis excluded subjects with doses ≤7.5 or \>17.5 U/kg.

Global assessment of treatment response based on changes since the first injection in the DB study. PGA Scale of the Treatment Response: Global assessment of treatment response was assessed by asking the Investigator the following question: "how would you rate the response to treatment in the subject's lower limb(s) since the first injection in the DB study?" Answers were made on a 9 point rating scale (-4: markedly worse, -3: much worse, -2: worse, -1: slightly worse, 0: no change, +1: slightly improved, +2: improved, +3: much improved, +4: markedly improved).

Outcome measures

Measure	Total Dysport n=195 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Physician's Global Assessment (PGA) Score Treatment Cycle 1 at Week 12 (n=180)	1.0 units on a scale Standard Deviation 1.2	—	—
Mean Physician's Global Assessment (PGA) Score Treatment Cycle 2 at Week 4 (n=159)	1.5 units on a scale Standard Deviation 1.0	—	—
Mean Physician's Global Assessment (PGA) Score Treatment Cycle 2 at Week 12 (n=116)	0.9 units on a scale Standard Deviation 1.3	—	—
Mean Physician's Global Assessment (PGA) Score Treatment Cycle 3 at Week 4 (n=78)	1.4 units on a scale Standard Deviation 0.9	—	—
Mean Physician's Global Assessment (PGA) Score Treatment Cycle 3 at Week 12 (n=37)	0.7 units on a scale Standard Deviation 1.4	—	—
Mean Physician's Global Assessment (PGA) Score Treatment Cycle 1 at Week 4 (n=195)	1.5 units on a scale Standard Deviation 0.9	—	—
Mean Physician's Global Assessment (PGA) Score Treatment Cycle 4 at Week 4 (n=8)	0.5 units on a scale Standard Deviation 0.8	—	—

SECONDARY outcome

Timeframe: Weeks 4 and 12 of Treatment Cycles 1 to 3; Week 4 of Treatment Cycle 4

Population: ITT population where n represents number of subjects with data. For Dysport 10 U/kg and 15 U/kg, the actual administered doses in the GSC of the (most) affected leg were \>7.5 to ≤12.5 U/kg and \>12.5 to ≤17.5 U/kg, respectively. The analysis excluded subjects with doses ≤7.5 or \>17.5 U/kg.

Individual goals were defined prior to treatment in each treatment period. The GAS is a functional scale used to measure progress towards individual therapy goals. Individual goals were defined for each subject by the physician, and the child's parents (caregiver) where applicable, prior to treatment. After treatment in each treatment cycle, the GAS for each goal was rated using a defined scale (-2: Much less than expected outcome, -1: Somewhat less than expected outcome, 0: Expected outcome, 1: Somewhat more than expected outcome, and 2: Much more than expected outcome).

Outcome measures

Measure	Total Dysport n=194 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Goal Attainment Scale (GAS) Score Treatment Cycle 1 at Week 4 (n=194)	50.6 units on a scale Standard Deviation 11.0	—	—
Mean Goal Attainment Scale (GAS) Score Treatment Cycle 1 at Week 12 (n=178)	50.7 units on a scale Standard Deviation 10.1	—	—
Mean Goal Attainment Scale (GAS) Score Treatment Cycle 2 at Week 4 (n=158)	51.2 units on a scale Standard Deviation 11.0	—	—
Mean Goal Attainment Scale (GAS) Score Treatment Cycle 2 at Week 12 (n=116)	51.7 units on a scale Standard Deviation 10.5	—	—
Mean Goal Attainment Scale (GAS) Score Treatment Cycle 3 at Week 4 (n=78)	48.3 units on a scale Standard Deviation 10.7	—	—
Mean Goal Attainment Scale (GAS) Score Treatment Cycle 3 at Week 12 (n=36)	45.8 units on a scale Standard Deviation 8.9	—	—
Mean Goal Attainment Scale (GAS) Score Treatment Cycle 4 at Week 4 (n=8)	44.9 units on a scale Standard Deviation 9.4	—	—

SECONDARY outcome

Timeframe: DB baseline and Weeks 4 and 12 of Treatment Cycles 1 to 3; Week 4 of Treatment Cycle 4

Population: ITT population where n represents number of subjects with data. For Dysport 10 U/kg and 15 U/kg, the actual administered doses in the GSC of the (most) affected leg were \>7.5 to ≤12.5 U/kg and \>12.5 to ≤17.5 U/kg, respectively. The analysis excluded subjects with doses ≤7.5 or \>17.5 U/kg.

