Clinical trial NCT01261611: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cervical Dystonia
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2010-12-16
Enrollment: 382
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score Following First Treatment Cycle
timeFrame: Baseline and Week 4
Secondary outcomes:
measure: Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Subscale Score Following First Treatment Cycle
timeFrame: Baseline and Week 4
measure: Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Subscale Score Following First Treatment Cycle
timeFrame: Baseline and Week 4
measure: Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Subscale Score Following First Treatment Cycle
timeFrame: Baseline and Week 4
measure: Change From Baseline in Subject Visual Analogue Score (VAS) for Pain From Cervical Dystonia Following First Treatment Cycle
timeFrame: Baseline and Week 4
measure: Change From Baseline in Subject Visual Analogue Score (VAS) for Symptoms of Cervical Dystonia Following First Treatment Cycle
timeFrame: Baseline and Week 4
measure: Percentage of Treatment Responders Following First Treatment Cycle
timeFrame: Baseline and Week 4
measure: Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score for Treatment Cycles 2 to 5
timeFrame: Treatment cycle Baseline and Week 4
measure: Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Score for Treatment Cycles 2 to 5
timeFrame: Treatment cycle Baseline and Week 4
measure: Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Score for Treatment Cycles 2 to 5
timeFrame: Treatment cycle Baseline and Week 4
measure: Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Subscale Score for Treatment Cycles 2 to 5
timeFrame: Treatment cycle Baseline and Week 4
measure: Change From Baseline in Subject Visual Analogue Score (VAS) for Pain From Cervical Dystonia for Treatment Cycles 2 to 5
timeFrame: Treatment cycle Baseline and Week 4
measure: Change From Baseline in Subject Visual Analogue Score (VAS) for Symptoms of Cervical Dystonia for Treatment Cycles 2 to 5
timeFrame: Treatment cycle Baseline and Week 4
measure: Percentage of Treatment Responders for Treatment Cycles 2 to 5
timeFrame: Treatment cycle Baseline and Week 4
Other outcomes:
Locations:
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Heidelberg
country: Australia
facility: Austin Hospital
city: Prahran
country: Australia
facility: Department of Neurosciences Alfred Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Innsbruck
country: Austria
facility: Univ.-Klinik für Neurologie
city: Wien
country: Austria
facility: Univ.-Klinik für Neurologie
city: Brugge
country: Belgium
facility: AZ St. Jan
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: AZ Sint Lucas
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
city: Roeselare
country: Belgium
facility: HH Ziekenhuis
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Pardubice
country: Czechia
facility: Pardubicka krajska nemocnice
city: Plzen
country: Czechia
facility: RESEARCH SITE s.r.o.
city: Praha
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Amiens
country: France
facility: CHU Amiens
city: Bron
country: France
facility: Hopital Neurologique
city: Nîmes
country: France
facility: CHU Caremeau
city: Pessac
country: France
facility: CHU Bordeaux
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Toulouse
country: France
facility: Hopital Purpan
city: Berlin
country: Germany
facility: Neurologische Klinik u. Poliklinik
city: Bonn
country: Germany
facility: Neurologische Klinik u. Poliklinik
city: Düsseldorf
country: Germany
facility: Neurologische Klinik
city: Halle
country: Germany
facility: Neurologische Klinik
city: Hannover
country: Germany
facility: Neurologische Klinik
city: Leipzig
country: Germany
facility: Neurologische Klinik
city: München
country: Germany
facility: Neurologische Klinik
city: Tübingen
country: Germany
facility: Neurologische Klinik
city: Wiesbaden
country: Germany
facility: Neurologische Klinik
city: Würzburg
country: Germany
facility: Neurologische Klinik
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Nyíregyháza
country: Hungary
facility: Jósa András Oktató Kórház Nonprofit Kft.
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
city: Gdansk
country: Poland
facility: Pomorskie Centrum Traumatologii im. M. Kopernika w Gdansku
city: Katowice
country: Poland
facility: Specjalistyczna Praktyka Lekarska
city: Krakow
country: Poland
facility: Malopolskie Centrum Medyczne
city: Lodz
country: Poland
facility: Gabinet Lekarski
city: Poznan
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny
city: Lisboa
country: Portugal
facility: Hospital Santa Maria
city: Porto
country: Portugal
facility: Hospital Geral de Santo Antonio
city: Kazan
country: Russian Federation
facility: Research Medical Complex "Vashe Zdorovie"
city: Moscow
country: Russian Federation
facility: Research Center of Neurology of RAMS
city: Nizhniy Novgorod
country: Russian Federation
facility: Nizhniy Novgorod Research Institute for Traumatology and Orthopaedics
city: Samara
country: Russian Federation
facility: Samara Regional Clinical Hospital
city: Smolensk
country: Russian Federation
facility: Smolensk State Medical Academy Smolensk Regional Clinical Hospital
city: St. Petersburg
country: Russian Federation
facility: Russian Medical Military Academy n.a. S.M.Kirov
city: Chernivtsi
country: Ukraine
facility: Bukovinian Medical State University
city: Dnipropetrovsk
country: Ukraine
facility: Ukrainian State Institute of Medical and Social Problems of Disability
city: Donetsk
country: Ukraine
facility: Donetsk Railroad Clinical Hospital
city: Kharkiv
country: Ukraine
facility: Institute of Neurology, Psychiatry and Narcology AMS of Ukraine
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Hospital
city: Odessa
country: Ukraine
facility: Municipal Institution "Odesa Regional Clinical Hospital"
city: Uzhgorod
country: Ukraine
facility: Uzhgorod National University
city: Vinnytsya
country: Ukraine
facility: Vinnytsya National Medical University
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.