Study Comparing Short Term Efficacy of Dysport and Dysport NG to Placebo, and to Assess Efficacy and Safety of Dysport NG of Subjects With Cervical Dystonia

Cervical Dystonia Clinical Trial

Official title:

A Phase III, Randomised, Double-blind and Open Label Phase, Active and Placebo Controlled Study Comparing the Short-term Efficacy of Two Formulations of Clostridium Botulinum Type A Toxin (Dysport and Dysport NG) to Placebo, and Assessing the Short and Long Term Efficacy and Safety of Dysport NG Following Repeated Treatments of Subjects With Cervical Dystonia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01261611
• Other study ID #: Y-52-52120-134
• Secondary ID: 2010-019907-43
• Status: Completed
• Phase: Phase 3
• Start date: April 2011
• Est. completion date: June 2013

Study information

• Verified date: September 2022
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 382
• Est. completion date: June 2013
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cervical Dystonia
• Dystonia
• Dystonic Disorders
• Torticollis

Intervention

Biological:
• Botulinum toxin type A
I.M. (in the muscle) injection on day 1 of up to 5 treatment cycles.
• Botulinum toxin type A
I.M. injection on day 1 of treatment cycle 1.

Drug:
• Placebo
I.M. injection on day 1 of treatment cycle 1.

Locations

Country	Name	City	State
Australia	Monash Medical Centre	Clayton
Australia	Austin Hospital	Heidelberg
Australia	Department of Neurosciences Alfred Hospital	Prahran
Australia	Westmead Hospital	Westmead
Austria	Univ.-Klinik für Neurologie	Innsbruck
Austria	Univ.-Klinik für Neurologie	Wien
Belgium	AZ St. Jan	Brugge
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	AZ Sint Lucas	Gent
Belgium	Centre Hospitalier Universitaire de Liège	Liège
Belgium	HH Ziekenhuis	Roeselare
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Pardubicka krajska nemocnice	Pardubice
Czechia	RESEARCH SITE s.r.o.	Plzen
Czechia	Vseobecna fakultni nemocnice v Praze	Praha
France	CHU Amiens	Amiens
France	Hopital Neurologique	Bron
France	CHU Caremeau	Nîmes
France	CHU Bordeaux	Pessac
France	CHU Strasbourg	Strasbourg
France	Hopital Purpan	Toulouse
Germany	Neurologische Klinik u. Poliklinik	Berlin
Germany	Neurologische Klinik u. Poliklinik	Bonn
Germany	Neurologische Klinik	Düsseldorf
Germany	Neurologische Klinik	Halle
Germany	Neurologische Klinik	Hannover
Germany	Neurologische Klinik	Leipzig
Germany	Neurologische Klinik	München
Germany	Neurologische Klinik	Tübingen
Germany	Neurologische Klinik	Wiesbaden
Germany	Neurologische Klinik	Würzburg
Hungary	Semmelweis Egyetem	Budapest
Hungary	Jósa András Oktató Kórház Nonprofit Kft.	Nyíregyháza
Hungary	Pécsi Tudományegyetem	Pécs
Hungary	Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ	Szeged
Poland	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	Warszawa
Portugal	Hospital Santa Maria	Lisboa
Portugal	Hospital Geral de Santo Antonio	Porto
Russian Federation	Research Medical Complex "Vashe Zdorovie"	Kazan
Russian Federation	Research Center of Neurology of RAMS	Moscow
Russian Federation	Nizhniy Novgorod Research Institute for Traumatology and Orthopaedics	Nizhniy Novgorod
Russian Federation	Samara Regional Clinical Hospital	Samara
Russian Federation	Smolensk State Medical Academy Smolensk Regional Clinical Hospital	Smolensk
Russian Federation	Russian Medical Military Academy n.a. S.M.Kirov	St. Petersburg
Ukraine	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"	Odessa
Ukraine	Uzhgorod National University	Uzhgorod
Ukraine	Vinnytsya National Medical University	Vinnytsya

Sponsors (1)

Lead Sponsor	Collaborator
Ipsen

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Czechia,  France,  Germany,  Hungary,  Poland,  Portugal,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline and Week 4
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.	Baseline and Week 4
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.	Baseline and Week 4
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.	Baseline and Week 4
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).	Baseline and Week 4
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).	Baseline and Week 4
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.	Baseline and Week 4
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.	Treatment cycle Baseline and Week 4
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.	Treatment cycle Baseline and Week 4
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.	Treatment cycle Baseline and Week 4
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.	Treatment cycle Baseline and Week 4
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).	Treatment cycle Baseline and Week 4
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).	Treatment cycle Baseline and Week 4
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.	Treatment cycle Baseline and Week 4