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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01261611
Recruitment Status : Completed
First Posted : December 16, 2010
Results First Posted : September 24, 2019
Last Update Posted : September 24, 2019
Sponsor:
Information provided by (Responsible Party):
Ipsen

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.

Condition or disease Intervention/treatment Phase
Cervical Dystonia Biological: Botulinum toxin type A Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 382 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : April 2011
Actual Primary Completion Date : May 2012
Actual Study Completion Date : June 2013


Arm Intervention/treatment
Experimental: 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.

Biological: Botulinum toxin type A
I.M. (in the muscle) injection on day 1 of up to 5 treatment cycles.
Other Name: AbobotulinumtoxinA (DysportRU®)

Active Comparator: Dysport
500U (1mL) injected as intramuscular injection on day 1 of treatment cycle 1.
Biological: Botulinum toxin type A
I.M. injection on day 1 of treatment cycle 1.
Other Name: AbobotulinumtoxinA (Dysport®)

Placebo Comparator: Placebo
1mL administered as, intramuscular injection on day 1 of treatment cycle 1.
Drug: Placebo
I.M. injection on day 1 of treatment cycle 1.




Primary Outcome Measures :
  1. Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score Following First Treatment Cycle [ Time Frame: 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 Outcome Measures :
  1. Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Subscale Score Following First Treatment Cycle [ Time Frame: 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.

  2. Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Subscale Score Following First Treatment Cycle [ Time Frame: 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.

  3. Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Subscale Score Following First Treatment Cycle [ Time Frame: 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.

  4. Change From Baseline in Subject Visual Analogue Score (VAS) for Pain From Cervical Dystonia Following First Treatment Cycle [ Time Frame: 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).

  5. Change From Baseline in Subject Visual Analogue Score (VAS) for Symptoms of Cervical Dystonia Following First Treatment Cycle [ Time Frame: 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).

  6. Percentage of Treatment Responders Following First Treatment Cycle [ Time Frame: 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.


  7. Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score for Treatment Cycles 2 to 5 [ Time Frame: 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.

  8. Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Score for Treatment Cycles 2 to 5 [ Time Frame: 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.

  9. Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Disability Score for Treatment Cycles 2 to 5 [ Time Frame: 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.

  10. Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Pain Subscale Score for Treatment Cycles 2 to 5 [ Time Frame: 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.

  11. Change From Baseline in Subject Visual Analogue Score (VAS) for Pain From Cervical Dystonia for Treatment Cycles 2 to 5 [ Time Frame: 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).

  12. Change From Baseline in Subject Visual Analogue Score (VAS) for Symptoms of Cervical Dystonia for Treatment Cycles 2 to 5 [ Time Frame: 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).

  13. Percentage of Treatment Responders for Treatment Cycles 2 to 5 [ Time Frame: 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.




Information from the National Library of Medicine

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Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01261611


Locations
Show Show 57 study locations
Sponsors and Collaborators
Ipsen
Investigators
Layout table for investigator information
Study Director: Ipsen Medical Director Ipsen
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT01261611    
Other Study ID Numbers: Y-52-52120-134
2010-019907-43 ( EudraCT Number )
First Posted: December 16, 2010    Key Record Dates
Results First Posted: September 24, 2019
Last Update Posted: September 24, 2019
Last Verified: September 2019
Additional relevant MeSH terms:
Layout table for MeSH terms
Dystonia
Dystonic Disorders
Torticollis
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Movement Disorders
Central Nervous System Diseases
Botulinum Toxins
Botulinum Toxins, Type A
abobotulinumtoxinA
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents