IncobotulinumtoxinA (Xeomin) Versus Placebo in the Treatment of Blepharospasm

Study Overview
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Brief Summary
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Patients received one injection with incobotulinumtoxinA (Xeomin) or placebo at baseline. Thereafter, all patients who entered the Open-Label Extension Period (OLEX) received up to five injection sessions of incobotulinumtoxinA (Xeomin) during the OLEX period.

Official Title
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Prospective, Double-blind, Placebo-controlled, Randomized, Multi-center Trial With an Open-label Extension Period to Investigate the Efficacy and Safety of incobotulinumtoxinA (Xeomin) in the Treatment of Blepharospasm

Conditions
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Blepharospasm

Intervention / Treatment
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* Drug: incobotulinumtoxinA (Xeomin)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Male or female pretreated outpatients between ages 18 and 80 years (inclusive) A clinical diagnosis of bilateral blepharospasm (BEB) characterized by spontaneous, spasmodic, intermittent or persistent involuntary contractions of the orbicular oculi muscles A need for injection of Botulinum toxin (defined by a Jankovic Rating Scale (JRS) severity subscore >= 2) On a stable dose of other medications (if any) used for focal dystonia treatment (e.g. anticholinergics and benzodiazepines) for at least 3 months prior to and expected throughout the Main Period Source documentation of the last two consecutive injection sessions with BOTOX® and a stable satisfactory therapeutic response directly prior to trial entry At least 10 weeks must have been passed between the last injection with BOTOX® for BEB and Baseline Main Exclusion Criteria: Atypical variant of BEB caused by inhibition of levator palpebrae muscle Myotomy or denervation surgery in the affected muscles (e.g. peripheral denervation and/or spinal cord stimulation) The previous two injections with BOTOX® with more than 50 Units per eye Hypersensitivity to human serum albumin, sucrose, or Botulinum toxin A Neuroleptic induced blepharospasm Diagnosis of myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, or any other significant neuromuscular disease which might interfere with the trial Treatment with Botulinum toxins for any indication other than BEB within 4 months prior to Baseline and during the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: incobotulinumtoxinA (Xeomin)<br>incobotulinumtoxinA (Xeomin, also known as NT 201 or Botulinum toxin type A (150 kiloDalton), free from complexing proteins) powder for solution for injection dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl), up to 50 Units per eye; Open-Label Extension Period: up to 5 injections, up to 50 Units per eye per injection session; Mode of administration: intramuscular injection | Drug: incobotulinumtoxinA (Xeomin)<br>* incobotulinumtoxinA (Xeomin, also known as NT 201 or Botulinum toxin type A (150 kiloDalton), free from complexing proteins) (active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins) powder for solution for injection, up to 50 Units per eye; Mode of administration: intramuscular injection<br>|
| Placebo Comparator: Placebo<br>Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl), placebo volume corresponding to up to 50 Units per eye; Mode of administration: intramuscular injection | Drug: Placebo<br>* Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection dose (Main Period only): one injection session of solution, prepared by reconstitution of powder with 0.9% Sodium chloride (NaCl), placebo volume corresponding to up to 50 Units per eye; Mode of administration: intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Jankovic Rating Scale (JRS) Change From Baseline in the JRS Severity Subscore at Week 6 After Injection (Assessed by a Blinded Independent Rater) | The Jankovic Rating Scale (JRS) is used for classification of the patient's individual symptoms of blepharospasm and for determination of the therapeutic efficacy of study medication. The JRS sumscore is the sum of the two components of the scale: JRS-Severity score which ranges from 0 (=absence of severity) to 4 (=maximum severity) JRS-Frequency score which ranges from 0 (=no frequency) to 4 (=maximum frequency) The change from baseline was calculated as the score at the corresponding visit minus the baseline score. | Baseline, week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Jankovic Rating Scale (JRS) Change From Baseline in the JRS Severity Subscore at Week 6 After Injection (Assessed by Subject Diary) | The Jankovic Rating Scale (JRS) is used for classification of the patient's individual symptoms of blepharospasm and for determination of the therapeutic efficacy of study medication. The JRS sumscore is the sum of the two components of the scale: JRS-Severity score which ranges from 0 (=absence of severity) to 4 (=maximum severity) JRS-Frequency score which ranges from 0 (=no frequency) to 4 (=maximum frequency) The change from baseline was calculated as the score at the corresponding visit minus the baseline score. | Baseline, week 6 | 
| Blepharospasm Disability Index (BSDI) Change From Baseline in the BSDI at Week 6 After Injection | The Blepharospasm Disability Index is a scale for the assessment of impairment of specific activities of daily living caused by blepharospasm. The BSDI consists of six items (driving a vehicle; reading; watching TV; shopping; getting about on foot (walking); doing everyday activities), each ranges from 0 (=no impairment) to 4 (=no longer possible due to illness). The change from baseline was calculated as the score at the corresponding visit minus the baseline score. | Baseline, week 6 | 
| Patient Evaluation of Global Response (PEGR) at Final Visit | The PEGR is a descriptive subjective 9-point response scale ranging from complete abolishment of signs and symptoms (value=+4) down to very marked worsening (value=-4). | Final visit (up to week 20 after injection of the Main Period) |