The TS was used to measure spasticity in the GSC at the ankle joint of the (most) affected lower limb.

The Investigator assessed muscle reactions of the tested muscle to passive stretch at two velocities: SLOW = V1: as slow as possible (slower than the rate of natural drop of the limb segment under gravity); FAST = V2 (speed of the limb segment falling under gravity) or V3 (as fast as possible - faster than the rate of natural drop of the limb segment under gravity).

The mean change from DB baseline in XV1 at slow speed was derived.

Outcome measures

Measure	Total Dysport n=169 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Change From DB Baseline in Angle of Arrest (XV1) Derived From the Tardieu Scale (TS), in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 4 at Week 4 (n=8)	-5.0 degrees Standard Deviation 9.6	—	—
Mean Change From DB Baseline in Angle of Arrest (XV1) Derived From the Tardieu Scale (TS), in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at Week 4 (n=169)	2.6 degrees Standard Deviation 9.0	—	—
Mean Change From DB Baseline in Angle of Arrest (XV1) Derived From the Tardieu Scale (TS), in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at Week 12 (n=156)	1.4 degrees Standard Deviation 9.2	—	—
Mean Change From DB Baseline in Angle of Arrest (XV1) Derived From the Tardieu Scale (TS), in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at Week 4 (n=121)	1.4 degrees Standard Deviation 9.2	—	—
Mean Change From DB Baseline in Angle of Arrest (XV1) Derived From the Tardieu Scale (TS), in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at Week 12 (n=92)	0.4 degrees Standard Deviation 10.9	—	—
Mean Change From DB Baseline in Angle of Arrest (XV1) Derived From the Tardieu Scale (TS), in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at Week 4 (n=66)	0.5 degrees Standard Deviation 10.1	—	—
Mean Change From DB Baseline in Angle of Arrest (XV1) Derived From the Tardieu Scale (TS), in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at Week 12 (n=35)	-1.1 degrees Standard Deviation 10.4	—	—

SECONDARY outcome

Timeframe: DB baseline and Weeks 4 and 12 of Treatment Cycles 1 to 3; Week 4 of Treatment Cycle 4

Population: ITT population where n represents number of subjects with data. For Dysport 10 U/kg and 15 U/kg, the actual administered doses in the GSC of the (most) affected leg were \>7.5 to ≤12.5 U/kg and \>12.5 to ≤17.5 U/kg, respectively. The analysis excluded subjects with doses ≤7.5 or \>17.5 U/kg.

The TS was used to measure spasticity in the GSC at the ankle joint of the (most) affected lower limb.

The Investigator assessed muscle reactions of the tested muscle to passive stretch at two velocities: SLOW = V1: as slow as possible (slower than the rate of natural drop of the limb segment under gravity); FAST = V2 (speed of the limb segment falling under gravity) or V3 (as fast as possible - faster than the rate of natural drop of the limb segment under gravity).

The mean change from DB baseline in XV3 at fast speed was derived.

Outcome measures

Measure	Total Dysport n=168 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Change From DB Baseline in Angle of Catch (XV3) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at Week 4 (n=168)	12.2 degrees Standard Deviation 13.7	—	—
Mean Change From DB Baseline in Angle of Catch (XV3) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at Week 12 (n=155)	9.9 degrees Standard Deviation 13.7	—	—
Mean Change From DB Baseline in Angle of Catch (XV3) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at Week 4 (n=119)	13.3 degrees Standard Deviation 12.6	—	—
Mean Change From DB Baseline in Angle of Catch (XV3) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at Week 12 (n=92)	11.4 degrees Standard Deviation 13.9	—	—
Mean Change From DB Baseline in Angle of Catch (XV3) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at Week 4 (n=65)	12.7 degrees Standard Deviation 13.4	—	—
Mean Change From DB Baseline in Angle of Catch (XV3) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at Week 12 (n=35)	9.9 degrees Standard Deviation 14.5	—	—
Mean Change From DB Baseline in Angle of Catch (XV3) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 4 at Week 4 (n=8)	4.4 degrees Standard Deviation 11.8	—	—

