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

NCT03992404 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: M6020110142018-001639-35
• Study Type: interventional
• Target: 603
• Locations: 15 countries
• Sites: 71

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Change from baseline in derived Modified Ashworth Scale-Bohannon (MAS) ankle score (knee extended) at weeks 4 to 6

  The MAS is a 6-grade scale

  Baseline to week 4-6

• Co-Primary: Global Impression of Change Scale (GICS) assessed by physician at Week 4 to 6

  The GICS s a 9-grade scale

  Week 4-6

• Occurrence of treatment emergent adverse events [TEAEs] in the Main Period

  Baseline to week 12

Secondary Outcomes (3)

• Change from Study Baseline in Goal Attainment Scale [GAS] at Week 6

  Baseline to week 6

• Global Impression of Change Scale (GICS) assessed by the study subject at Week 4 to 6

  Week 4-6

• Global Impression of Change Scale (GICS) assessed by the caregiver at Week 4 to 6

  Week 4-6

Study Arms (2)

NT 201 (IncobotulinumtoxinA, Xeomin)

EXPERIMENTAL

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.

Drug: NT 201

Placebo

PLACEBO COMPARATOR

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.

Drug: NT 201; Drug: Placebo

Interventions

NT 201 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).

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

NT 201 (IncobotulinumtoxinA, Xeomin); Placebo

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Merz Pharmaceuticals GmbH: lead

Study Sites (71)

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

Birmingham, Alabama, 35233, United States

Location

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

Little Rock, Arkansas, 72205, United States

Location

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

Downey, California, 90242, United States

Location

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

Stamford, Connecticut, 06905, United States

Location

Nova Clinical Research, Merz investigational site #0010474

Brandenton, Florida, 34209, United States

Location

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

Jacksonville, Florida, 72204, United States

Location

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

Sarasota, Florida, 34239, United States

Location

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

Foxborough, Massachusetts, 02035, United States

Location

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

Columbia, Missouri, 65203, United States

Location

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

New York, New York, 10029, United States

Location

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

New York, New York, 10065, United States

Location

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

Pittsburgh, Pennsylvania, 15213, United States

Location

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

Dallas, Texas, 75390-9055, United States

Location

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

Houston, Texas, 77030, United States

Location

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

Milwaukee, Wisconsin, 53226, United States

Location

CHU Brugmann Neurology; Merz investigational site #0320015

Brussels, 1020, Belgium

Location

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

Brussels, 1200, Belgium

Location

UZ Leuven Pellenberg campus; Merz investigational site #0320014

Pellenberg, 3212, Belgium

Location

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

Yvoir, 5530, Belgium

Location

Glenrose Rehabilitation Hospital, Merz investigational site #0010195

Edmonton, T5G 0B7, Canada

Location

Neurology and Physiotherapy Skopalikova, Merz Investigational Site #4200049

Brno, 61500, Czechia

Location

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

Ostrava, 708 52, Czechia

Location

Pardubice Regional Hospital; Merz investigational site #4200025

Pardubice, 530 03, Czechia

Location

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

Garches, 92380, France

Location

CHU Lille/Hôpital Swynghedauw; investigational site # 0330045

Lille, 59000, France

Location

Pôle Saint-Hélier; Merz investigational site #0330024

Rennes, 35000, France

Location

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

Strasbourg, 67000, France

Location

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

Toulouse, 31059, France

Location

Uniklinik RWTH Aachen, Neurologie, Merz Investigational Site #0490191

Aachen, 52074, Germany

Location

Neurologie Bewegt; Merz Investigational site #0490378

Berlin, 10627, Germany

Location

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

Bonn, 53127, Germany

Location

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

Düsseldorf, 40225, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, Merz Investigational site #0490079

Hamburg, 20246, Germany

Location

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

Wiesbaden, 65191, Germany

Location

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

Würzburg, 97080, Germany

Location

Petz Hospital, Neurology, Merz Investigational Site #0360010

Győr, 9024, Hungary

Location

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

Kisvárda, 4600, Hungary

Location

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

Szeged, 6725, Hungary

Location

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

Foggia, 71122, Italy

Location

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

Genova, 16132, Italy

Location

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

Novara, 28100, Italy

Location

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

Terracina, 04019, Italy

Location

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

Katowice, 40-097, Poland

Location

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

Krakow, 30-539, Poland

Location

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

Lodz, 90-640, Poland

Location

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

Lublin, 20-582, Poland

Location

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

Warsaw, 01-518, Poland

Location

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

Warsaw, 02-121, Poland

Location

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

Warsaw, 02-957, Poland

Location

Mazowiecki Szpital Brodnowski, Merz investigational site #0480064

Warsaw, 03-242, Poland

Location

Neuryt Diagnostyka I Terapia Neurologiczna, Merz investigational site #0480106

Wroclaw, 50-305, Poland

Location

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, 660049, Russia

Location

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, 105005, Russia

Location

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, 125367, Russia

Location

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, 195119, Russia

Location

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

Bratislava, 83305, Slovakia

Location

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

Trnava, 917 01, Slovakia

Location

Hospital Universitario Juan Ramón Jiménez, Merz Investigational Site #0340037

Huelva, 21005, Spain

Location

Hospital Universitario La Paz, Merz Investigational Site #0340007

Madrid, 28046, Spain

Location

Hospital Universitari Mútua de Terrassa, Merz Investigational Site #0340003

Terrassa, 08221, Spain

Location

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

Bern, 3010, Switzerland

Location

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

Meyriez, 3280, Switzerland

Location

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

Sion, 1950, Switzerland

Location

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

Kharkiv, 61000, Ukraine

Location

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

Kharkiv, 61000, Ukraine

Location

Lviv regional clinical hospital; Merz investigational site # 3800020

Lviv, 79010, Ukraine

Location

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

Rivne, 33001, Ukraine

Location

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

Uzhhorod, 88018, Ukraine

Location

Cambridge University Hospitals NHS Foundation Trust; Merz Investigational Site 0440023

Cambridge, CB2 0QQ, United Kingdom

Location

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

Exeter, EX2 5DW, United Kingdom

Location

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

Liverpool, L9 7LJ, United Kingdom

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

incobotulinumtoxinA; Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Study Officials

• Merz Medical Expert

  Merz Pharmaceuticals GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: June 20, 2019
• Study Start: September 16, 2019
• Primary Completion: June 19, 2025
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); HU (3); CZ (3); IT (4); CH (3); ES (3); DE (7); PL (9); BE (4); RU (4); FR (5); US (15); CA (1); UA (5); SL (2)