Study to Compare the Efficacy and Safety of NT 201 (Botulinum Toxin) With Placebo for the Treatment of Lower Limb Spasticity Caused by Stroke or Traumatic Brain Injury

NCT ID: NCT03992404

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

603 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-16

Study Completion Date

2027-04-30

Brief Summary

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The purpose of this study is to determine whether a single treatment with administration of 400 Units NT 201 (botulinum toxin) is superior to placebo (no medicine) for the treatment of lower limb spasticity caused by stroke or traumatic brain injury (Main Period). Participants will be assigned to the treatment groups by chance and neither the participants nor the research staff who interact with them will know the allocation.

The following 4 to 5 treatment cycles will investigate the safety and tolerability of treatment with NT 201 (botulinum toxin) when administered in doses between 400 and 800 Units (Open Label Extension Period). All participants will receive the treatment and the dose will depend on whether only lower limb spasticity or combined upper and lower limb spasticity are treated.

Detailed Description

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Conditions

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Lower Limb or Combined Lower Limb and Upper Limb Spasticity Due to Stroke or Traumatic Brain Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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NT 201 (IncobotulinumtoxinA, Xeomin)

Main Period (1 treatment cycle): subjects to receive intramuscular injection of NT 201 (400 units) into muscles of the lower limb.

Open Label Extension Period (4-5 treatment cycles): subjects to receive intramuscular injection of NT 201 (up to 800 units) into muscles of the lower limb and upper limb, if indicated.

Group Type EXPERIMENTAL

NT 201

Intervention Type DRUG

Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).

Placebo

Main Period (1 treatment cycle): subjects to receive intramuscular placebo injection into muscles of the lower limb.

Open Label Extension Period (4-5 treatment cycles): subjects to receive intramuscular injection of NT 201 (up to 800 units) into muscles of the lower limb and upper limb, if indicated.

Group Type PLACEBO_COMPARATOR

NT 201

Intervention Type DRUG

Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).

Placebo

Intervention Type DRUG

Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).

Interventions

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NT 201

Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).

Intervention Type DRUG

Placebo

Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).

Intervention Type DRUG

Other Intervention Names

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IncobotulinumtoxinA Incobotulinumtoxin A Xeomin Botulinum toxin type A (150 kiloDalton), free from complexing proteins

Eligibility Criteria

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Inclusion Criteria

* Female or male subject ≥ 18 years and ≤ 85 years at screening
* Diagnosis of lower limb spasticity with or without upper limb spasticity of the same body side caused by stroke or traumatic brain injury
* Disabling ankle flexor spasticity presenting as pes equinus or pes equinovarus
* Modified Ashworth Scale-Bohannon \[MAS\] score of 2 or 3 points in the ankle plantar flexor of the target lower limb (supine position, knee extended)
* Minimum passive range of motion in ankle of the target lower limb (supine position, knee extended): 10°dorsiflexion and 20°plantarflexion
* At least 4 months since last botulinum neurotoxin \[BoNT\] injection for treatment of spasticity or any other condition
* For subjects receiving anticoagulation therapy, the investigator confirms and documents that the subject has an:
* Activated partial thromboplastin time \[aPTT\] ≤ 80 seconds (subjects on dabigatran or other direct thrombin inhibitors) or
* International normalized ratio \[INR\] value of ≤ 2.5 (subjects on coumarins or other anticoagulants monitored by INR)

Exclusion Criteria

* Generalized disorders of muscle activity (e.g. myasthenia gravis, Lambert Eaton syndrome, amyotrophic lateral sclerosis) or any other significant peripheral neuromuscular dysfunction which might interfere with the study
* Bilateral lower limb paresis/paralysis/spasticity or tetraparesis/paralysis/spasticity
* Body weight \< 50 kg
* Severe atrophy of the target limb muscles
* Previous, ongoing or planned treatments of spasticity with intrathecal baclofen
* Previous, ongoing, or planned treatments of spasticity in the target lower limb with any of the following procedures: Surgical Intervention; Alcohol or phenol block; Muscle afferent block
* Physiotherapy or use of orthoses or splints at the target limb initiated less than 4 weeks before screening or expected to change during the double blind phase of the study
* Current or planned treatment with parenterally administered drugs that interfere with neuromuscular transmission (e.g. intrathecal baclofen, tubocurarine type muscle relaxants used in anesthesia), or local anesthetics in the treated region within 2 weeks prior to screening
* Infection or inflammation at the injection sites
* Subjects with presence or history of aspiration pneumonia, recurrent lower respiratory tract infections, or compromised respiratory function as per investigator's clinical judgment
* Pregnancy (as verified by a positive pregnancy test) or breast feeding
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merz Pharmaceuticals GmbH

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Merz Medical Expert

Role: STUDY_DIRECTOR

Merz Pharmaceuticals GmbH

Locations

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Physical Medicine and Rehabilitation at University of Alabama at Birmingham; Merz investigational site #0010479

Birmingham, Alabama, United States

Site Status

University of Arkansas for Medical Sciences, Merz investigational site #0010481

Little Rock, Arkansas, United States

Site Status

Rancho Research Institute at Rancho Los Amigos National Rehabilitation Center; Merz investigational site #0010184