SECONDARY outcome

Timeframe: DB Baseline and Weeks 4 and 12 of Treatment Cycles 1 to 3; Week 4 of Treatment Cycle 4

Population: ITT population where n represents number of subjects with data. For Dysport 10 U/kg and 15 U/kg, the actual administered doses in the GSC of the (most) affected leg were \>7.5 to ≤12.5 U/kg and \>12.5 to ≤17.5 U/kg, respectively. The analysis excluded subjects with doses ≤7.5 or \>17.5 U/kg.

The TS was used to measure spasticity in the GSC at the ankle joint of the (most) affected lower limb.

The Investigator assessed muscle reactions of the tested muscle to passive stretch at two velocities: SLOW = V1: as slow as possible (slower than the rate of natural drop of the limb segment under gravity); FAST = V2 (speed of the limb segment falling under gravity) or V3 (as fast as possible - faster than the rate of natural drop of the limb segment under gravity).

X (threshold) was derived as XV1 at slow speed minus XV3 at fast speed and the mean change from DB baseline was calculated.

Outcome measures

Measure	Total Dysport n=168 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Change From DB Baseline in Spasticity Angle (X) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at Week 4 (n=168)	-9.7 degrees Standard Deviation 12.6	—	—
Mean Change From DB Baseline in Spasticity Angle (X) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at Week 12 (n=155)	-8.5 degrees Standard Deviation 11.9	—	—
Mean Change From DB Baseline in Spasticity Angle (X) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at Week 4 (n=119)	-12.0 degrees Standard Deviation 12.0	—	—
Mean Change From DB Baseline in Spasticity Angle (X) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at Week 12 (n=92)	-10.9 degrees Standard Deviation 12.8	—	—
Mean Change From DB Baseline in Spasticity Angle (X) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at Week 4 (n=65)	-12.2 degrees Standard Deviation 11.6	—	—
Mean Change From DB Baseline in Spasticity Angle (X) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at Week 12 (n=35)	-11.0 degrees Standard Deviation 13.4	—	—
Mean Change From DB Baseline in Spasticity Angle (X) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 4 at Week 4 (n=8)	-9.4 degrees Standard Deviation 8.6	—	—

SECONDARY outcome

Timeframe: DB Baseline and Weeks 4 and 12 of Treatment Cycles 1 to 3; Week 4 of Treatment Cycle 4

Population: ITT population where n represents number of subjects with data. For Dysport 10 U/kg and 15 U/kg, the actual administered doses in the GSC of the (most) affected leg were \>7.5 to ≤12.5 U/kg and \>12.5 to ≤17.5 U/kg, respectively. The analysis excluded subjects with doses ≤7.5 or \>17.5 U/kg.

The mean change from baseline (in the DB study) in Y was derived from the TS.

Y was graded according to the following scale: Grade 0 - no resistance throughout passive movement (best outcome); Grade 1 - slight resistance throughout passive movement; Grade 2 - clear catch at precise angle, interrupting passive movement, followed by release; Grade 3 - fatigable clonus (less than 10 sec when maintaining pressure) occurring at a precise angle, followed by release; Grade 4 - unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at a precise angle; Grade 5 - joint immovable (worst outcome).

Catch without release was graded 0 if XV1=XV3, 'unratable' spasticity otherwise; catch with 'minimal' release was graded 2 if XV3 was consistent and consistently less than XV1.

Angle 0 = position of minimal stretch of the tested muscle. For Grades 0 and 1, spasticity angle X = 0 by definition.

