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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-019907-43 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dysport NG | Experimental | 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. |
|
| Dysport | Active Comparator | 500U (1mL) injected as intramuscular injection on day 1 of treatment cycle 1. |
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| Placebo | Placebo Comparator | 1mL administered as, intramuscular injection on day 1 of treatment cycle 1. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Botulinum toxin type A | Biological | I.M. (in the muscle) injection on day 1 of up to 5 treatment cycles. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and Week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ipsen Medical Director | Ipsen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Monash Medical Centre | Clayton | Australia | ||||
| Austin Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27653448 | Derived | Poewe W, Burbaud P, Castelnovo G, Jost WH, Ceballos-Baumann AO, Banach M, Potulska-Chromik A, Ferreira JJ, Bihari K, Ehler E, Bares M, Dzyak LA, Belova AN, Pham E, Liu WJ, Picaut P. Efficacy and safety of abobotulinumtoxinA liquid formulation in cervical dystonia: A randomized-controlled trial. Mov Disord. 2016 Nov;31(11):1649-1657. doi: 10.1002/mds.26760. Epub 2016 Sep 21. |
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Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants.
Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.
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Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
382 subjects screened, 369 randomised due to 13 screen failures.
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | Dysport NG | Up to 5 treatment cycles of Dysport NG |
| FG001 | Dysport | 1 treatment cycle of Dysport |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Cycle 1 |
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| Botulinum toxin type A | Biological | I.M. injection on day 1 of treatment cycle 1. |
|
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| Placebo | Drug | I.M. injection on day 1 of treatment cycle 1. |
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| Baseline and Week 4 |
| 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. | Baseline and Week 4 |
| 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. | Baseline and Week 4 |
| 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). | Baseline and Week 4 |
| 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). | Baseline and Week 4 |
| 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. | Baseline and Week 4 |
| 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. | Treatment cycle Baseline and Week 4 |
| 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. | Treatment cycle Baseline and Week 4 |
| 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. | Treatment cycle Baseline and Week 4 |
| 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. | Treatment cycle Baseline and Week 4 |
| 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). | Treatment cycle Baseline and Week 4 |
| 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). | Treatment cycle Baseline and Week 4 |
| 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. | Treatment cycle Baseline and Week 4 |
| Heidelberg |
| Australia |
| Department of Neurosciences Alfred Hospital | Prahran | Australia |
| Westmead Hospital | Westmead | Australia |
| Univ.-Klinik für Neurologie | Innsbruck | Austria |
| Univ.-Klinik für Neurologie | Vienna | Austria |
| AZ St. Jan | Bruges | Belgium |
| Universitair Ziekenhuis Antwerpen | Edegem | Belgium |
| AZ Sint Lucas | Ghent | Belgium |
| Centre Hospitalier Universitaire de Liège | Liège | Belgium |
| HH Ziekenhuis | Roeselare | Belgium |
| Fakultni nemocnice Brno | Brno | Czechia |
| Pardubicka krajska nemocnice | Pardubice | Czechia |
| RESEARCH SITE s.r.o. | Pilsen | Czechia |
| Vseobecna fakultni nemocnice v Praze | Prague | Czechia |
| CHU Amiens | Amiens | France |
| Hopital Neurologique | Bron | France |
| CHU Caremeau | Nîmes | France |
| CHU Bordeaux | Pessac | France |
| CHU Strasbourg | Strasbourg | France |
| Hopital Purpan | Toulouse | France |
| Neurologische Klinik u. Poliklinik | Berlin | Germany |
| Neurologische Klinik u. Poliklinik | Bonn | Germany |
| Neurologische Klinik | Düsseldorf | Germany |
| Neurologische Klinik | Halle | Germany |
| Neurologische Klinik | Hanover | Germany |
| Neurologische Klinik | Leipzig | Germany |
| Neurologische Klinik | München | Germany |
| Neurologische Klinik | Tübingen | Germany |
| Neurologische Klinik | Wiesbaden | Germany |
| Neurologische Klinik | Würzburg | Germany |
| Semmelweis Egyetem | Budapest | Hungary |
| Jósa András Oktató Kórház Nonprofit Kft. | NyÃregyháza | Hungary |
| Pécsi Tudományegyetem | Pécs | Hungary |
| Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ | Szeged | Hungary |
| Pomorskie Centrum Traumatologii im. M. Kopernika w Gdansku | Gdansk | Poland |
| Specjalistyczna Praktyka Lekarska | Katowice | Poland |
| Malopolskie Centrum Medyczne | Krakow | Poland |
| Gabinet Lekarski | Lodz | Poland |
| Niepubliczny Zaklad Opieki Zdrowotnej | Poznan | Poland |
| Samodzielny Publiczny Centralny Szpital Kliniczny | Warsaw | Poland |
| Hospital Santa Maria | Lisbon | Portugal |
| Hospital Geral de Santo Antonio | Porto | Portugal |
| Research Medical Complex "Vashe Zdorovie" | Kazan' | Russia |
| Research Center of Neurology of RAMS | Moscow | Russia |
| Nizhniy Novgorod Research Institute for Traumatology and Orthopaedics | Nizhny Novgorod | Russia |
| Russian Medical Military Academy n.a. S.M.Kirov | Saint Petersburg | Russia |
| Samara Regional Clinical Hospital | Samara | Russia |
| Smolensk State Medical Academy Smolensk Regional Clinical Hospital | Smolensk | Russia |
| Bukovinian Medical State University | Chernivtsi | Ukraine |
| Ukrainian State Institute of Medical and Social Problems of Disability | Dnipropetrovsk | Ukraine |
| Donetsk Railroad Clinical Hospital | Donetsk | Ukraine |
| Institute of Neurology, Psychiatry and Narcology AMS of Ukraine | Kharkiv | Ukraine |
| Lviv Regional Clinical Hospital | Lviv | Ukraine |
| Municipal Institution "Odesa Regional Clinical Hospital" | Odesa | Ukraine |
| Uzhgorod National University | Uzhhorod | Ukraine |
| Vinnytsya National Medical University | Vinnytsia | Ukraine |
| FG002 |
| Placebo |
1 treatment cycle of placebo |
| COMPLETED |
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| NOT COMPLETED |
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| Treatment Cycle 2 |
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| Treatment Cycle 3 |
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| Treatment Cycle 4 |
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| Treatment Cycle 5 |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Placebo | 1mL administered as, intramuscular injection on day 1 of treatment cycle 1. Placebo: I.M. injection on day 1 of treatment cycle 1. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Time since diagnosis of CD, years | Mean | Standard Deviation | years |
| |||||||||||||||
| Baseline Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total score | 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. | Mean | Standard Deviation | Units on a scale |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Units on a scale | Baseline and Week 4 |
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| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Units on a scale | Baseline and Week 4 |
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| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Units on a scale | Baseline and Week 4 |
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| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Units on a scale | Baseline and Week 4 |
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| 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). | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Units on a scale | Baseline and Week 4 |
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| 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). | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Units on a scale | Baseline and Week 4 |
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| 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. | 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. | Posted | Number | Percentage of participants | Baseline and Week 4 |
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| 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. | 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. | Posted | Mean | 95% Confidence Interval | Units on a scale | Treatment cycle Baseline and Week 4 |
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| 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. | 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. | Posted | Mean | 95% Confidence Interval | Units on a scale | Treatment cycle Baseline and Week 4 |
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| 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. | 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. | Posted | Mean | 95% Confidence Interval | Units on a scale | Treatment cycle Baseline and Week 4 |
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| 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. | 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. | Posted | Mean | 95% Confidence Interval | Units on a scale | Treatment cycle Baseline and Week 4 |
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| 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). | 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. | Posted | Mean | 95% Confidence Interval | Units on a scale | Treatment cycle Baseline and Week 4 |
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| 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). | 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. | Posted | Mean | 95% Confidence Interval | Units on a scale | Treatment cycle Baseline and Week 4 |
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| 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. | 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. | Posted | Number | Percentage of participants | Treatment cycle Baseline and Week 4 |
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2 years
