Clinical trial NCT01896895: Efficacy and Safety Study of Botulinum Toxin Type A Against Placebo to Treat Abnormal Contraction or Twitch of the Eyelid
Official title: Prospective, Double-blind, Placebo-controlled, Randomized, Parallel-group, Multi-center Study With an Open-label Extension Period to Investigate the Efficacy and Safety of Two Different Doses of NT 201 in Botulinum Toxin Treatment-naïve Subjects With Blepharospasm
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bilateral Blepharospasm (BEB)
Lead sponsor: Merz Pharmaceuticals GmbH
Sponsor class: INDUSTRY
First posted: 2013-07-11
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Double-blind MP: Change From Baseline in JRS Severity Subscore at Day 43 (Visit 4)
timeFrame: Baseline, Day 43 (Visit 4)
Secondary outcomes:
measure: Double-blind MP: Change From Baseline in Blepharospasm Disability Index (BSDI) at Day 43 (Visit 4)
timeFrame: Baseline, Day 43 (Visit 4)
measure: Double-blind MP: Patient Evaluation of Global Response (PEGR) at Final Visit (Day 43-Day 141)
timeFrame: Baseline, Final Visit (Day 43-Day 141)
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Merz Investigational Site #030002
city: Athens
country: Greece
facility: Merz Investigational Site #030001
city: Georgetown
country: Malaysia
facility: Merz Investigational Site #060007
state: Penang
city: Kota Kinabalu
country: Malaysia
facility: Merz Investigational Site #060004
state: Sabah
city: Kuala Lumpur
country: Malaysia
facility: Merz Investigational Site #060006
city: Kuala Lumpur
country: Malaysia
facility: Merz Investigational Site #060002
city: Selangor
country: Malaysia
facility: Merz Investigational Site #060003
city: Colombo
country: Sri Lanka
facility: Merz Investigational Site #094001
city: Colombo
country: Sri Lanka
facility: Merz Investigational Site #094005
city: Kurunegala
country: Sri Lanka
facility: Merz Investigational Site #094006
city: Nugegoda
country: Sri Lanka
facility: Merz Investigational Site #094002
Study officials:
affiliation: Merz Pharmaceuticals GmbH
name: Merz Medical Expert
role: STUDY_DIRECTOR
References:
citation: Mitsikostas DD, Dekundy A, Hanschmann A, Althaus M, Scheschonka A, Pagan F, Jankovic J. Duration and onset of effect of incobotulinumtoxinA for the treatment of blepharospasm in botulinum toxin-naive subjects. Curr Med Res Opin. 2021 Oct;37(10):1761-1768. doi: 10.1080/03007995.2021.1965975. Epub 2021 Aug 24.
citation: Duarte GS, Rodrigues FB, Marques RE, Castelao M, Ferreira J, Sampaio C, Moore AP, Costa J. Botulinum toxin type A therapy for blepharospasm. Cochrane Database Syst Rev. 2020 Nov 19;11(11):CD004900. doi: 10.1002/14651858.CD004900.pub3.
citation: Mitsikostas DD, Dekundy A, Sternberg K, Althaus M, Pagan F. IncobotulinumtoxinA for the Treatment of Blepharospasm in Toxin-Naive Subjects: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Trial. Adv Ther. 2020 Oct;37(10):4249-4265. doi: 10.1007/s12325-020-01427-6. Epub 2020 Aug 10.