Outcome measures

Measure	Total Dysport n=169 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Change From DB Baseline in Spasticity Grade (Y) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at week 4 (n=169)	-0.4 degrees Standard Deviation 0.7	—	—
Mean Change From DB Baseline in Spasticity Grade (Y) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at week 12 (n=92)	-0.3 degrees Standard Deviation 0.6	—	—
Mean Change From DB Baseline in Spasticity Grade (Y) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at week 12 (n=155)	-0.3 degrees Standard Deviation 0.6	—	—
Mean Change From DB Baseline in Spasticity Grade (Y) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at week 4 (n=120)	-0.4 degrees Standard Deviation 0.7	—	—
Mean Change From DB Baseline in Spasticity Grade (Y) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at week 4 (n=66)	-0.4 degrees Standard Deviation 0.6	—	—
Mean Change From DB Baseline in Spasticity Grade (Y) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at week 12 (n=35)	-0.3 degrees Standard Deviation 0.6	—	—
Mean Change From DB Baseline in Spasticity Grade (Y) Derived From the TS, in the GSC Assessed at the Ankle Joint of the (Most) Affected Lower Limb Treatment Cycle 4 at week 4 (n=8)	-0.3 degrees Standard Deviation 0.5	—	—

SECONDARY outcome

Timeframe: Baseline and Weeks 4 and 12 of Treatment Cycles 1 to 3; Baseline and Week 4 of Treatment Cycle 4

Population: ITT population where n represents number of subjects with data. For Dysport 5 U/kg and 10 U/kg, the actual administered doses in the hamstring of the (most) affected leg were \>3 to ≤7.5 U/kg and \>7.5 to ≤12.5 U/kg, respectively. Analysis excluded subjects with doses ≤3 or \>12.5 U/kg. Only data from subjects injected in the hamstring are presented.

The TS was used to measure spasticity in the knee flexors at the knee joint of the (most) affected lower limb.

The Investigator assessed muscle reactions of the tested muscle to passive stretch at two velocities: SLOW = V1: as slow as possible (slower than the rate of natural drop of the limb segment under gravity); FAST = V2 (speed of the limb segment falling under gravity) or V3 (as fast as possible - faster than the rate of natural drop of the limb segment under gravity).

The mean change from baseline (prior to the first injection cycle in the hamstrings) in XV1 at slow speed was derived.

Outcome measures

Measure	Total Dysport n=33 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in XV1 Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at Week 4 (n=26)	3.2 degrees Standard Deviation 10.0	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in XV1 Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at Week 12 (n=24)	6.9 degrees Standard Deviation 10.4	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in XV1 Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at Week 4 (n=13)	3.8 degrees Standard Deviation 12.1	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in XV1 Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at Week 4 (n=33)	3.0 degrees Standard Deviation 11.4	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in XV1 Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at Week 12 (n=21)	5.5 degrees Standard Deviation 11.4	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in XV1 Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at Week 12 (n=5)	2.0 degrees Standard Deviation 7.6	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in XV1 Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 4 at Week 4 (n=2)	5.0 degrees Standard Deviation 7.1	—	—

SECONDARY outcome

Timeframe: Baseline and Weeks 4 and 12 of Treatment Cycles 1 to 3; Baseline and Week 4 of Treatment Cycle 4

Population: ITT population where n represents number of subjects with data. For Dysport 5 U/kg and 10 U/kg, the actual administered doses in the hamstring of the (most) affected leg were \>3 to ≤7.5 U/kg and \>7.5 to ≤12.5 U/kg, respectively. Analysis excluded subjects with doses ≤3 or \>12.5 U/kg. Only data from subjects injected in the hamstring are presented.

The TS was used to measure spasticity in the knee flexors at the knee joint of the (most) affected lower limb.

The Investigator assessed muscle reactions of the tested muscle to passive stretch at two velocities: SLOW = V1: as slow as possible (slower than the rate of natural drop of the limb segment under gravity); FAST = V2 (speed of the limb segment falling under gravity) or V3 (as fast as possible - faster than the rate of natural drop of the limb segment under gravity).

The mean change from baseline (prior to the first injection cycle in the hamstrings) in XV3 at fast speed was derived.

