Efficacy and Safety Study of Botulinum Toxin Type A Against Placebo to Treat Abnormal Contraction or Twitch of the Eyelid

Phase 3

Completed

• Conditions: Bilateral Blepharospasm (BEB)
• Interventions: Drug: IncobotulinumtoxinA (Xeomin), 12.5 Units; Drug: IncobulinumtoxinA (Xeomin), 25 Units; Drug: Placebo; Drug: IncobotulinumtoxinA (Xeomin), 35 Units

• Registration Number: NCT01896895
• Lead Sponsor: Merz Pharmaceuticals GmbH

Brief Summary

This phase 3 study will serve to collect efficacy and safety data of two different doses of NT 201 in subjects suffering from Bilateral Blepharospasm (BEB) who are BTX treatment-naïve.

In this study, BTX treatment-naïve subjects are defined as those who have not received BTX treatment within the last 12 months for the treatment of BEB. This definition aims to avoid bias by comparison of treatment effects in the subject's assessments. Furthermore, this study will substantiate the existing efficacy and safety database for the indication BEB.

Detailed Description

Subjects to receive one injection with NT 201 or placebo at baseline of the placebo-controlled first cycle. Thereafter, all subjects entering the Open-Label Extension Period (OLEX) to receive a second injection of NT 201 (second injection cycle).

Study Timeline

• Study First Submitted: 2013-07-08
• Study First Submitted QC: 2013-07-08
• Study First Posted: 2013-07-11
• Study Start: 2013-11
• Primary Completion: 2016-04
• Study Completion: 2016-11
• Disposition First Submitted: 2017-03-30
• Disposition First Submitted QC: 2017-03-30
• Disposition First Posted: 2017-03-31
• Status Verified: 2018-01
• Results First Submitted: 2018-01-08
• Results First Submitted QC: 2018-02-28
• Last Update Submitted: 2018-02-28
• Results First Posted: 2018-03-01
• Last Update Posted: 2018-03-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 61

Inclusion Criteria

• Male or female out-patients age ≥ 18 and ≤ 80 years.
• A clinical diagnosis of bilateral BEB characterized by spontaneous, spasmodic, intermittent or persistent involuntary contractions of orbicular oculi muscles.
• A need for injection of BTX defined as a Jankovic Rating Scale [JRS] severity subscore ≥ 2.
• Treatment-naïve subject defined as at least 12 months without BTX of any serotype for the treatment of BEB before administration of IP.

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Exclusion Criteria

• Subject with any previous unsuccessful treatment with BTX of any serotype for the treatment of BEB.
• Atypical variant of BEB (e.g., apraxia of the eyelid opening) caused by inhibition of levator palpebrae muscle.
• Neuroleptic-induced blepharospasm.
• Myotomy or denervation surgery in the affected muscles (e.g., peripheral denervation, spinal cord stimulation) and surgery in the upper face.
• Generalized disorders of muscles activity (e.g., myasthenia gravis in particular ocularis, Lambert-Eaton-Syndrome, amyotrophic lateral sclerosis) or any other significant neuromuscular dysfunction which might interfere with the study.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	IncobotulinumtoxinA (Xeomin), 35 Units	Main Period: Placebo to IncobotulinumtoxinA (Xeomin)(12.5 or 25U/eye), one injection session. Open-Label Extension: IncobotulinumtoxinA (Xeomin), one injection session, up to 35 Units per eye. Mode of administration: intramuscular injection.
IncobotulinumtoxinA (Xeomin) 12.5U per eye	IncobotulinumtoxinA (Xeomin), 12.5 Units	Main Period: one injection session, 12.5 Units per eye. Open-Label Extension Period: one injection session, up to 35 Units per eye. Mode of administration: intramuscular injection.
IncobotulinumtoxinA (Xeomin) 12.5U per eye	IncobotulinumtoxinA (Xeomin), 35 Units	Main Period: one injection session, 12.5 Units per eye. Open-Label Extension Period: one injection session, up to 35 Units per eye. Mode of administration: intramuscular injection.
IncobotulinumtoxinA (Xeomin) 25U per eye	IncobulinumtoxinA (Xeomin), 25 Units	Main Period: one injection session, 25 Units per eye. Open-Label Extension: one injection session, up to 35 Units per eye. Mode of administration: intramuscular injection.
IncobotulinumtoxinA (Xeomin) 25U per eye	IncobotulinumtoxinA (Xeomin), 35 Units	Main Period: one injection session, 25 Units per eye. Open-Label Extension: one injection session, up to 35 Units per eye. Mode of administration: intramuscular injection.
Placebo	Placebo	Main Period: Placebo to IncobotulinumtoxinA (Xeomin)(12.5 or 25U/eye), one injection session. Open-Label Extension: IncobotulinumtoxinA (Xeomin), one injection session, up to 35 Units per eye. Mode of administration: intramuscular injection.