Downey, California, United States

Site Status

New England institute for clinical research; Merz Investigational Site #0010441

Stamford, Connecticut, United States

Site Status

Nova Clinical Research, Merz investigational site #0010474

Brandenton, Florida, United States

Site Status

Brooks Rehabilitation Clinical Integration and Research, Merz investigational site #0010483

Jacksonville, Florida, United States

Site Status

Sarasota Memorial Health Care System, Rehabilitation Medicine, Merz investigational site #0010478

Sarasota, Florida, United States

Site Status

Neurology Center of New England P.C., Merz investigative site #0010476

Foxborough, Massachusetts, United States

Site Status

Howard A. Rusk Rehabilitation Center; Merz investigational site #0010283

Columbia, Missouri, United States

Site Status

Icahn School of Medicine at Mount Sinai, Neurology Department, Merz Investigational Site #0010191

New York, New York, United States

Site Status

Weill Cornell Medical Center, Department of Rehabilitation Medicine; Merz Investigational Site #0010440

New York, New York, United States

Site Status

University of Pittsburgh Medical Center, Physical Medicine & Rehabiliation, Merz Investigational Site #0010211

Pittsburgh, Pennsylvania, United States

Site Status

UT Southwestern Medical Center, Department of Physical Medicine & Rehabilitation, Merz investigational site #0010082

Dallas, Texas, United States

Site Status

University of Texas Health Science Center McGovern, Medical School Department of PM&R; merz investigational site #0010183

Houston, Texas, United States

Site Status

Medical College of Wisconsin,Department of PM&R, Merz Investigational Site #0010237

Milwaukee, Wisconsin, United States

Site Status

CHU Brugmann Neurology; Merz investigational site #0320015

Brussels, , Belgium

Site Status

UCL Bruxelles, Physical Medicine & Rehabilitation Department, Merz Investigational Site #0320013

Brussels, , Belgium

Site Status

UZ Leuven Pellenberg campus; Merz investigational site #0320014

Pellenberg, , Belgium

Site Status

UCL Mont Godinne, Physical Medicine & Rehabilitation Department; Merz Investigational Site #0320008

Yvoir, , Belgium

Site Status

Glenrose Rehabilitation Hospital, Merz investigational site #0010195

Edmonton, , Canada

Site Status

Neurology and Physiotherapy Skopalikova, Merz Investigational Site #4200049

Brno, , Czechia

Site Status

University Hospital Ostrava; Neurology Departement, Merz investigational site #4200024

Ostrava, , Czechia

Site Status

Pardubice Regional Hospital; Merz investigational site #4200025

Pardubice, , Czechia

Site Status

Raymond Poincaré University Hospital, Service de MPR Pôle Handicap-Rééducation, Merz Investigational site #00330018

Garches, , France

Site Status

CHU Lille/Hôpital Swynghedauw; investigational site # 0330045

Lille, , France

Site Status

Pôle Saint-Hélier; Merz investigational site #0330024

Rennes, , France

Site Status

Institut Universitaire de Readaptation Clemenceau, Physical Medicine / Rehabilitation Medecine, Merz Investigational site # 0330063

Strasbourg, , France

Site Status

Rangueil Hospital-University Hospital Center (CHU) of Toulouse, Médecine physique et de réadaptation, Merz investigational site #0330025

Toulouse, , France

Site Status

Uniklinik RWTH Aachen, Neurologie, Merz Investigational Site #0490191

Aachen, , Germany

Site Status

Neurologie Bewegt; Merz Investigational site #0490378

Berlin, , Germany

Site Status

University of Bonn Medical Center, Department of Neurodegenerative disease, Merz investigational site #0490390

Bonn, , Germany

Site Status

Heinrich Heine University Duesseldorf, Department of Neurology; Merz Investigational Site #0490071

Düsseldorf, , Germany

Site Status

Universitätsklinikum Hamburg-Eppendorf, Merz Investigational site #0490079

Hamburg, , Germany

Site Status

DKD HELIOS Medical Center, Fachbereich Neurologie, Merz Investigational Site #0490081

Wiesbaden, , Germany

Site Status

Neurologische Klinik und Poliklinik des Universitätsklinikums Würzburg, Merz Investigational Site #0490302

Würzburg, , Germany

Site Status

Petz Hospital, Neurology, Merz Investigational Site #0360010

Győr, , Hungary

Site Status

St.Damjan Hospital, Kisvarda; Merz investigational site #0360019

Kisvárda, , Hungary

Site Status

University of Szeged, Department of Neurology, Merz investigational site #0360008

Szeged, , Hungary

Site Status

Azienda Ospedaliera Universitaria Ospedali Riuniti Di Foggia; Merz Investigational Site #0390018

Foggia, , Italy

Site Status

IRCCS Ospedale Policlinico S. Martino, U.O.Complessa Riabilitazione e Rieducazione Funzionale; Merz investigational site #0390020