Outcome measures

Measure	Total Dysport n=33 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in XV3 Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at Week 12 (n=21)	12.4 degrees Standard Deviation 16.5	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in XV3 Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at Week 4 (n=26)	10.1 degrees Standard Deviation 14.8	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in XV3 Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at Week 12 (n=24)	13.3 degrees Standard Deviation 16.3	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in XV3 Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at Week 4 (n=33)	8.2 degrees Standard Deviation 15.1	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in XV3 Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at Week 4 (n=13)	11.9 degrees Standard Deviation 22.3	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in XV3 Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at Week 12 (n=5)	30.0 degrees Standard Deviation 24.5	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in XV3 Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 4 at Week 4 (n=2)	5.0 degrees Standard Deviation 7.1	—	—

SECONDARY outcome

Timeframe: Baseline and Weeks 4 and 12 of Treatment Cycles 1 to 3; Baseline and Week 4 of Treatment Cycle 4

Population: ITT population where n represents number of subjects with data. For Dysport 5 U/kg and 10 U/kg, the actual administered doses in the hamstring of the (most) affected leg were \>3 to ≤7.5 U/kg and \>7.5 to ≤12.5 U/kg, respectively. Analysis excluded subjects with doses ≤3 or \>12.5 U/kg. Only data from subjects injected in the hamstring are presented.

The TS was used to measure spasticity in the knee flexors at the knee joint of the (most) affected lower limb.

The Investigator assessed muscle reactions of the tested muscle to passive stretch at two velocities: SLOW = V1: as slow as possible (slower than the rate of natural drop of the limb segment under gravity); FAST = V2 (speed of the limb segment falling under gravity) or V3 (as fast as possible - faster than the rate of natural drop of the limb segment under gravity).

X (threshold) was derived as XV1 at slow speed minus XV3 at fast speed and the mean change from baseline (prior to the first injection cycle in the hamstrings) was calculated.

Outcome measures

Measure	Total Dysport n=33 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in X Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at Week 4 (n=26)	-6.9 degrees Standard Deviation 11.3	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in X Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at Week 12 (n=24)	-6.5 degrees Standard Deviation 11.8	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in X Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at Week 4 (n=33)	-5.2 degrees Standard Deviation 12.0	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in X Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at Week 12 (n=21)	-6.9 degrees Standard Deviation 11.8	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in X Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at Week 4 (n=13)	-8.1 degrees Standard Deviation 13.6	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in X Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at Week 12 (n=5)	-28.0 degrees Standard Deviation 20.8	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in X Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 4 at Week 4 (n=2)	0.0 degrees Standard Deviation 14.1	—	—

SECONDARY outcome

Timeframe: Baseline and Weeks 4 and 12 of Treatment Cycles 1 to 3; Baseline and Week 4 of Treatment Cycle 4

Population: ITT population where n represents number of subjects with data. For Dysport 5 U/kg and 10 U/kg, the actual administered doses in the hamstring of the (most) affected leg were \>3 to ≤7.5 U/kg and \>7.5 to ≤12.5 U/kg, respectively. Analysis excluded subjects with doses ≤3 or \>12.5 U/kg. Only data from subjects injected in the hamstring are presented.

The mean change from baseline (prior to the first injection cycle in the hamstrings) in Y was derived from the TS.

Y was graded according to the following scale: Grade 0 - no resistance throughout passive movement (best outcome); Grade 1 - slight resistance throughout passive movement; Grade 2 - clear catch at precise angle, interrupting passive movement, followed by release; Grade 3 - fatigable clonus (less than 10 sec when maintaining pressure) occurring at a precise angle, followed by release; Grade 4 - unfatigable clonus (more than 10 seconds when maintaining pressure) occurring at a precise angle; Grade 5 - joint immovable (worst outcome).

Catch without release was graded 0 if XV1=XV3, 'unratable' spasticity otherwise; catch with 'minimal' release was graded 2 if XV3 was consistent and consistently less than XV1.

Angle 0 = position of minimal stretch of the tested muscle. For Grades 0 and 1, spasticity angle X = 0 by definition.

