Cervical Dystonia
Conditions
Brief summary
The purpose of this study is to evaluate how well a new drug called Dysport NG works and how safe it is, when it is used for the treatment of cervical dystonia. Dysport NG will be compared to an approved drug called Dysport.
Detailed description
The primary study objectives will be assessed in terms of improvement of the subject's CD at a pre-defined time point after treatment. The primary study objectives are to demonstrate the superiority of Dysport NG to placebo in terms of efficacy and to test the non-inferior efficacy of Dysport NG, when compared to Dysport, in CD subjects. In addition to testing for the primary study objectives, the superiority in terms of efficacy of Dysport versus placebo, will be assessed. This clinical study was designed and implemented and reported in accordance with the International Conference on Harmonization (ICH) Harmonized Tripartite Guidelines for Good Clinical Practice (GCP), with applicable local regulations (including European Directive 2001/20/EC, US Code of Federal Regulations Title 21, and with the ethical principles laid down in the Declaration of Helsinki. A large body of evidence demonstrates the safety and efficacy of Dysport across several clinical indications. This study was the first use of Dysport NG in humans with CD. The active substance (BTX-A-HAC) in Dysport NG was the same as in the currently marketed Dysport product and had the same mechanism of action. Dysport NG was, therefore, expected to have the same efficacy and safety profile in humans as Dysport, with the advantage of eliminating the potential risk of transmission of infective agents, by the substitution of plant and synthetic products for human and animal-derived products. However, due to the change of excipient, thorough assessment of the safety and efficacy of Dysport NG is necessary. Previous clinical studies indicate that the maximum effect of Dysport and maximum improvements in CD are observed approximately 4 weeks post treatment, after which there is a gradual return to baseline disease status. The Week 4 follow up visit after the first treatment cycle was therefore, chosen as the primary time point of interest. Retreatment is necessary in order to maintain the beneficial effect and the long term treatment of CD. Previously conducted long term studies demonstrate the maintenance of the therapeutic effect of Dysport following repeated treatments, with a favourable short and long term safety and immunogenicity profile.
Interventions
BIOLOGICALBotulinum toxin type A
I.M. (in the muscle) injection on day 1 of up to 5 treatment cycles.
DRUGPlacebo
I.M. injection on day 1 of treatment cycle 1.
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Dystonia with at least 18 months duration since onset. * Previously untreated with Botulinum toxin-A (BTX-A) or -B or a minimum of 14 weeks since the last injection. * TWSTRS score at baseline of: Total score ≥ 30, Severity Sub-Scale score ≥ 15, Disability Sub-Scale score ≥ 3, Pain Sub-Scale score ≥ 2.
Exclusion criteria
* Known hypersensitivity to Botulinum toxin (BTX) or related compounds or any component in the study drug formulation (including cow milk protein). * Pure anterocollis or pure retrocollis. * In apparent remission from Cervical Dystonia. * Known clinically significant underlying swallowing or respiratory abnormality which might be exacerbated by BTX treatment. * Previous poor response to BTX treatment or known presence of BTX neutralising antibodies. * Previous phenol or alcohol injections into the neck muscles. * Previous myotomy or denervation surgery involving the neck or shoulder region.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score Following First Treatment Cycle | Baseline and Week 4 | TWSTRS measures the degree of CD and is comprised of three different components, namely Severity, Disability and Pain subscales. There is an ordinal scale score and range for each component. Severity scores range from 0 (absence of severity) to 35 (maximum severity), Disability scores range from 0 (no disability) to 30 (maximum disability) and Pain scores range from 0 (no pain) to 20 (maximum pain). TWSTRS Total score is the sum of the 3 component scores ranging from 0 to a maximum of 85, with higher scores denoting worse outcome. If the change from baseline is negative, this represents an improvement in symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Subscale Score Following First Treatment Cycle | Baseline and Week 4 | TWSTRS measures the degree of CD and comprises three different components, one of which is the Disability subscale. TWSTRS Disability subscale scores range from 0 (no disability) to 30 (maximum disability). If the change from baseline is negative, this represents an improvement in symptoms. |
| Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Subscale Score Following First Treatment Cycle | Baseline and Week 4 | TWSTRS measures the degree of CD and comprises three different components, one of which is the Pain subscale. TWSTRS Pain subscale scores range from 0 (no pain) to 20 (maximum pain). If the change from baseline is negative, this represents an improvement in symptoms. |
| Change From Baseline in Subject Visual Analogue Score (VAS) for Pain From Cervical Dystonia Following First Treatment Cycle | Baseline and Week 4 | The assessment was made on a continuous 100-mm horizontal line with a scale range of 0 mm (no pain) to 100 mm (worst possible pain). |
