ClinicalTrials.gov
ClinicalTrials.gov Menu

Dysport® Pediatric Lower Limb Spasticity Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01249417
Recruitment Status : Completed
First Posted : November 29, 2010
Results First Posted : February 3, 2017
Last Update Posted : February 3, 2017
Sponsor:
Information provided by (Responsible Party):
Ipsen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Cerebral Palsy
Muscle Spasticity
Children
Interventions Drug: Botulinum type A toxin (Dysport®)
Drug: Placebo
Enrollment 241
Recruitment Details 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.
Pre-assignment Details

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.

Arm/Group Title Dysport 10 U/Kg Dysport 15 U/Kg Placebo
Hide Arm/Group Description

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.

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.

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.

Period Title: Randomised Population
Started 80 80 81
Treated [1] 80 80 79
Completed 79 79 77
Not Completed 1 1 4
Reason Not Completed
Study treatment not received             0             0             2
No MAS score at baseline and/or Week 4             1             1             2
[1]
Constitutes the safety population.
Period Title: Treatment Phase - ITT Population
Started 79 79 77
Completed 78 75 73
Not Completed 1 4 4
Reason Not Completed
Not specified             0             0             1
Adverse Event             0             0             1
Withdrawal by Subject             1             3             1
Lost to Follow-up             0             1             1
Arm/Group Title Dysport 10 U/Kg Dysport 15 U/Kg Placebo Total
Hide Arm/Group Description Dysport 10 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment. Dysport 15 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment. Placebo intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment. Total of all reporting groups
Overall Number of Baseline Participants 79 79 77 235
Hide Baseline Analysis Population Description
Baseline characteristic values were based on the 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.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 79 participants 79 participants 77 participants 235 participants
6  (3.3) 5.7  (3.2) 5.9  (3.5) 5.9  (3.3)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 79 participants 79 participants 77 participants 235 participants
Children (2-9 years) 67 67 65 199
Children (10-17 years) 12 12 12 36
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 79 participants 77 participants 235 participants
Female
45
  57.0%
48
  60.8%
48
  62.3%
141
  60.0%
Male
34
  43.0%
31
  39.2%
29
  37.7%
94
  40.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 79 participants 77 participants 235 participants
Hispanic or Latino
21
  26.6%
21
  26.6%
20
  26.0%
62
  26.4%
Not Hispanic or Latino
58
  73.4%
58
  73.4%
57
  74.0%
173
  73.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 79 participants 79 participants 77 participants 235 participants
Black/African American 2 0 5 7
Caucasian/White 57 60 55 172
American Indian/Alaskan Native 1 0 0 1
Multiple 19 19 17 55
Botulinum toxin Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 79 participants 79 participants 77 participants 235 participants
Naive 40 41 41 122
Non-naive 39 38 36 113
Number of legs being treated  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 79 participants 79 participants 77 participants 235 participants
1 Leg injected 42 50 47 139
2 Legs injected 37 29 30 96
Gross Motor Function Classification System (GMFCS)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 79 participants 79 participants 77 participants 235 participants
GMFCS level 1 46 45 40 131
GMFCS level 2 24 24 30 78
GMFCS level 3 9 10 7 26
[1]
Measure Description: Participants were staged according to the following GMFCS criteria: level 1 (walks without limitations (best outcome)), level 2 (walks with limitations) and level 3 (walks using a hand held mobility device (worst outcome)). Only participants classified as GMFCS levels 1 to 3 were eligible for entry into the study.
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 79 participants 79 participants 77 participants 235 participants
117.1  (20.7) 111.6  (18.5) 114.6  (19.7) 114.4  (19.7)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 79 participants 79 participants 77 participants 235 participants
23.1  (13.4) 21.1  (10.7) 22.6  (11.9) 22.3  (12.0)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m2
Number Analyzed 79 participants 79 participants 77 participants 235 participants
15.8  (2.9) 16.1  (2.7) 16.2  (2.7) 16.0  (2.8)
Modified Ashworth Scale (MAS) score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 79 participants 79 participants 77 participants 235 participants
3.1  (0.3) 3.1  (0.3) 3.2  (0.4) 3.1  (0.4)
[1]
