IncobotulinumtoxinA (Xeomin) to Treat Focal Hand Dystonia

Study Overview
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Brief Summary
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This study is a multicenter, double-blind, randomized placebo controlled, parallel group, superiority trial in order to test the superiority of intramuscular injections of IncobotulinumtoxinA against placebo using a 1:1 allocation ratio.

Detailed Description
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After a baseline evaluation, each patient will receive a first injection of IncobotulinumtoxinA or placebo (50:50 randomization) in a double blinding setting. Assessment of the Focal hand dystonia (FHD) will be done at each site by an investigator blinded to the treatment. A first evaluation of the efficacy will be performed after 6 weeks. After 6 weeks, patients unsatisfied with treatment and wishing to continue the treatment will receive an injection of IncobotulinumtoxinA regardless of the treatment arm they were initially assigned to at baseline. These patients will subsequently be excluded from the study. A second assessment will be performed after 12 weeks (only for patients not receiving a second injection of IncobotulinumtoxinA at week 6).

Official Title
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IncobotulinumtoxinA (Xeomin) to Treat Focal Hand Dystonia: a Double-blind Placebo-controlled Randomized Multicenter Study: The SwissHandSpasm Study

Conditions
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Focal Hand Dystonia

Intervention / Treatment
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* Drug: Xeomin
* Drug: Placebo - Concentrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent as documented by signature Age ≥ 18 years Focal hand dystonia (FHD). Diagnosis must be made by a neurologist specialized in movement disorder (at least 2 years specific training, all partners listed have at least 2 years training) Both idiopathic and secondary FHD are allowed Both drug naive subjects and subjects previously treated with other BoNT-A will be included Patients must be willing and able to comply with the study procedures Female patients of childbearing potential must agree to use an effective method of contraception during the treatment period Exclusion Criteria: Presence of spasticity, or other central sensorimotor lesion of motor system other than dystonia in the affected limb Peripheral nerve lesion (diagnosis either clinical or electrophysiological) in the affected limb, for example with a muscle weakness at baseline Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to BoNT-A toxins including IncobotulinumtoxinA Doses and schedules of any ongoing treatment with potential confounding drugs such as muscle relaxants (for example Tolperison, Tizinadid, Baclofen, Mestinon, Dantrolen), benzodiazepine, neuroleptics or antidepressants have to be kept unchanged throughout the study and no changes should be made between the first trial injection and the end of study visit at week 12. Previous treatment with other BoNT-A less than 3 months before the inclusion in this study Women who are pregnant or breast feeding, Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant Participation in another study with investigational drug within the 30 days preceding and during the present study Previous enrolment into the current study Enrolment of the investigator, his/her family members, employees and other dependent persons Severe depression (>29 as measured with the Beck Depression Inventory, see Appendix 8) or other relevant psychiatric disorder INR > 2 on the day of injection if the patient is anticoagulated. If INR > 2, the study injection will be delayed until the return to a safer INR.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Xeomin®<br>Intramuscular IncobotulinumtoxinA (Xeomin®) injection under guidance (EMG and/or sonographic monitoring), 2.5 to 40 U in each muscle (max. 5 forearm- and/or hand muscles). | Drug: Xeomin<br>* One injection of 2.5 to 40 U in each muscle. Injection repeated after 6 weeks if considered necessary<br>|
| Placebo Comparator: Placebo concentrate<br>Intramuscular Placebo injection under guidance (EMG and/or sonographic monitoring), in each muscle (max. 5 forearm- and/or hand muscles). | Drug: Placebo - Concentrate<br>* One injection in each muscle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the efficacy of IncobotulinumtoxinA on focal hand dystonia (FHD) | To evaluate patient's subjective impairment due to FHD on VAS for handwriting. The VAS for handwriting is a self-assessment scale drawn by the patients on a 10-cm line, on which 0 indicates the worst possible situation and 10 the best possible situation. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the efficacy of IncobotulinumtoxinA on FHD | To evaluate patient's subjective impairment due to FHD on VAS for handwriting. The VAS for handwriting is a self-assessment scale drawn by the patients on a 10-cm line, on which 0 indicates the worst possible situation and 10 the best possible situation. | 12 weeks | 
| Evaluation of the effect of IncobotulinumtoxinA on FHD symptoms severity | To measure change in symptoms severity by using the Symptom Severity Scale (SSS). Total SSS score ranges from 10 (best possible) to 43 (worst possible). | 6 and 12 weeks | 
| Evaluation of the effect of IncobotulinumtoxinA on functional status | To measure change in functional status by using the Functional Status Scale (FSS). Total FSS score ranges from 0 (best possible) to 40 (worst possible). | 6 and 12 weeks | 
| Evaluation of the effect of IncobotulinumtoxinA on writer's cramp improvement | To measure the change in writer's cramp measured by the Writer's Cramp Rating Scale (WCRS) - only part A. Total WCRS score ranges from 0 (no improvement) to 28 (marked improvement). | 6 and 12 weeks | 
| Evaluation of the effect of IncobotulinumtoxinA on disease improvement | To measure the change in the physician's clinical evaluation of the disease by using the CGI-improvement scale. The CGI-improvement scale ranges from 0 to 4 (none, minimal, mild, moderate, excellent). | 6 and 12 weeks | 
| Evaluation of the effect of IncobotulinumtoxinA on writing pressure | To measure the change in writing pressure by using a pressure sensitive-tablet. Writing Movement pressure will be measured in Pascal. | 6 and 12 weeks | 
| Evaluation of the effect of IncobotulinumtoxinA on writing speed | To measure the change in writing speed by using a pressure sensitive-tablet. Writing movement speed will be measured in seconds. | 6 and 12 weeks | 
| Evaluation of the effect of IncobotulinumtoxinA on muscle strength | To measure the change in muscle strength by using the Medical Research Council Scale for Muscle strength. The patient's effort is graded on a scale of 0 (normal muscle) to 5 (no movement). | 6 and 12 weeks | 
| Evaluation of the responders to IncobotulinumtoxinA treatment | Number of patients showing an improvement of FHD by ≥ 1 points over baseline | 6 and 12 weeks | 
| Evaluation of the overall satisfaction of the patients following IncobotulinumtoxinA treatment | Patients will answer the following two questions: a) Considering all advantages and disadvantages of this treatment, is the improvement such that you wish to continue this treatment or not? Yes/No b) Do you think that you would need an injection of IncobotulinumtoxinA today? Yes/No | 6 weeks | 
| Need of re-injection | The physician will judge about whether an injection with IncobotulinumtoxinA is recommended or not (Yes/No) | 6 weeks | 
| Safety outcomes: adverse events | Incidence and severity of adverse reactions (mild, moderate, severe). | 6 and 12 weeks | 
| Safety outcomes: pain | Pain assessed by VAS scale. The VAS for pain is a self-assessment scale drawn by the patients on a 10-cm line, on which 0 indicates no pain and 10 an extreme amount of pain. | 6 and 12 weeks | 
| Safety outcomes: weakness | Weakness assessed by using the CGI-side effect scale and CGI-weakness scale. CGI-side effect scale ranges from 0 to 3 (no, mild, marked, severe side effects). CGI-weakness assessment scale ranges from 0 to 4 (none, <25%, 26-50%, 51-75%, 76-100% reduction in normal strength). | 6 and 12 weeks | 
| Evaluation of the effect of IncobotulinumtoxinA on depressive symptoms | To measure the change in depressive symptoms by using the Beck Depression Inventory (BDI). Total BDI score ranges from 0 to 63 with scores > 29 indicating severe depression and > 40 extreme depression. | 6 and 12 weeks |