| Change From Baseline in Subject Visual Analogue Score (VAS) for Symptoms of Cervical Dystonia Following First Treatment Cycle | Baseline and Week 4 | The assessment was made on a continuous 100-mm horizontal line with a scale range of 0 mm (no symptoms) to 100 mm (worst possible symptoms). |
| Percentage of Treatment Responders Following First Treatment Cycle | Baseline and Week 4 | A treatment responder was defined as a patient with \>30% improvement in TWSTRS Total score compared to baseline. TWSTRS measures the degree of CD and is comprised of three different components, namely Severity, Disability and Pain subscales. There is an ordinal scale score and range for each component. Severity scores range from 0 (absence of severity) to 35 (maximum severity), Disability scores range from 0 (no disability) to 30 (maximum disability) and Pain scores range from 0 (no pain) to 20 (maximum pain). TWSTRS Total score is the sum of the 3 component scores ranging from 0 to a maximum of 85, with higher scores denoting worse outcome. If the change from baseline is negative, this represents an improvement in symptoms. |
| Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score for Treatment Cycles 2 to 5 | Treatment cycle Baseline and Week 4 | TWSTRS measures the degree of CD and is comprised of three different components, namely Severity, Disability and Pain subscales. There is an ordinal scale score and range for each component. Severity scores range from 0 (absence of severity) to 35 (maximum severity), Disability scores range from 0 (no disability) to 30 (maximum disability) and Pain scores range from 0 (no pain) to 20 (maximum pain). TWSTRS Total score is the sum of the 3 component scores ranging from 0 to a maximum of 85, with higher scores denoting worse outcome. If the change from baseline is negative, this represents an improvement in symptoms. |
| Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Subscale Score Following First Treatment Cycle | Baseline and Week 4 | TWSTRS measures the degree of CD and comprises three different components, one of which is the Severity subscale. TWSTRS Severity subscale scores range from 0 (absence of severity) to 35 (maximum severity). If the change from baseline is negative, this represents an improvement in symptoms. |
| Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Score for Treatment Cycles 2 to 5 | Treatment cycle Baseline and Week 4 | TWSTRS measures the degree of CD and comprises three different components, one of which is the Disability subscale. TWSTRS Disability subscale scores range from 0 (no disability) to 30 (maximum disability). If the change from baseline is negative, this represents an improvement in symptoms. |
| Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Subscale Score for Treatment Cycles 2 to 5 | Treatment cycle Baseline and Week 4 | TWSTRS measures the degree of CD and comprises three different components, one of which is the Pain subscale. TWSTRS Pain subscale scores range from 0 (no pain) to 20 (maximum pain). If the change from baseline is negative, this represents an improvement in symptoms. |
| Change From Baseline in Subject Visual Analogue Score (VAS) for Pain From Cervical Dystonia for Treatment Cycles 2 to 5 | Treatment cycle Baseline and Week 4 | The assessment was made on a continuous 100-mm horizontal line with a scale range of 0 mm (no pain) to 100 mm (worst possible pain). |
| Change From Baseline in Subject Visual Analogue Score (VAS) for Symptoms of Cervical Dystonia for Treatment Cycles 2 to 5 | Treatment cycle Baseline and Week 4 | The assessment was made on a continuous 100-mm horizontal line with a scale of 0 mm (no symptoms) to 100 mm (worst possible symptoms). |
| Percentage of Treatment Responders for Treatment Cycles 2 to 5 | Treatment cycle Baseline and Week 4 | A treatment responder was defined as a patient with \>30% improvement in TWSTRS Total score compared to baseline. TWSTRS measures the degree of CD and is comprised of three different components, namely Severity, Disability and Pain subscales. There is an ordinal scale score and range for each component. Severity scores range from 0 (absence of severity) to 35 (maximum severity), Disability scores range from 0 (no disability) to 30 (maximum disability) and Pain scores range from 0 (no pain) to 20 (maximum pain). TWSTRS Total score is the sum of the 3 component scores ranging from 0 to a maximum of 85, with higher scores denoting worse outcome. If the change from baseline is negative, this represents an improvement in symptoms. |
| Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Score for Treatment Cycles 2 to 5 | Treatment cycle Baseline and Week 4 | TWSTRS measures the degree of CD and comprises three different components, one of which is the Severity subscale. TWSTRS Severity subscale scores range from 0 (absence of severity) to 35 (maximum severity). If the change from baseline is negative, this represents an improvement in symptoms. |
Countries
Australia, Austria, Belgium, Czechia, France, Germany, Hungary, Poland, Portugal, Russia, Ukraine
Participant flow
Recruitment details
Subjects recruited at 61 centres in Australia (2 subjects), Austria (9 subjects), Belgium (9 subjects), Czech Republic (58 subjects), France (31 subjects), Germany (38 subjects), Hungary (44 subjects), Poland (68 subjects), Portugal (12 subjects), Russia (36 subjects) and Ukraine (62 subjects).