Measure Description: 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 gastrocnemius-soleus complex (GSC) from 0 (no increase in tone) to 4 (affected parts rigid in flexion or extension).
1.Primary Outcome
Title Change in MAS Score in the Gastrocnemius-soleus Complex (GSC) at the Ankle Joint of the (Most) Affected Lower Limb
Hide Description 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).
Time Frame Change from baseline to Week 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Dysport 10 U/Kg Dysport 15 U/Kg Placebo
Hide Arm/Group Description:
Dysport 10 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.
Dysport 15 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.
Placebo intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.
Overall Number of Participants Analyzed 79 79 77
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-0.86
(-1.07 to -0.65)
-0.97
(-1.18 to -0.76)
-0.48
(-0.69 to -0.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dysport 10 U/Kg, Placebo
Comments LS means for each treatment group and treatment comparisons, as well as the p-values were obtained from an ANCOVA on the change from baseline with treatment, baseline MAS score, age range at baseline, BTX status at baseline and centre as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0029
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.64 to -0.13
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dysport 15 U/Kg, Placebo
Comments LS means for each treatment group and treatment comparisons, as well as the p-values were obtained from an ANCOVA on the change from baseline with treatment, baseline MAS score, age range at baseline, BTX status at baseline and centre as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -0.49
Confidence Interval (2-Sided) 95%
-0.75 to -0.23
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Physician’s Global Assessment (PGA) of the Treatment Response.
Hide Description 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).
Time Frame Week 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Dysport 10 U/Kg Dysport 15 U/Kg Placebo
Hide Arm/Group Description:
Dysport 10 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.
Dysport 15 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.
Placebo intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.
Overall Number of Participants Analyzed 79 79 77
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
1.54
(1.28 to 1.81)
1.5
(1.23 to 1.77)
0.73
(0.46 to 0.99)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dysport 10 U/Kg, Placebo
Comments LS means for each treatment group and treatment comparisons, as well as the p-values were obtained from an ANOVA on the visit value with treatment, age range at baseline, BTX status at baseline and centre as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.50 to 1.14
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dysport 15 U/Kg, Placebo
Comments LS means for each treatment group and treatment comparisons, as well as the p-values were obtained from an ANOVA on the visit value with treatment, age range at baseline, BTX status at baseline and centre as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.45 to 1.10
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Goal Attainment Scale (GAS) Score
Hide Description 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).
Time Frame Week 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Dysport 10 U/Kg Dysport 15 U/Kg Placebo
Hide Arm/Group Description:
Dysport 10 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.
Dysport 15 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.
Placebo intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.
Overall Number of Participants Analyzed 79 79 77
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
51.53
(49.05 to 54.01)
50.86
(48.36 to 53.36)
46.21
(43.7 to 48.72)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dysport 10 U/Kg, Placebo
Comments LS means for each treatment group and treatment comparisons, as well as the p-values were obtained from an ANOVA on the visit value with treatment, age range at baseline, BTX status at baseline and centre as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 5.32
Confidence Interval (2-Sided) 95%
2.31 to 8.32
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Dysport 15 U/Kg, Placebo
Comments LS means for each treatment group and treatment comparisons, as well as the p-values were obtained from an ANOVA on the visit value with treatment, age range at baseline, BTX status at baseline and centre as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0031
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 4.65
Confidence Interval (2-Sided) 95%
1.59 to 7.71
Estimation Comments [Not Specified]
Time Frame Up to Week 28 of follow-up
Adverse Event Reporting Description 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).
 