Analysis based on number of subjects in the safety population (all randomised subjects who received at least one injection of study treatment). One subject was randomised to Dysport 500 U but actually received placebo; therefore, this subject was counted in the placebo group for the safety population analysis (n=55 not n=54). Data are broken down by dose across all treatment cycles and the denominator (total number of patients at risk) for each group could not be reported in participant flow.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dysport NG, 250U | Subjects in the safety population were analysed as treated. | 0 | 4 | 1 | 4 | ||
| EG001 | Dysport NG, 500U | Subjects in the safety population were analysed as treated. | 16 | 363 | 59 | 363 | ||
| EG002 | Dysport NG, 750U | Subjects in the safety population were analysed as treated. | 3 | 210 | 29 | 210 | ||
| EG003 | Dysport NG, 1000U | Subjects in the safety population were analysed as treated. | 1 | 57 | 7 | 57 | ||
| EG004 | Dysport, 500U | The safety population was analysed using subjects as treated. One subject was randomised to Dysport 500 U but actually received placebo; therefore, this subject was counted in the placebo group for the safety population, and the Dysport group for the ITT population. | 3 | 156 | 15 | 156 | ||
| EG005 | Placebo | The safety population was analysed using subjects as treated. One subject was randomised to Dysport 500 U but actually received placebo; therefore, this subject was counted in the placebo group for the safety population, and the Dysport group for the ITT population. | 0 | 55 | 1 | 55 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute coronary syndrome | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
| |
| Alcohol withdrawal syndrome | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Clavicle fracture | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
| |
| Completed suicide | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Fibula fracture | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
| |
| Gastric ulcer haemorrhage | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Lung adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
| |
| Malignant pleural effusion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
| |
| Meniscus injury | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
| |
| Paget-Schroetter syndrome | Vascular disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Pericardial effusion malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
| |
| Pneumonia streptococcal | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Proctitis infectious | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Thyroid cyst | Endocrine disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
| |
| Uterine polyp | Reproductive system and breast disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Vaginal abscess | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Gastritis haemorrhagic | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Gastrooesphageal reflux disease | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Rectal perforation | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Aortic dissection | Vascular disorders | MedDRA 16.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dysphagia | Gastrointestinal disorders | MedDRA version 16.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA version 16.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA version 16.0 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director, Neurology | Ipsen Innovation | clinical.trials@ipsen.com | clinical.trials@ipsen.com |
| ID | Term |
|---|---|
| D014103 | Torticollis |
| ID | Term |
|---|---|
| D004421 | Dystonia |
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D019274 | Botulinum Toxins, Type A |
| C542869 | abobotulinumtoxinA |
| ID | Term |
|---|---|
| D001905 | Botulinum Toxins |
| D008666 | Metalloendopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D045726 | Metalloproteases |
| D001426 | Bacterial Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |
Not provided
Not provided
| Adverse Event |
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| Protocol Violation |
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| Not otherwise specified |
|
| Adverse Event |
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| Lost to Follow-up |
|
| Adverse Event |
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| Lost to Follow-up |
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| Not otherwise specified |
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| Lost to Follow-up |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
|
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. |
| ANCOVA |
An ANCOVA on the change from baseline, baseline TWSTRS Total score, baseline BTX status and pooled centre as explanatory variables was performed. |
| <0.0001 |
| Superiority or Other (legacy) |
| 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. | LS mean difference | 1.532 | 2-Sided | 95 | -0.819 | 3.883 | Non-Inferiority or Equivalence (legacy) | An ANCOVA on the change from baseline with treatment, baseline TWSTRS Total score, BTX status at baseline and pooled centre as explanatory variables had been performed. The non-inferiority margin was 3 points. |
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