Pre-assignment details
382 subjects screened, 369 randomised due to 13 screen failures.
Participants by arm
| Arm | Count |
|---|---|
| Dysport NG 500U (1mL) administered as intramuscular injection on day 1 of treatment cycle 1 and 2.
250U (0.5mL), 500U (1mL) or 750U (1.5mL) administered as intramuscular injection on day 1 of treatment cycle 3.
250U (0.5mL), 500U (1mL), 750U (1.5mL) or 1000U (2mL) administered as intramuscular injection on day 1 of treatment cycle 4 and 5.
Botulinum type A toxin (Dysport NG): I.M. (in the muscle) injection on day 1 of up to 5 treatment cycles. | 156 |
| Dysport 500U (1mL) injected as intramuscular injection on day 1 of treatment cycle 1.
Botulinum type A toxin (Dysport®): I.M. injection on day 1 of treatment cycle 1. | 159 |
| Placebo 1mL administered as, intramuscular injection on day 1 of treatment cycle 1.
Placebo: I.M. injection on day 1 of treatment cycle 1. | 54 |
| Total | 369 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Treatment Cycle 1 | Adverse Event | 0 | 1 | 0 |
| Treatment Cycle 1 | Lost to Follow-up | 1 | 0 | 0 |
| Treatment Cycle 1 | Protocol Violation | 0 | 0 | 2 |
| Treatment Cycle 1 | Withdrawal by Subject | 3 | 2 | 0 |
| Treatment Cycle 2 | Adverse Event | 1 | 0 | 0 |
| Treatment Cycle 2 | Completed study | 4 | 0 | 0 |
| Treatment Cycle 2 | Not otherwise specified | 2 | 0 | 0 |
| Treatment Cycle 2 | Protocol Violation | 2 | 0 | 0 |
| Treatment Cycle 2 | Withdrawal by Subject | 4 | 0 | 0 |
| Treatment Cycle 3 | Adverse Event | 1 | 0 | 0 |
| Treatment Cycle 3 | Completed study | 24 | 0 | 0 |
| Treatment Cycle 3 | Lost to Follow-up | 1 | 0 | 0 |
| Treatment Cycle 3 | Withdrawal by Subject | 4 | 0 | 0 |
| Treatment Cycle 4 | Adverse Event | 1 | 0 | 0 |
| Treatment Cycle 4 | Completed study | 87 | 0 | 0 |
| Treatment Cycle 4 | Lost to Follow-up | 2 | 0 | 0 |
| Treatment Cycle 4 | Not otherwise specified | 3 | 0 | 0 |
| Treatment Cycle 4 | Withdrawal by Subject | 3 | 0 | 0 |
| Treatment Cycle 5 | Adverse Event | 1 | 0 | 0 |
| Treatment Cycle 5 | Lost to Follow-up | 1 | 0 | 0 |
| Treatment Cycle 5 | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Dysport NG | Dysport | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 51.6 years STANDARD_DEVIATION 12.4 | 49.1 years STANDARD_DEVIATION 12 | 49.7 years STANDARD_DEVIATION 10.8 | 50.3 years STANDARD_DEVIATION 12.1 |
| Baseline Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total score | 44.56 Units on a scale STANDARD_DEVIATION 9.2 | 46.23 Units on a scale STANDARD_DEVIATION 8.82 | 47.02 Units on a scale STANDARD_DEVIATION 9.19 | 45.64 Units on a scale STANDARD_DEVIATION 9.06 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) White | 154 Participants | 154 Participants | 49 Participants | 357 Participants |
| Sex: Female, Male Female | 100 Participants | 101 Participants | 34 Participants | 235 Participants |
| Sex: Female, Male Male | 56 Participants | 58 Participants | 20 Participants | 134 Participants |
| Time since diagnosis of CD, years | 7.13 years STANDARD_DEVIATION 7.95 | 6.88 years STANDARD_DEVIATION 7.49 | 6.25 years STANDARD_DEVIATION 7.31 | 6.84 years STANDARD_DEVIATION 7.63 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 4 | 59 / 363 | 29 / 210 | 7 / 57 | 15 / 156 | 1 / 55 |
| serious Total, serious adverse events | 0 / 4 | 16 / 363 | 3 / 210 | 1 / 57 | 3 / 156 | 0 / 55 |
Outcome results
Primary
Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score Following First Treatment Cycle
TWSTRS measures the degree of CD and is comprised of three different components, namely Severity, Disability and Pain subscales. There is an ordinal scale score and range for each component. Severity scores range from 0 (absence of severity) to 35 (maximum severity), Disability scores range from 0 (no disability) to 30 (maximum disability) and Pain scores range from 0 (no pain) to 20 (maximum pain). TWSTRS Total score is the sum of the 3 component scores ranging from 0 to a maximum of 85, with higher scores denoting worse outcome. If the change from baseline is negative, this represents an improvement in symptoms.
Time frame: Baseline and Week 4
Population: Analysis based on number (n) of subjects in the Intent to Treat (ITT) population (all randomised subjects who received at least one injection of study treatment regardless of the amount of study treatment administered). The ITT population was analysed using subjects as randomised. Missing data were not imputed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score Following First Treatment Cycle | -12.46 Units on a scale |
| Dysport | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score Following First Treatment Cycle | -13.99 Units on a scale |
| Placebo | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score Following First Treatment Cycle | -3.93 Units on a scale |
Comparison: A pre-specified analysis of the LS mean difference between the Dysport NG and Placebo arms was performed. A total of 210 subjects were included in the analysis.p-value: <0.0001ANCOVA
Comparison: A pre-specified analysis of the LS mean difference between the Dysport and Placebo arms was performed. A total of 213 subjects were included in the analysis.p-value: <0.0001ANCOVA
Comparison: A pre-specified analysis of the LS mean difference between the Dysport NG and Dysport arms was performed. A total of 315 subjects were included in the analysis.95% CI: [-0.819, 3.883]
Secondary
Change From Baseline in Subject Visual Analogue Score (VAS) for Pain From Cervical Dystonia Following First Treatment Cycle
The assessment was made on a continuous 100-mm horizontal line with a scale range of 0 mm (no pain) to 100 mm (worst possible pain).
Time frame: Baseline and Week 4
Population: Analysis based on number (n) of subjects in the ITT population (all randomised subjects who received at least one injection of study treatment regardless of the amount of study treatment administered). The ITT population was analysed using subjects as randomised. Missing data were not imputed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Dysport NG | Change From Baseline in Subject Visual Analogue Score (VAS) for Pain From Cervical Dystonia Following First Treatment Cycle | -14.8 Units on a scale |
| Dysport | Change From Baseline in Subject Visual Analogue Score (VAS) for Pain From Cervical Dystonia Following First Treatment Cycle | -19.2 Units on a scale |
| Placebo | Change From Baseline in Subject Visual Analogue Score (VAS) for Pain From Cervical Dystonia Following First Treatment Cycle | -3.4 Units on a scale |
Secondary
Change From Baseline in Subject Visual Analogue Score (VAS) for Pain From Cervical Dystonia for Treatment Cycles 2 to 5
The assessment was made on a continuous 100-mm horizontal line with a scale range of 0 mm (no pain) to 100 mm (worst possible pain).
Time frame: Treatment cycle Baseline and Week 4
Population: Analysis based on number (n) of subjects in the ITT population (all randomised subjects who received at least one injection of study treatment regardless of the amount of study treatment administered) in each cycle. The ITT population was analysed using subjects as randomised. Missing data were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Dysport NG | Change From Baseline in Subject Visual Analogue Score (VAS) for Pain From Cervical Dystonia for Treatment Cycles 2 to 5 | Cycle 2 | -20.1 Units on a scale |
| Dysport NG | Change From Baseline in Subject Visual Analogue Score (VAS) for Pain From Cervical Dystonia for Treatment Cycles 2 to 5 | Cycle 3 | -17.8 Units on a scale |
| Dysport NG | Change From Baseline in Subject Visual Analogue Score (VAS) for Pain From Cervical Dystonia for Treatment Cycles 2 to 5 | Cycle 4 | -18.0 Units on a scale |
| Dysport NG | Change From Baseline in Subject Visual Analogue Score (VAS) for Pain From Cervical Dystonia for Treatment Cycles 2 to 5 | Cycle 5 | -16.1 Units on a scale |
Secondary
Change From Baseline in Subject Visual Analogue Score (VAS) for Symptoms of Cervical Dystonia Following First Treatment Cycle
The assessment was made on a continuous 100-mm horizontal line with a scale range of 0 mm (no symptoms) to 100 mm (worst possible symptoms).
Time frame: Baseline and Week 4
Population: Analysis based on number (n) of subjects in the ITT population (all randomised subjects who received at least one injection of study treatment regardless of the amount of study treatment administered). The ITT population was analysed using subjects as randomised. Missing data were not imputed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Dysport NG | Change From Baseline in Subject Visual Analogue Score (VAS) for Symptoms of Cervical Dystonia Following First Treatment Cycle | -18.7 Units on a scale |
| Dysport | Change From Baseline in Subject Visual Analogue Score (VAS) for Symptoms of Cervical Dystonia Following First Treatment Cycle | -23.6 Units on a scale |
| Placebo | Change From Baseline in Subject Visual Analogue Score (VAS) for Symptoms of Cervical Dystonia Following First Treatment Cycle | -3.3 Units on a scale |
Secondary
Change From Baseline in Subject Visual Analogue Score (VAS) for Symptoms of Cervical Dystonia for Treatment Cycles 2 to 5
The assessment was made on a continuous 100-mm horizontal line with a scale of 0 mm (no symptoms) to 100 mm (worst possible symptoms).
Time frame: Treatment cycle Baseline and Week 4
Population: Analysis based on number (n) of subjects in the ITT population (all randomised subjects who received at least one injection of study treatment regardless of the amount of study treatment administered) in each cycle. The ITT population was analysed using subjects as randomised. Missing data were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Dysport NG | Change From Baseline in Subject Visual Analogue Score (VAS) for Symptoms of Cervical Dystonia for Treatment Cycles 2 to 5 | Cycle 2 | -24.0 Units on a scale |
| Dysport NG | Change From Baseline in Subject Visual Analogue Score (VAS) for Symptoms of Cervical Dystonia for Treatment Cycles 2 to 5 | Cycle 3 | -18.9 Units on a scale |
| Dysport NG | Change From Baseline in Subject Visual Analogue Score (VAS) for Symptoms of Cervical Dystonia for Treatment Cycles 2 to 5 | Cycle 4 | -21.0 Units on a scale |
| Dysport NG | Change From Baseline in Subject Visual Analogue Score (VAS) for Symptoms of Cervical Dystonia for Treatment Cycles 2 to 5 | Cycle 5 | -18.2 Units on a scale |
Secondary
Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Score for Treatment Cycles 2 to 5
TWSTRS measures the degree of CD and comprises three different components, one of which is the Disability subscale. TWSTRS Disability subscale scores range from 0 (no disability) to 30 (maximum disability). If the change from baseline is negative, this represents an improvement in symptoms.
Time frame: Treatment cycle Baseline and Week 4
Population: Analysis based on number (n) of subjects in the ITT population (all randomised subjects who received at least one injection of study treatment regardless of the amount of study treatment administered) in each cycle. The ITT population was analysed using subjects as randomised. Missing data were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Score for Treatment Cycles 2 to 5 | Cycle 2 | -4.7 Units on a scale |
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Score for Treatment Cycles 2 to 5 | Cycle 3 | -4.6 Units on a scale |
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Score for Treatment Cycles 2 to 5 | Cycle 4 | -5.0 Units on a scale |
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Score for Treatment Cycles 2 to 5 | Cycle 5 | -4.9 Units on a scale |
Secondary
Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Subscale Score Following First Treatment Cycle
TWSTRS measures the degree of CD and comprises three different components, one of which is the Disability subscale. TWSTRS Disability subscale scores range from 0 (no disability) to 30 (maximum disability). If the change from baseline is negative, this represents an improvement in symptoms.
