Trial Outcomes & Findings for Dysport® Pediatric Lower Limb Spasticity Study (NCT NCT01249417)

Last Updated: 2022-09-28

Results Overview

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. Investigator will grade muscle tone in the GSC from 0 (no increase in tone) to 4 (affected parts rigid in flexion or extension).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

241 participants

Primary outcome timeframe

Change from baseline to Week 4

Results posted on

2022-09-28

Participant Flow

Each centre that participated in the study was expected to randomise between five and 25 subjects. It was planned to have at least two participating centres per country.

Screening details: A total of 241 subjects were randomised to the study. The safety population included 239 subjects who were treated. Out of the 239 treated subjects, 4 subjects were excluded from the Intent-to-Treat (ITT) population because no MAS score was obtained at the baseline visit and/or at Week 4.

Participant milestones

Participant milestones
Measure	Dysport 10 U/Kg 10 U/Kg per lower limb. Either one or both lower limbs can be treated. Total volume injected, 2ml per leg. Botulinum type A toxin (Dysport®): I.M. (in the muscle) injection on day 1 of a single treatment cycle.	Dysport 15 U/Kg 15 U/Kg per lower limb. Either one or both lower limbs can be treated. Total volume injected, 2ml per leg. Botulinum type A toxin (Dysport®): I.M. (in the muscle) injection on day 1 of a single treatment cycle.	Placebo Total volume to be injected per lower limb - 2ml. Either one or both lower limbs can be treated. Placebo: I.M. injection on day 1 of a single treatment cycle.
Randomised Population STARTED	80	80	81
Randomised Population Treated	80	80	79
Randomised Population COMPLETED	79	79	77
Randomised Population NOT COMPLETED	1	1	4
Treatment Phase - ITT Population STARTED	79	79	77
Treatment Phase - ITT Population COMPLETED	78	75	73
Treatment Phase - ITT Population NOT COMPLETED	1	4	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Dysport 10 U/Kg 10 U/Kg per lower limb. Either one or both lower limbs can be treated. Total volume injected, 2ml per leg. Botulinum type A toxin (Dysport®): I.M. (in the muscle) injection on day 1 of a single treatment cycle.	Dysport 15 U/Kg 15 U/Kg per lower limb. Either one or both lower limbs can be treated. Total volume injected, 2ml per leg. Botulinum type A toxin (Dysport®): I.M. (in the muscle) injection on day 1 of a single treatment cycle.	Placebo Total volume to be injected per lower limb - 2ml. Either one or both lower limbs can be treated. Placebo: I.M. injection on day 1 of a single treatment cycle.
Randomised Population Study treatment not received	0	0	2
Randomised Population No MAS score at baseline and/or Week 4	1	1	2
Treatment Phase - ITT Population Other	0	0	1
Treatment Phase - ITT Population Adverse Event	0	0	1
Treatment Phase - ITT Population Withdrawal by Subject	1	3	1
Treatment Phase - ITT Population Lost to Follow-up	0	1	1

Baseline Characteristics

Dysport® Pediatric Lower Limb Spasticity Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dysport 10 U/Kg n=79 Participants Dysport 10 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.	Dysport 15 U/Kg n=79 Participants Dysport 15 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.	Placebo n=77 Participants Placebo intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.	Total n=235 Participants Total of all reporting groups
Age, Continuous	6 years STANDARD_DEVIATION 3.3 • n=5 Participants	5.7 years STANDARD_DEVIATION 3.2 • n=7 Participants	5.9 years STANDARD_DEVIATION 3.5 • n=5 Participants	5.9 years STANDARD_DEVIATION 3.3 • n=4 Participants
Age, Customized Children (2-9 years)	67 participants n=5 Participants	67 participants n=7 Participants	65 participants n=5 Participants	199 participants n=4 Participants
Age, Customized Children (10-17 years)	12 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants	36 participants n=4 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	48 Participants n=7 Participants	48 Participants n=5 Participants	141 Participants n=4 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	31 Participants n=7 Participants	29 Participants n=5 Participants	94 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	21 Participants n=5 Participants	21 Participants n=7 Participants	20 Participants n=5 Participants	62 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	58 Participants n=5 Participants	58 Participants n=7 Participants	57 Participants n=5 Participants	173 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Black/African American	2 participants n=5 Participants	0 participants n=7 Participants	5 participants n=5 Participants	7 participants n=4 Participants
Race/Ethnicity, Customized Caucasian/White	57 participants n=5 Participants	60 participants n=7 Participants	55 participants n=5 Participants	172 participants n=4 Participants
Race/Ethnicity, Customized American Indian/Alaskan Native	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Multiple	19 participants n=5 Participants	19 participants n=7 Participants	17 participants n=5 Participants	55 participants n=4 Participants
Botulinum toxin Status Naive	40 participants n=5 Participants	41 participants n=7 Participants	41 participants n=5 Participants	122 participants n=4 Participants
Botulinum toxin Status Non-naive	39 participants n=5 Participants	38 participants n=7 Participants	36 participants n=5 Participants	113 participants n=4 Participants
Number of legs being treated 1 Leg injected	42 participants n=5 Participants	50 participants n=7 Participants	47 participants n=5 Participants	139 participants n=4 Participants
Number of legs being treated 2 Legs injected	37 participants n=5 Participants	29 participants n=7 Participants	30 participants n=5 Participants	96 participants n=4 Participants
Gross Motor Function Classification System (GMFCS) GMFCS level 1	46 participants n=5 Participants	45 participants n=7 Participants	40 participants n=5 Participants	131 participants n=4 Participants
Gross Motor Function Classification System (GMFCS) GMFCS level 2	24 participants n=5 Participants	24 participants n=7 Participants	30 participants n=5 Participants	78 participants n=4 Participants
Gross Motor Function Classification System (GMFCS) GMFCS level 3	9 participants n=5 Participants	10 participants n=7 Participants	7 participants n=5 Participants	26 participants n=4 Participants
Height	117.1 cm STANDARD_DEVIATION 20.7 • n=5 Participants	111.6 cm STANDARD_DEVIATION 18.5 • n=7 Participants	114.6 cm STANDARD_DEVIATION 19.7 • n=5 Participants	114.4 cm STANDARD_DEVIATION 19.7 • n=4 Participants
Weight	23.1 kg STANDARD_DEVIATION 13.4 • n=5 Participants	21.1 kg STANDARD_DEVIATION 10.7 • n=7 Participants	22.6 kg STANDARD_DEVIATION 11.9 • n=5 Participants	22.3 kg STANDARD_DEVIATION 12.0 • n=4 Participants
Body Mass Index (BMI)	15.8 kg/m2 STANDARD_DEVIATION 2.9 • n=5 Participants	16.1 kg/m2 STANDARD_DEVIATION 2.7 • n=7 Participants	16.2 kg/m2 STANDARD_DEVIATION 2.7 • n=5 Participants	16.0 kg/m2 STANDARD_DEVIATION 2.8 • n=4 Participants
Modified Ashworth Scale (MAS) score	3.1 units on a scale STANDARD_DEVIATION 0.3 • n=5 Participants	3.1 units on a scale STANDARD_DEVIATION 0.3 • n=7 Participants	3.2 units on a scale STANDARD_DEVIATION 0.4 • n=5 Participants	3.1 units on a scale STANDARD_DEVIATION 0.4 • n=4 Participants