Primary Outcome Measures

Name	Time	Method
Double-blind MP: Change From Baseline in JRS Severity Subscore at Day 43 (Visit 4)	Baseline, Day 43 (Visit 4)	JRS severity subscore was used to classify individual symptoms of blepharospasm and to determine therapeutic efficacy. JRS severity subscore ranges from 0 to 4, where 0: None; 1: increased blinking present with external stimuli; 2: Mild but spontaneous eyelid fluttering, definitely noticeable, possibly embarrassing, but not functionally disabling, 3: Moderate, very noticeable spasm of eyelids only, mildly incapacitating, 4: Severe, incapacitating spasm of eyelids and possibly other facial muscles. Values represent least square (LS) mean differences between baseline and visit 4 resulting from analysis of covariance (ANCOVA) with treatment group, pooled site, and gender as fixed factors and baseline JRS severity subscore and age as covariates and missings replaced using the last observation carried forward (LOCF) method. Negative values denote improvement, while positive values denote deterioration vs. baseline.

Secondary Outcome Measures

Name	Time	Method
Double-blind MP: Patient Evaluation of Global Response (PEGR) at Final Visit (Day 43-Day 141)	Baseline, Final Visit (Day 43-Day 141)	PEGR scale is a descriptive subjective 9-point response self-rating scale ranging from "complete abolishment of signs and symptoms" (value=+4) down to "very marked worsening" (value=-4). Outcome values represent least square means at visit 4 resulting from an ANCOVA with treatment group, pooled site, gender as fixed factors and age as covariates. Missing were set to a zero effect (value=0). Positive values denote an improvement, while negative values denote deterioration.
Double-blind MP: Change From Baseline in Blepharospasm Disability Index (BSDI) at Day 43 (Visit 4)	Baseline, Day 43 (Visit 4)	BSDI is a scale for assessment of impairment of specific activities of daily living caused by blepharospasm. BSDI consists of six items (driving a vehicle; reading; watching TV; shopping; getting about on foot (walking); doing everyday activities), each ranging from 0 (=no impairment) to 4 (=no longer possible due to illness). The BSDI total score is a mean score for non-missing items ranging from 0 to 4. It is calculated by adding scores of all applicable and answered items, and dividing the resulting sum by the number of items answered. Outcome values represent LS mean differences between baseline and visit 4 (visit 4 value minus baseline value) resulting from ANCOVA with treatment group, pooled site, gender as fixed factors and baseline BSDI total score, age as covariates. Missings were replaced by the LOCF method. Negative values denote an improvement, while positive values denote deterioration vs. baseline.

Trial Locations

Locations (11)

Merz Investigational Site #094001; 🇱🇰 Colombo, Sri Lanka

Merz Investigational Site #094006; 🇱🇰 Kurunegala, Sri Lanka

Merz Investigational Site #030002; 🇬🇷 Athens, Greece

Merz Investigational Site #060007; 🇲🇾 Georgetown, Penang, Malaysia

Merz Investigational Site #060003; 🇲🇾 Selangor, Malaysia

Merz Investigational Site #094002; 🇱🇰 Nugegoda, Sri Lanka

Merz Investigational Site #030001; 🇬🇷 Athens, Greece

Merz Investigational Site #060006; 🇲🇾 Kuala Lumpur, Malaysia

Merz Investigational Site #060004; 🇲🇾 Kota Kinabalu, Sabah, Malaysia

Merz Investigational Site #060002; 🇲🇾 Kuala Lumpur, Malaysia

Merz Investigational Site #094005; 🇱🇰 Colombo, Sri Lanka