Time frame: Baseline and Week 4
Population: Analysis based on number (n) of subjects in the ITT population (all randomised subjects who received at least one injection of study treatment regardless of the amount of study treatment administered). The ITT population was analysed using subjects as randomised. Missing data were not imputed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Subscale Score Following First Treatment Cycle | -3.3 Units on a scale |
| Dysport | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Subscale Score Following First Treatment Cycle | -3.9 Units on a scale |
| Placebo | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Subscale Score Following First Treatment Cycle | -0.8 Units on a scale |
Secondary
Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Subscale Score Following First Treatment Cycle
TWSTRS measures the degree of CD and comprises three different components, one of which is the Pain subscale. TWSTRS Pain subscale scores range from 0 (no pain) to 20 (maximum pain). If the change from baseline is negative, this represents an improvement in symptoms.
Time frame: Baseline and Week 4
Population: Analysis based on number (n) of subjects in the ITT population (all randomised subjects who received at least one injection of study treatment regardless of the amount of study treatment administered). The ITT population was analysed using subjects as randomised. Missing data were not imputed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Subscale Score Following First Treatment Cycle | -3.10 Units on a scale |
| Dysport | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Subscale Score Following First Treatment Cycle | -3.44 Units on a scale |
| Placebo | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Subscale Score Following First Treatment Cycle | -1.21 Units on a scale |
Secondary
Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Subscale Score for Treatment Cycles 2 to 5
TWSTRS measures the degree of CD and comprises three different components, one of which is the Pain subscale. TWSTRS Pain subscale scores range from 0 (no pain) to 20 (maximum pain). If the change from baseline is negative, this represents an improvement in symptoms.
Time frame: Treatment cycle Baseline and Week 4
Population: Analysis based on number (n) of subjects in the ITT population (all randomised subjects who received at least one injection of study treatment regardless of the amount of study treatment administered) in each cycle. The ITT population was analysed using subjects as randomised. Missing data were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Subscale Score for Treatment Cycles 2 to 5 | Cycle 2 | -3.45 Units on a scale |
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Subscale Score for Treatment Cycles 2 to 5 | Cycle 3 | -3.21 Units on a scale |
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Subscale Score for Treatment Cycles 2 to 5 | Cycle 4 | -3.34 Units on a scale |
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Subscale Score for Treatment Cycles 2 to 5 | Cycle 5 | -3.41 Units on a scale |
Secondary
Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Score for Treatment Cycles 2 to 5
TWSTRS measures the degree of CD and comprises three different components, one of which is the Severity subscale. TWSTRS Severity subscale scores range from 0 (absence of severity) to 35 (maximum severity). If the change from baseline is negative, this represents an improvement in symptoms.
Time frame: Treatment cycle Baseline and Week 4
Population: Analysis based on number (n) of subjects in the ITT population (all randomised subjects who received at least one injection of study treatment regardless of the amount of study treatment administered) in each cycle. The ITT population was analysed using subjects as randomised. Missing data were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Score for Treatment Cycles 2 to 5 | Cycle 2 | -7.2 Units on a scale |
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Score for Treatment Cycles 2 to 5 | Cycle 3 | -7.1 Units on a scale |
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Score for Treatment Cycles 2 to 5 | Cycle 4 | -7.3 Units on a scale |
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Score for Treatment Cycles 2 to 5 | Cycle 5 | -7.0 Units on a scale |
Secondary
Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Subscale Score Following First Treatment Cycle
TWSTRS measures the degree of CD and comprises three different components, one of which is the Severity subscale. TWSTRS Severity subscale scores range from 0 (absence of severity) to 35 (maximum severity). If the change from baseline is negative, this represents an improvement in symptoms.