PRIMARY outcome

Timeframe: Change from baseline to Week 4

Population: ITT population, defined as all randomised subjects who received at least one injection of study treatment and who had a MAS score in the GSC assessed both at baseline and at Week 4.

Outcome measures

Outcome measures
Measure	Dysport 10 U/Kg n=79 Participants Dysport 10 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.	Dysport 15 U/Kg n=79 Participants Dysport 15 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.	Placebo n=77 Participants Placebo intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.
Change in MAS Score in the Gastrocnemius-soleus Complex (GSC) at the Ankle Joint of the (Most) Affected Lower Limb	-0.86 units on a scale Interval -1.07 to -0.65	-0.97 units on a scale Interval -1.18 to -0.76	-0.48 units on a scale Interval -0.69 to -0.27

SECONDARY outcome

Timeframe: Week 4

Population: ITT population, defined as all randomised subjects who received at least one injection of study treatment and who had a MAS score in the GSC assessed both at baseline and at Week 4.

PGA Scale of the Treatment Response: Global assessment of treatment response 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 last injection?" Answers will be 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

Outcome measures
Measure	Dysport 10 U/Kg n=79 Participants Dysport 10 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.	Dysport 15 U/Kg n=79 Participants Dysport 15 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.	Placebo n=77 Participants Placebo intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.
Physician's Global Assessment (PGA) of the Treatment Response.	1.54 units on a scale Interval 1.28 to 1.81	1.5 units on a scale Interval 1.23 to 1.77	0.73 units on a scale Interval 0.46 to 0.99

SECONDARY outcome

Timeframe: Week 4

Population: ITT population, defined as all randomised subjects who received at least one injection of study treatment and who had a MAS score in the GSC assessed both at baseline and at Week 4.

GAS is a functional scale used to measure progress towards individual therapy goals. Individual goals defined for each subject by the physician, and the child's parents (caregiver) where applicable, prior to treatment. Post-baseline, the GAS for each goal 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

Outcome measures
Measure	Dysport 10 U/Kg n=79 Participants Dysport 10 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.	Dysport 15 U/Kg n=79 Participants Dysport 15 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.	Placebo n=77 Participants Placebo intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.
Goal Attainment Scale (GAS) Score	51.53 units on a scale Interval 49.05 to 54.01	50.86 units on a scale Interval 48.36 to 53.36	46.21 units on a scale Interval 43.7 to 48.72

Adverse Events

Dysport 10 U/Kg

Serious events: 1 serious events

Other events: 51 other events

Deaths: 0 deaths

Dysport 15 U/Kg

Serious events: 0 serious events

Other events: 51 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dysport 10 U/Kg n=80 participants at risk Dysport 10 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.	Dysport 15 U/Kg n=80 participants at risk Dysport 15 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.	Placebo n=79 participants at risk Placebo intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.
Injury, poisoning and procedural complications Head injury	0.00% 0/80 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).	0.00% 0/80 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).	1.3% 1/79 • Number of events 1 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/80 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).	0.00% 0/80 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).	1.3% 1/79 • Number of events 1 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).
Respiratory, thoracic and mediastinal disorders Adenoidal hypertrophy	1.2% 1/80 • Number of events 1 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).	0.00% 0/80 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).	0.00% 0/79 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).
Respiratory, thoracic and mediastinal disorders Gastroenteritis	0.00% 0/80 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).	0.00% 0/80 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).	1.3% 1/79 • Number of events 1 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).
Infections and infestations Pneumonia	0.00% 0/80 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).	0.00% 0/80 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).	1.3% 1/79 • Number of events 1 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).
Infections and infestations Rotavirus infection	0.00% 0/80 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).	0.00% 0/80 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).	1.3% 1/79 • Number of events 1 • Up to Week 28 of follow-up The safety population, defined as all randomised subjects who received at least one injection of study treatment, was used for the analysis of adverse events (AEs).

Other adverse events

Additional Information

Medical Director, Neurology

Ipsen

Phone: [email protected]

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place