Genova, , Italy

Site Status

Ospedale Maggiore della Carita, Dipartimento di Medicina fisica e Riabilitativa, Merz Investigational Site #0390017

Novara, , Italy

Site Status

Ospedale Alfredo Fiorini, UOSD Neurologia Universitaria; Merz Investigational site #0390022

Terracina, , Italy

Site Status

Specjalistyczna Praktyka Lekarska Dr. n. med Stanisław Ochudło, Merz Investigational Site #0480077

Katowice, , Poland

Site Status

Specjalistyczne Gabinety Sp z o.o., Merz Investigational Site #0480059

Krakow, , Poland

Site Status

NeuroKlinika Gabinet Lekarski Prof Andrzej Bogucki, Merz Investigational Site #0480101

Lodz, , Poland

Site Status

Indywidualna Praktyka Lekarska dr. hab. Med. Anna Szczepanska-Szerej, Merz Investigational Site #0480096

Lublin, , Poland

Site Status

Filia 7 Centrum Kompleksowej Rehabilitacji Sp. z o.o., Merz Investigational Site #0480100

Warsaw, , Poland

Site Status

Projekt Samodzielni Sp z o.o., Merz Investigational Site #0480099

Warsaw, , Poland

Site Status

Instytut Psychiatrii i Neurologii, II Klinika Neurologiczna, Merz Investigational Site #0480023

Warsaw, , Poland

Site Status

Mazowiecki Szpital Brodnowski, Merz investigational site #0480064

Warsaw, , Poland

Site Status

Neuryt Diagnostyka I Terapia Neurologiczna, Merz investigational site #0480106

Wroclaw, , Poland

Site Status

Federal State Budgetary Educational Institution of Higher Education "Krasnoyarsk State Medical University n.a. Professor V.F. Voino-Yasenetskiy of Ministry Healthcare of Russian Federation", Merz Investigational Site #0070306

Krasnoyarsk, , Russia

Site Status

State Autonomous Institution of Healthcare of Moscow City "Moscow Scientific and Practical Centre of Medical Rehabilitation, Regenerative and Sports Medicine of Moscow City Healthcare Department", Merz Investigational Site #0070011

Moscow, , Russia

Site Status

Federal State Autonomous Institution "National Medical Research Centre "Treatment and Rehabilitation" of the Ministry of Health of the Russian Federation, Neurology department, Merz Investigational Site # 0070305

Moscow, , Russia

Site Status

Federal State Budgetary Institution "National Medical Research Centre of Psychiatry and Neurology n.a. V.M. Bekhterev" of the Ministry of Healthcare of the Russian Federation, Merz Investigational Site #0070009

Saint Petersburg, , Russia

Site Status

University Hospital Bratislav, 2nd Dept. of Neurology, Merz Investigational Site # 4210005

Bratislava, , Slovakia

Site Status

Neurologicka klinika, Fakultna nemocnica Trnava; Merz investigational site #4210009

Trnava, , Slovakia

Site Status

Hospital Universitario Juan Ramón Jiménez, Merz Investigational Site #0340037

Huelva, , Spain

Site Status

Hospital Universitario La Paz, Merz Investigational Site #0340007

Madrid, , Spain

Site Status

Hospital Universitari Mútua de Terrassa, Merz Investigational Site #0340003

Terrassa, , Spain

Site Status

University Hospital of Bern, Center of Parkinson's diseases and Movement disorders (ZfPB), Merz investigational site #0410015

Bern, , Switzerland

Site Status

HFR Fribourg - Hôpital Cantonal, Department of Rehabilitation, Merz Investigational site #0410014

Meyriez, , Switzerland

Site Status

CRR, Mee Suva (Clinique romande de réadaptation), Merz investigational site #0410016

Sion, , Switzerland

Site Status

Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine, MC "Neuron", Merz Investigational Site #3800018

Kharkiv, , Ukraine

Site Status

Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine; Merz Investigational Site #3800019

Kharkiv, , Ukraine

Site Status

Lviv regional clinical hospital; Merz investigational site # 3800020

Lviv, , Ukraine

Site Status

Rivne City Hospital 2, Department of Clinical Neurology and Neurorehabilitation; Merz investigational site #3800016

Rivne, , Ukraine

Site Status

NPE "Regional Clinical Centre of Neurosurgery and Neurology" Transcarpathian Regional Council; Merz investigational site #3800014

Uzhhorod, , Ukraine

Site Status

Cambridge University Hospitals NHS Foundation Trust; Merz Investigational Site 0440023

Cambridge, , United Kingdom

Site Status

Royal Devon and Exeter Foundation Trust Hospital, Department of Neurology, Merz Investigational Site #0440047

Exeter, , United Kingdom

Site Status

The Walton Centre NHS Foundation Trust; Neuroscience Research Centre; Merz Investigational site #0440004

Liverpool, , United Kingdom

Site Status

Countries

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Australia Norway United States Belgium Canada Czechia France Germany Hungary Italy Poland Russia Slovakia Spain Switzerland Ukraine United Kingdom

Other Identifiers

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2018-001639-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M602011014

Identifier Type: -

Identifier Source: org_study_id