Time frame: Baseline and Week 4
Population: Analysis based on number (n) of subjects in the ITT population (all randomised subjects who received at least one injection of study treatment regardless of the amount of study treatment administered). The ITT population was analysed using subjects as randomised. Missing data were not imputed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Subscale Score Following First Treatment Cycle | -6.2 Units on a scale |
| Dysport | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Subscale Score Following First Treatment Cycle | -6.6 Units on a scale |
| Placebo | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Subscale Score Following First Treatment Cycle | -1.9 Units on a scale |
Secondary
Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score for Treatment Cycles 2 to 5
TWSTRS measures the degree of CD and is comprised of three different components, namely Severity, Disability and Pain subscales. There is an ordinal scale score and range for each component. Severity scores range from 0 (absence of severity) to 35 (maximum severity), Disability scores range from 0 (no disability) to 30 (maximum disability) and Pain scores range from 0 (no pain) to 20 (maximum pain). TWSTRS Total score is the sum of the 3 component scores ranging from 0 to a maximum of 85, with higher scores denoting worse outcome. If the change from baseline is negative, this represents an improvement in symptoms.
Time frame: Treatment cycle Baseline and Week 4
Population: Analysis based on number (n) of subjects in the ITT population (all randomised subjects who received at least one injection of study treatment regardless of the amount of study treatment administered) in each cycle. The ITT population was analysed using subjects as randomised. Missing data were not imputed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score for Treatment Cycles 2 to 5 | Cycle 2 | -15.35 Units on a scale |
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score for Treatment Cycles 2 to 5 | Cycle 3 | -14.85 Units on a scale |
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score for Treatment Cycles 2 to 5 | Cycle 4 | -15.58 Units on a scale |
| Dysport NG | Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score for Treatment Cycles 2 to 5 | Cycle 5 | -15.28 Units on a scale |
Secondary
Percentage of Treatment Responders Following First Treatment Cycle
A treatment responder was defined as a patient with \>30% improvement in TWSTRS Total score compared to baseline. TWSTRS measures the degree of CD and is comprised of three different components, namely Severity, Disability and Pain subscales. There is an ordinal scale score and range for each component. Severity scores range from 0 (absence of severity) to 35 (maximum severity), Disability scores range from 0 (no disability) to 30 (maximum disability) and Pain scores range from 0 (no pain) to 20 (maximum pain). TWSTRS Total score is the sum of the 3 component scores ranging from 0 to a maximum of 85, with higher scores denoting worse outcome. If the change from baseline is negative, this represents an improvement in symptoms.
Time frame: Baseline and Week 4
Population: Analysis based on number (n) of subjects in the ITT population (all randomised subjects who received at least one injection of study treatment regardless of the amount of study treatment administered). The ITT population was analysed using subjects as randomised. Missing data were not imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dysport NG | Percentage of Treatment Responders Following First Treatment Cycle | 45.8 Percentage of participants |
| Dysport | Percentage of Treatment Responders Following First Treatment Cycle | 55.8 Percentage of participants |
| Placebo | Percentage of Treatment Responders Following First Treatment Cycle | 20.8 Percentage of participants |
Secondary
Percentage of Treatment Responders for Treatment Cycles 2 to 5
A treatment responder was defined as a patient with \>30% improvement in TWSTRS Total score compared to baseline. TWSTRS measures the degree of CD and is comprised of three different components, namely Severity, Disability and Pain subscales. There is an ordinal scale score and range for each component. Severity scores range from 0 (absence of severity) to 35 (maximum severity), Disability scores range from 0 (no disability) to 30 (maximum disability) and Pain scores range from 0 (no pain) to 20 (maximum pain). TWSTRS Total score is the sum of the 3 component scores ranging from 0 to a maximum of 85, with higher scores denoting worse outcome. If the change from baseline is negative, this represents an improvement in symptoms.
Time frame: Treatment cycle Baseline and Week 4
Population: Analysis based on number (n) of subjects in the ITT population (all randomised subjects who received at least one injection of study treatment regardless of the amount of study treatment administered) in each cycle. The ITT population was analysed using subjects as randomised. Missing data were not imputed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dysport NG | Percentage of Treatment Responders for Treatment Cycles 2 to 5 | Cycle 2 | 58.5 Percentage of participants |
| Dysport NG | Percentage of Treatment Responders for Treatment Cycles 2 to 5 | Cycle 3 | 56.8 Percentage of participants |
| Dysport NG | Percentage of Treatment Responders for Treatment Cycles 2 to 5 | Cycle 4 | 63.5 Percentage of participants |
| Dysport NG | Percentage of Treatment Responders for Treatment Cycles 2 to 5 | Cycle 5 | 57.5 Percentage of participants |