Outcome measures

Measure	Total Dysport n=33 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in Y Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at Week 4 (n=26)	-0.1 degrees Standard Deviation 0.6	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in Y Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 1 at Week 12 (n=24)	-0.1 degrees Standard Deviation 0.5	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in Y Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at Week 4 (n=33)	0.0 degrees Standard Deviation 0.6	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in Y Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 2 at Week 12 (n=21)	-0.1 degrees Standard Deviation 0.6	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in Y Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at Week 4 (n=13)	-0.1 degrees Standard Deviation 0.3	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in Y Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 3 at Week 12 (n=5)	-0.4 degrees Standard Deviation 0.9	—	—
Mean Change From Baseline (Prior to the First Injection Cycle in the Hamstrings) in Y Derived From the TS, in the Knee Flexors Assessed at the Knee Joint of the (Most) Affected Lower Limb Treatment Cycle 4 at Week 4 (n=2)	0.0 degrees Standard Deviation 0.0	—	—

SECONDARY outcome

Timeframe: DB Baseline and Weeks 4 and 12 of Treatment Cycles 1 to 3; Week 4 of Treatment Cycle 4

Population: ITT population where n represents number of subjects with data. For Dysport 10 U/kg and 15 U/kg, the actual administered doses in the GSC of the (most) affected leg were \>7.5 to ≤12.5 U/kg and \>12.5 to ≤17.5 U/kg, respectively. The analysis excluded subjects with doses ≤7.5 or \>17.5 U/kg.

The OGS is a measurement tool used to objectively quantify positive and negative features (impairments) of the upper motor neurone syndrome. The OGS is useful when children are too young or insufficiently cooperative for instrumented gait analysis. It is based on the Physicians Rating Scale but has some modifications to improve its sensitivity to detect changes following administration of Botulinum Toxin Type A (BTX-A).

The OGS total score was calculated as the sum of the individual question scores for Questions 1 to 7, with the highest possible score being 20. The parameters collected were: knee position in midstance, initial foot contact, foot contact at midstance, timing of heel raise, hindfoot at midstance, base of support and gait assistive devices. Higher scores indicate better gait.

The mean change from baseline (in the DB study) in the OGS total score of the (most) affected leg was derived.

Outcome measures

Measure	Total Dysport n=178 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Change From DB Baseline in the Observational Gait Scale (OGS) Total Score of the (Most) Affected Leg Treatment Cycle 2 at Week 4 (n=142)	1.4 units on a scale Standard Deviation 3.0	—	—
Mean Change From DB Baseline in the Observational Gait Scale (OGS) Total Score of the (Most) Affected Leg Treatment Cycle 1 at Week 4 (n=178)	1.0 units on a scale Standard Deviation 3.0	—	—
Mean Change From DB Baseline in the Observational Gait Scale (OGS) Total Score of the (Most) Affected Leg Treatment Cycle 1 at Week 12 (n=166)	0.3 units on a scale Standard Deviation 2.8	—	—
Mean Change From DB Baseline in the Observational Gait Scale (OGS) Total Score of the (Most) Affected Leg Treatment Cycle 2 at Week 12 (n=104)	0.8 units on a scale Standard Deviation 2.8	—	—
Mean Change From DB Baseline in the Observational Gait Scale (OGS) Total Score of the (Most) Affected Leg Treatment Cycle 3 at Week 4 (n=70)	1.4 units on a scale Standard Deviation 3.2	—	—
Mean Change From DB Baseline in the Observational Gait Scale (OGS) Total Score of the (Most) Affected Leg Treatment Cycle 3 at Week 12 (n=35)	1.0 units on a scale Standard Deviation 2.6	—	—
Mean Change From DB Baseline in the Observational Gait Scale (OGS) Total Score of the (Most) Affected Leg Treatment Cycle 4 at Week 4 (n=8)	0.3 units on a scale Standard Deviation 3.8	—	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT population where n represents number of subjects with data. For Treatment Cycle 4, Week 12 was not included in the study design. Subjects who completed the study or withdrew were counted as missing at subsequent visits.

The PedsQL has a disease specific CP module that is relevant to the study population and complements the core modules.

The 35-item questionnaire encompassed 7 scales including (1) daily activities (2) school activities (3) movement and balance (4) pain and hurt (5) fatigue (6) eating activities and (7) speech and communication. A 5-point scale was utilised for parent proxy-report: 0 = never a problem; 1 = almost never a problem; 2 = sometimes a problem; 3 = often a problem; 4 = almost always a problem.

