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

Merz Pharmaceuticals GmbH61 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Bilateral Blepharospasm (BEB)

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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. 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.

Locations (11)

Merz Investigational Site #030002

Athens, Greece

Merz Investigational Site #030001

Athens, Greece

Merz Investigational Site #060007

George Town, Pulau Pinang, Malaysia

Merz Investigational Site #060004

Kota Kinabalu, Sabah, Malaysia

Merz Investigational Site #060006

Kuala Lumpur, Malaysia

Merz Investigational Site #060002

Kuala Lumpur, Malaysia

Merz Investigational Site #060003

Kuala Selangor, Malaysia

Merz Investigational Site #094001

Colombo, Sri Lanka

Merz Investigational Site #094005

Colombo, Sri Lanka

Merz Investigational Site #094006

Kurunegala, Sri Lanka

...and 1 more locations

Outcomes

Primary Outcomes

Double-blind MP: Change From Baseline in JRS Severity Subscore at 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.

Time frame: Baseline, Day 43 (Visit 4)

Secondary Outcomes

Double-blind MP: Change From Baseline in Blepharospasm Disability Index (BSDI) at 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.

Time frame: Baseline, Day 43 (Visit 4)

Double-blind MP: Patient Evaluation of Global Response (PEGR) at 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.

Time frame: Baseline, Final Visit (Day 43-Day 141)