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

Phase 3

Recruiting

• Conditions: Lower Limb or Combined Lower Limb and Upper Limb Spasticity Due to Stroke or Traumatic Brain Injury
• Interventions: Drug: NT 201; Drug: Placebo

• Registration Number: NCT03992404
• Lead Sponsor: Merz Pharmaceuticals GmbH

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-06-18
• Study First Submitted QC: 2019-06-18
• Study First Posted: 2019-06-20
• Study Start: 2019-09-16
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-23
• Last Update Posted: 2024-12-27
• Primary Completion: 2025-08
• Study Completion: 2027-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 600

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	NT 201	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.
NT 201 (IncobotulinumtoxinA, Xeomin)	NT 201	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.
Placebo	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.

Primary Outcome Measures

Name	Time	Method
Change from baseline in derived Modified Ashworth Scale-Bohannon (MAS) ankle score (knee extended) at weeks 4 to 6	Baseline to week 4-6	The MAS is a 6-grade scale
Co-Primary: Global Impression of Change Scale (GICS) assessed by physician at Week 4 to 6	Week 4-6	The GICS s a 9-grade scale
Occurrence of treatment emergent adverse events [TEAEs] in the Main Period	Baseline to week 12

Secondary Outcome Measures

Name	Time	Method
Global Impression of Change Scale (GICS) assessed by the study subject at Week 4 to 6	Week 4-6	The GICS s a 9-grade scale
Global Impression of Change Scale (GICS) assessed by the caregiver at Week 4 to 6	Week 4-6	The GICS s a 9-grade scale
Change from Study Baseline in Goal Attainment Scale [GAS] at Week 6	Baseline to week 6	The GAS is a 6-grade scale

Trial Locations

Locations (81)

Brooks Rehabilitation Clinical Integration and Research, Merz investigational site #0010483; 🇺🇸 Jacksonville, Florida, United States

Physical Medicine and Rehabilitation at University of Alabama at Birmingham; Merz investigational site #0010479; 🇺🇸 Birmingham, Alabama, United States

University of Arkansas for Medical Sciences, Merz investigational site #0010481; 🇺🇸 Little Rock, Arkansas, United States

Rancho Research Institute at Rancho Los Amigos National Rehabilitation Center; Merz investigational site #0010184; 🇺🇸 Downey, California, United States

New England institute for clinical research; Merz Investigational Site #0010441; 🇺🇸 Stamford, Connecticut, United States

Nova Clinical Research, Merz investigational site #0010474; 🇺🇸 Brandenton, Florida, United States

Sarasota Memorial Health Care System, Rehabilitation Medicine, Merz investigational site #0010478; 🇺🇸 Sarasota, Florida, United States

Neurology Center of New England P.C., Merz investigative site #0010476; 🇺🇸 Foxborough, Massachusetts, United States

Howard A. Rusk Rehabilitation Center; Merz investigational site #0010283; 🇺🇸 Columbia, Missouri, United States

Rehabilitation Hospital, Kessler Institute for Rehabilitation, Merz Investigational Site #0010199; 🇺🇸 West Orange, New Jersey, United States

Icahn School of Medicine at Mount Sinai, Neurology Department, Merz Investigational Site #0010191; 🇺🇸 New York, New York, United States

Weill Cornell Medical Center, Department of Rehabilitation Medicine; Merz Investigational Site #0010440; 🇺🇸 New York, New York, United States

University of Pittsburgh Medical Center, Physical Medicine & Rehabiliation, Merz Investigational Site #0010211; 🇺🇸 Pittsburgh, Pennsylvania, United States

UT Southwestern Medical Center, Department of Physical Medicine & Rehabilitation, Merz investigational site #0010082; 🇺🇸 Dallas, Texas, United States

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

Medical College of Wisconsin,Department of PM&R, Merz Investigational Site #0010237; 🇺🇸 Milwaukee, Wisconsin, United States

St George Hospital, Department of Rehabilitation Medicine, Merz Investigational Site #0610004; 🇦🇺 Kogarah, Australia

Royal Melbourne Hospital, Department of Rehabilitation Medicine; Merz Investigational Site #0610002; 🇦🇺 Parkville, Australia

CHU Brugmann Neurology; Merz investigational site #0320015; 🇧🇪 Brussel, Belgium

UCL Bruxelles, Physical Medicine & Rehabilitation Department, Merz Investigational Site #0320013; 🇧🇪 Bruxelles, Belgium

UZ Leuven Pellenberg campus; Merz investigational site #0320014; 🇧🇪 Pellenberg, Belgium

UCL Mont Godinne, Physical Medicine & Rehabilitation Department; Merz Investigational Site #0320008; 🇧🇪 Yvoir, Belgium

Glenrose Rehabilitation Hospital, Merz investigational site #0010195; 🇨🇦 Edmonton, Canada

Neurology and Physiotherapy Skopalikova, Merz Investigational Site #4200049; 🇨🇿 Brno, Czechia

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

Pardubice Regional Hospital; Merz investigational site #4200025; 🇨🇿 Pardubice, Czechia

Fakultni nemocnice Kralovske Vinohrady, Neurology Department, Merz Investigational Site #4200050; 🇨🇿 Prague, Czechia

Raymond Poincaré University Hospital, Service de MPR Pôle Handicap-Rééducation, Merz Investigational site #00330018; 🇫🇷 Garches, France

CHU Lille/Hôpital Swynghedauw; investigational site # 0330045; 🇫🇷 Lille, France

Pôle Saint-Hélier; Merz investigational site #0330024; 🇫🇷 Rennes, France

Institut Universitaire de Readaptation Clemenceau, Physical Medicine / Rehabilitation Medecine, Merz Investigational site # 0330063; 🇫🇷 Strasbourg, France