Each CP score was calculated as follows: (1) Individual item scores were reversed and transformed from a 0-4 scale to a 0-100 scale by assigning 0=100, 1=75, 2=50, 3=25 and 4=0; (2) Each scale score was calculated as the sum of the transformed individual item scores, divided by the number of non-missing items. Higher scores indicated better quality of life (fewer symptoms or problems).

A scale score was only calculated if at least 50% of the associated items were non-missing.

Outcome measures

Measure	Total Dysport n=179 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 n=120 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 n=39 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Change From DB Baseline in the PedsQL Score (CP Module Scores) at Each Study Visit Except Week 4 Movement and balance at Week 12 (n=179,n=120,n=39)	7.7 units on a scale Standard Deviation 21.0	8.9 units on a scale Standard Deviation 19.6	13.5 units on a scale Standard Deviation 19.3
Mean Change From DB Baseline in the PedsQL Score (CP Module Scores) at Each Study Visit Except Week 4 Fatigue at Week 12 (n=178, n=120, n=39)	4.7 units on a scale Standard Deviation 19.0	5.0 units on a scale Standard Deviation 18.4	9.0 units on a scale Standard Deviation 17.0
Mean Change From DB Baseline in the PedsQL Score (CP Module Scores) at Each Study Visit Except Week 4 School activities at Week 12 (n=103, n=71, n=26)	3.8 units on a scale Standard Deviation 24.5	5.1 units on a scale Standard Deviation 20.4	7.7 units on a scale Standard Deviation 14.5
Mean Change From DB Baseline in the PedsQL Score (CP Module Scores) at Each Study Visit Except Week 4 Daily activities at Week 12 (n=178, n=119, n=39)	6.9 units on a scale Standard Deviation 18.6	9.2 units on a scale Standard Deviation 20.8	14.4 units on a scale Standard Deviation 19.0
Mean Change From DB Baseline in the PedsQL Score (CP Module Scores) at Each Study Visit Except Week 4 Pain and hurt at Week 12 (n=179, n=120, n=39)	3.5 units on a scale Standard Deviation 17.9	4.5 units on a scale Standard Deviation 16.2	2.7 units on a scale Standard Deviation 21.3
Mean Change From DB Baseline in the PedsQL Score (CP Module Scores) at Each Study Visit Except Week 4 Eating activities at Week 12 (n=178, n=120, n=39)	2.0 units on a scale Standard Deviation 15.2	2.1 units on a scale Standard Deviation 14.9	2.7 units on a scale Standard Deviation 10.8
Mean Change From DB Baseline in the PedsQL Score (CP Module Scores) at Each Study Visit Except Week 4 Speech&Communication at week 12(n=103, n=72, n=26)	2.5 units on a scale Standard Deviation 17.4	2.3 units on a scale Standard Deviation 16.1	5.8 units on a scale Standard Deviation 16.5

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT population where n represents number of subjects with data. For Treatment Cycle 4, Week 12 was not included in the study design. Subjects who completed the study or withdrew were counted as missing at subsequent visits. PHS = pyschosocial health summary; W12 = Week 12.

The PedsQL is a validated quality of life questionnaire, designed for children from 2 to 18 years of age. The Generic Core Scale covers four multidimensional scales including physical, emotional, social and school aspects, with three summary scales of total scale score, physical health summary score and psychosocial health summary score.

Each generic core scale was calculated as follows: (1) Individual item scores were reversed and transformed from a 0-4 scale to a 0-100 scale by assigning 0=100, 1=75, 2=50, 3=25 and 4=0; (2) Each scale score was calculated as the sum of the transformed individual item scores, divided by the number of non-missing items. Higher scores indicated better quality of life (fewer symptoms or problems).

A scale score was only calculated if at least 50% of the associated items were non-missing.