Arm/Group Title Dysport 10 U/Kg Dysport 15 U/Kg Placebo
Hide Arm/Group Description Dysport 10 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment. Dysport 15 U/Kg intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment. Placebo intramuscular injection on either one or both lower limbs (2 ml per leg), single treatment.
All-Cause Mortality
Dysport 10 U/Kg Dysport 15 U/Kg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Dysport 10 U/Kg Dysport 15 U/Kg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/80 (1.25%)      0/80 (0.00%)      4/79 (5.06%)    
Infections and infestations       
Pneumonia  1  0/80 (0.00%)  0 0/80 (0.00%)  0 1/79 (1.27%)  1
Rotavirus infection  1  0/80 (0.00%)  0 0/80 (0.00%)  0 1/79 (1.27%)  1
Injury, poisoning and procedural complications       
Head injury  1  0/80 (0.00%)  0 0/80 (0.00%)  0 1/79 (1.27%)  1
Upper limb fracture  1  0/80 (0.00%)  0 0/80 (0.00%)  0 1/79 (1.27%)  1
Respiratory, thoracic and mediastinal disorders       
Adenoidal hypertrophy  1  1/80 (1.25%)  1 0/80 (0.00%)  0 0/79 (0.00%)  0
Gastroenteritis  1  0/80 (0.00%)  0 0/80 (0.00%)  0 1/79 (1.27%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Dysport 10 U/Kg Dysport 15 U/Kg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   51/80 (63.75%)      51/80 (63.75%)      42/79 (53.16%)    
Gastrointestinal disorders       
Vomiting  1  3/80 (3.75%)  3 4/80 (5.00%)  5 4/79 (5.06%)  4
Diarrhoea  1  2/80 (2.50%)  2 2/80 (2.50%)  2 1/79 (1.27%)  1
Nausea  1  2/80 (2.50%)  3 1/80 (1.25%)  3 1/79 (1.27%)  2
Abdominal pain upper  1  1/80 (1.25%)  1 0/80 (0.00%)  0 2/79 (2.53%)  2
Abdominal pain  1  0/80 (0.00%)  0 0/80 (0.00%)  0 2/79 (2.53%)  2
General disorders       
Pyrexia  1  6/80 (7.50%)  7 8/80 (10.00%)  8 4/79 (5.06%)  4
Infections and infestations       
Upper respiratory tract infection  1  6/80 (7.50%)  8 13/80 (16.25%)  15 10/79 (12.66%)  11
Nasopharyngitis  1  10/80 (12.50%)  13 9/80 (11.25%)  10 4/79 (5.06%)  8
Influenza  1  5/80 (6.25%)  6 6/80 (7.50%)  9 6/79 (7.59%)  7
Bronchitis  1  3/80 (3.75%)  4 2/80 (2.50%)  2 2/79 (2.53%)  2
Gastroenteritis viral  1  1/80 (1.25%)  1 2/80 (2.50%)  2 0/79 (0.00%)  0
Ear infection  1  0/80 (0.00%)  0 2/80 (2.50%)  4 2/79 (2.53%)  2
Upper respiratory tract infection bacterial  1  0/80 (0.00%)  0 2/80 (2.50%)  2 0/79 (0.00%)  0
Pharyngitis  1  6/80 (7.50%)  7 1/80 (1.25%)  1 3/79 (3.80%)  3
Rhinitis  1  3/80 (3.75%)  3 1/80 (1.25%)  1 3/79 (3.80%)  3
Urinary tract infection  1  2/80 (2.50%)  2 1/80 (1.25%)  1 3/79 (3.80%)  3
Respiratory tract infection viral  1  2/80 (2.50%)  2 1/80 (1.25%)  1 0/79 (0.00%)  0
Viral infection  1  1/80 (1.25%)  1 1/80 (1.25%)  2 4/79 (5.06%)  5
Varicella  1  4/80 (5.00%)  4 0/80 (0.00%)  0 1/79 (1.27%)  1
Injury, poisoning and procedural complications       
Excoriation  1  2/80 (2.50%)  2 0/80 (0.00%)  0 0/79 (0.00%)  0
Fall  1  1/80 (1.25%)  1 0/80 (0.00%)  0 2/79 (2.53%)  2
Musculoskeletal and connective tissue disorders       
Pain in extremity  1  2/80 (2.50%)  2 3/80 (3.75%)  3 4/79 (5.06%)  4
Muscular weakness  1  2/80 (2.50%)  2 0/80 (0.00%)  0 1/79 (1.27%)  1
Nervous system disorders       
Epilepsy  1  2/80 (2.50%)  3 3/80 (3.75%)  4 0/79 (0.00%)  0
Headache  1  0/80 (0.00%)  0 2/80 (2.50%)  3 1/79 (1.27%)  1
Respiratory, thoracic and mediastinal disorders       
Cough  1  8/80 (10.00%)  10 6/80 (7.50%)  6 5/79 (6.33%)  5
Oropharyngeal pain  1  1/80 (1.25%)  1 2/80 (2.50%)  2 0/79 (0.00%)  0
Rhinorrhea  1  1/80 (1.25%)  1 0/80 (0.00%)  0 2/79 (2.53%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Medical Director, Neurology
Organization: Ipsen
Phone: clinical.trials@ipsen.com
Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT01249417     History of Changes
Other Study ID Numbers: Y-55-52120-141
2009-017709-12 ( EudraCT Number )
First Submitted: November 25, 2010
First Posted: November 29, 2010
Results First Submitted: August 30, 2016
Results First Posted: February 3, 2017
Last Update Posted: February 3, 2017