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

Uniklinik RWTH Aachen, Neurologie, Merz Investigational Site #0490191; 🇩🇪 Aachen, Germany

Neurologie Bewegt; Merz Investigational site #0490378; 🇩🇪 Berlin, Germany

University of Bonn Medical Center, Department of Neurodegenerative disease, Merz investigational site #0490390; 🇩🇪 Bonn, Germany

Heinrich Heine University Duesseldorf, Department of Neurology; Merz Investigational Site #0490071; 🇩🇪 Düsseldorf, Germany

Universitätsklinikum Hamburg-Eppendorf, Merz Investigational site #0490079; 🇩🇪 Hamburg, Germany

CBBM, Institut für Neurogenetik, Haus 66; Merz Investigational Site #0490332; 🇩🇪 Lübeck, Germany

DKD HELIOS Medical Center, Fachbereich Neurologie, Merz Investigational Site #0490081; 🇩🇪 Wiesbaden, Germany

Neurologische Klinik und Poliklinik des Universitätsklinikums Würzburg, Merz Investigational Site #0490302; 🇩🇪 Würzburg, Germany

Petz Hospital, Neurology, Merz Investigational Site #0360010; 🇭🇺 Győr, Hungary

St.Damjan Hospital, Kisvarda; Merz investigational site #0360019; 🇭🇺 Kisvárda, Hungary

University of Szeged, Department of Neurology, Merz investigational site #0360008; 🇭🇺 Szeged, Hungary

Ospedale Valduce, Villa Beretta Rehabilitation Center, Merz investigational site #0390005; 🇮🇹 Costa Masnaga, Italy

Azienda Ospedaliera Universitaria Ospedali Riuniti Di Foggia; Merz Investigational Site #0390018; 🇮🇹 Foggia, Italy

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

Ospedale Maggiore della Carita, Dipartimento di Medicina fisica e Riabilitativa, Merz Investigational Site #0390017; 🇮🇹 Novara, Italy

Ospedale Alfredo Fiorini, UOSD Neurologia Universitaria; Merz Investigational site #0390022; 🇮🇹 Terracina, Italy

AOUI -Ospedale Borgo Roma, U.O.C Neuroriabilitazione, Merz Investigational Site #0390014; 🇮🇹 Verona, Italy

Haukeland University Hospital, Dept of Neurology; Merz investigational site #0470001; 🇳🇴 Bergen, Norway

Sunnaas Rehabilitation Hospital, Merz Investigational Site #0470002; 🇳🇴 Bjornemyr, Norway

Specjalistyczna Praktyka Lekarska Dr. n. med Stanisław Ochudło, Merz Investigational Site #0480077; 🇵🇱 Katowice, Poland

Specjalistyczne Gabinety Sp z o.o., Merz Investigational Site #0480059; 🇵🇱 Krakow, Poland

NeuroKlinika Gabinet Lekarski Prof Andrzej Bogucki, Merz Investigational Site #0480101; 🇵🇱 Lodz, Poland

Indywidualna Praktyka Lekarska dr. hab. Med. Anna Szczepanska-Szerej, Merz Investigational Site #0480096; 🇵🇱 Lublin, Poland

Filia 7 Centrum Kompleksowej Rehabilitacji Sp. z o.o., Merz Investigational Site #0480100; 🇵🇱 Warsaw, Poland

Projekt Samodzielni Sp z o.o., Merz Investigational Site #0480099; 🇵🇱 Warsaw, Poland

Instytut Psychiatrii i Neurologii, II Klinika Neurologiczna, Merz Investigational Site #0480023; 🇵🇱 Warsaw, Poland

Mazowiecki Szpital Brodnowski, Merz investigational site #0480064; 🇵🇱 Warsaw, Poland

Neuryt Diagnostyka I Terapia Neurologiczna, Merz investigational site #0480106; 🇵🇱 Wroclaw, Poland

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, Russian Federation

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, Russian Federation

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, Russian Federation

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, Russian Federation

University Hospital Bratislav, 2nd Dept. of Neurology, Merz Investigational Site # 4210005; 🇸🇰 Bratislava, Slovakia

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

Hospital Universitario Juan Ramón Jiménez, Merz Investigational Site #0340037; 🇪🇸 Huelva, Spain

Hospital Universitario La Paz, Merz Investigational Site #0340007; 🇪🇸 Madrid, Spain

Hospital Universitari Mútua de Terrassa, Merz Investigational Site #0340003; 🇪🇸 Terrassa, Spain

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

Centre Hospitalier Universitaire Vaudois - Neurorehabilitation and Physical Medicine, Merz Investigational Site #0410013; 🇨🇭 Lausanne, Switzerland

HFR Fribourg - Hôpital Cantonal, Department of Rehabilitation, Merz Investigational site #0410014; 🇨🇭 Meyriez, Switzerland

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

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

Lviv regional clinical hospital; Merz investigational site # 3800020; 🇺🇦 Lviv, Ukraine

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

NPE "Regional Clinical Centre of Neurosurgery and Neurology" Transcarpathian Regional Council; Merz investigational site #3800014; 🇺🇦 Uzhgorod, Ukraine

Cambridge University Hospitals NHS Foundation Trust; Merz Investigational Site 0440023; 🇬🇧 Cambridge, United Kingdom

Royal Devon and Exeter Foundation Trust Hospital, Department of Neurology, Merz Investigational Site #0440047; 🇬🇧 Exeter, United Kingdom

The Walton Centre NHS Foundation Trust; Neuroscience Research Centre; Merz Investigational site #0440004; 🇬🇧 Liverpool, United Kingdom

National Hospital for Neurology and Neurosurgery - UCLH; Merz Investigational Site #0440033; 🇬🇧 London, United Kingdom