Outcome measures

Measure	Total Dysport n=174 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.	Dysport Treatment Cycle 2 n=119 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs	Dysport Treatment Cycle 3 n=39 Participants Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs
Mean Change From DB Baseline in the PedsQL Score (Generic Core Scores) at Each Study Visit Except Week 4 Physical health summary (W12) (n=173, n=119, n=39)	7.8 units on a scale Standard Deviation 17.2	6.1 units on a scale Standard Deviation 20.9	8.0 units on a scale Standard Deviation 20.6
Mean Change From DB Baseline in the PedsQL Score (Generic Core Scores) at Each Study Visit Except Week 4 PHS (W12) (n=174, n=118, n=39)	4.1 units on a scale Standard Deviation 13.5	4.6 units on a scale Standard Deviation 13.8	8.9 units on a scale Standard Deviation 12.1
Mean Change From DB Baseline in the PedsQL Score (Generic Core Scores) at Each Study Visit Except Week 4 Total Scale (W12) (n=173, n=119, n=39)	5.5 units on a scale Standard Deviation 12.5	5.2 units on a scale Standard Deviation 13.9	8.6 units on a scale Standard Deviation 13.6

Adverse Events

Total Dysport

Serious events: 7 serious events

Other events: 147 other events

Deaths: 0 deaths

Serious adverse events

Measure	Total Dysport n=215 participants at risk Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.
Respiratory, thoracic and mediastinal disorders Adenoidal hypertrophy	0.47% 1/215 • Number of events 1 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Blood and lymphatic system disorders Lymphadenopathy	0.47% 1/215 • Number of events 1 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Nervous system disorders Status Epilepticus	0.47% 1/215 • Number of events 2 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Nervous system disorders Complex Partial Seizures	0.47% 1/215 • Number of events 1 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Nervous system disorders Partial Seizures	0.47% 1/215 • Number of events 1 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Infections and infestations Pneumonia	0.93% 2/215 • Number of events 2 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Infections and infestations Sinusitis	0.47% 1/215 • Number of events 1 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Infections and infestations Varicella	0.47% 1/215 • Number of events 1 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Infections and infestations Gastroenteritis	0.47% 1/215 • Number of events 1 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.

Other adverse events

Measure	Total Dysport n=215 participants at risk Dysport was injected into the affected GSC with / without Hamstring injections at doses ranging between 5 U/kg to 20 U/kg for one leg and 10 U/kg to 30 U/kg for both legs.
Respiratory, thoracic and mediastinal disorders Cough	9.3% 20/215 • Number of events 24 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
General disorders Pyrexia	15.8% 34/215 • Number of events 43 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Gastrointestinal disorders Diarrhoea	7.4% 16/215 • Number of events 18 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Gastrointestinal disorders Vomiting	5.6% 12/215 • Number of events 15 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 12/215 • Number of events 13 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Infections and infestations Upper Respiratory Tract Infection	21.4% 46/215 • Number of events 71 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Infections and infestations Nasopharyngitis	21.9% 47/215 • Number of events 65 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Infections and infestations Influenza	9.3% 20/215 • Number of events 28 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Infections and infestations Pharyngitis	11.6% 25/215 • Number of events 32 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Infections and infestations Bronchitis	8.8% 19/215 • Number of events 23 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.
Infections and infestations Varicella	5.6% 12/215 • Number of events 12 • From Day 1 to end of study (week 40) Safety population. One subject received placebo in the DB study and two cycles of Dysport in the OL study. As both Dysport treatments were outside of the ranges specified (≤7.5 U/kg in Treatment Cycles 1 and 2), the subject was excluded from the analysis (no TEAEs were reported for this subject), and the number of participants at risk was equal to 215. A total of 175 subjects experienced nonserious AEs, of whom 147 experienced nonserious AEs that occurred above the frequency threshold of 5%.

Additional Information

Medical Director, Neurology

Ipsen

Phone: clinical.trials@ipsen.com

Email: clinical.trials@ipsen.com

Results disclosure agreements

• Principal investigator is a sponsor employee A plan for scientific publication and presentation of the results could be agreed and implemented by the study investigators or a steering committee. The sponsor required that reasonable opportunity be given to review the content and conclusions of any abstract, presentation, or paper before the material was submitted for publication or communicated. This condition also applied to any amendments that were subsequently requested by referees or journal editors.
• Publication restrictions are in place

Restriction type: OTHER