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 (PATTERN)

April 18, 2024 updated by: Merz Pharmaceuticals GmbH

Prospective, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Investigate the Efficacy and Safety of NT 201 in the Treatment of Lower Limb Spasticity Caused by Stroke or Traumatic Brain Injury in Adult Subjects, Followed by an Open Label Extension With or Without Combined Upper Limb Treatment

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

600

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
      • Kogarah, Australia, 2217
        • Withdrawn
        • St George Hospital, Department of Rehabilitation Medicine, Merz Investigational Site #0610004
      • Parkville, Australia, 3052
        • Withdrawn
        • Royal Melbourne Hospital, Department of Rehabilitation Medicine; Merz Investigational Site #0610002
  • Belgium
      • Brussel, Belgium, 1020
        • Recruiting
        • CHU Brugmann Neurology; Merz investigational site #0320015
      • Bruxelles, Belgium, 1200
        • Recruiting
        • UCL Bruxelles, Physical Medicine & Rehabilitation Department, Merz Investigational Site #0320013
      • Pellenberg, Belgium, 3212
        • Recruiting
        • UZ Leuven Pellenberg campus; Merz investigational site #0320014
      • Yvoir, Belgium, 5530
        • Recruiting
        • UCL Mont Godinne, Physical Medicine & Rehabilitation Department; Merz Investigational Site #0320008
  • Czechia
      • Brno, Czechia, 61500
        • Recruiting
        • Neurology and Physiotherapy Skopalikova, Merz Investigational Site #4200049
      • Ostrava, Czechia, 708 52
        • Recruiting
        • University Hospital Ostrava; Neurology Departement, Merz investigational site #4200024
      • Pardubice, Czechia, 530 03
        • Recruiting
        • Pardubice Regional Hospital; Merz investigational site #4200025
      • Prague, Czechia, 10034
        • Withdrawn
        • Fakultni nemocnice Kralovske Vinohrady, Neurology Department, Merz Investigational Site #4200050
  • France
      • Garches, France, 92380
        • Recruiting
        • Raymond Poincaré University Hospital, Service de MPR Pôle Handicap-Rééducation, Merz Investigational site #00330018
      • Lille, France, 59000
        • Recruiting
        • CHU Lille/Hôpital Swynghedauw; investigational site # 0330045
      • Rennes, France, 35000
        • Recruiting
        • Pôle Saint-Hélier; Merz investigational site #0330024
      • Strasbourg, France, 67000
        • Recruiting
        • Institut Universitaire de Readaptation Clemenceau, Physical Medicine / Rehabilitation Medecine, Merz Investigational site # 0330063
      • Toulouse, France, 31059
        • Recruiting
        • Rangueil Hospital-University Hospital Center (CHU) of Toulouse, Médecine physique et de réadaptation, Merz investigational site #0330025
  • Germany
      • Aachen, Germany, 52074
        • Recruiting
        • Uniklinik RWTH Aachen, Neurologie, Merz Investigational Site #0490191
      • Berlin, Germany, 10627
        • Active, not recruiting
        • Neurologie Bewegt; Merz Investigational site #0490378
      • Düsseldorf, Germany, 40225
        • Recruiting
        • Heinrich Heine University Duesseldorf, Department of Neurology; Merz Investigational Site #0490071
      • Hamburg, Germany, 20246
        • Recruiting
        • Universitätsklinikum Hamburg-Eppendorf, Merz Investigational site #0490079
      • Lübeck, Germany, 23562
        • Withdrawn
        • CBBM, Institut für Neurogenetik, Haus 66; Merz Investigational Site #0490332
      • Wiesbaden, Germany, 65191
        • Recruiting
        • DKD HELIOS Medical Center, Fachbereich Neurologie, Merz Investigational Site #0490081
      • Würzburg, Germany, 97080
        • Recruiting
        • Neurologische Klinik und Poliklinik des Universitätsklinikums Würzburg, Merz Investigational Site #0490302
  • Hungary
      • Győr, Hungary, 9024
        • Recruiting
        • Petz Hospital, Neurology, Merz Investigational Site #0360010
      • Kisvárda, Hungary, 4600
        • Recruiting
        • St.Damjan Hospital, Kisvarda; Merz investigational site #0360019
      • Szeged, Hungary, 6725
        • Recruiting
        • University of Szeged, Department of Neurology, Merz investigational site #0360008
  • Italy
      • Costa Masnaga, Italy, 23845
        • Withdrawn
        • Ospedale Valduce, Villa Beretta Rehabilitation Center, Merz investigational site #0390005
      • Foggia, Italy, 71122
        • Recruiting
        • Azienda Ospedaliera Universitaria Ospedali Riuniti Di Foggia; Merz Investigational Site #0390018
      • Genova, Italy, 16132
        • Recruiting
        • IRCCS Ospedale Policlinico S. Martino, U.O.Complessa Riabilitazione e Rieducazione Funzionale; Merz investigational site #0390020
      • Novara, Italy, 28100
        • Recruiting
        • Ospedale Maggiore della Carita, Dipartimento di Medicina fisica e Riabilitativa, Merz Investigational Site #0390017
      • Terracina, Italy, 04019
        • Recruiting
        • Ospedale Alfredo Fiorini, UOSD Neurologia Universitaria; Merz Investigational site #0390022
      • Verona, Italy, 37134
        • Recruiting
        • AOUI -Ospedale Borgo Roma, U.O.C Neuroriabilitazione, Merz Investigational Site #0390014
  • Norway
      • Bergen, Norway, 5053
        • Withdrawn
        • Haukeland University Hospital, Dept of Neurology; Merz investigational site #0470001
      • Bjornemyr, Norway, 1453
        • Withdrawn
        • Sunnaas Rehabilitation Hospital, Merz Investigational Site #0470002
  • Poland
      • Katowice, Poland, 40-097
        • Recruiting
        • Specjalistyczna Praktyka Lekarska Dr. n. med Stanisław Ochudło, Merz Investigational Site #0480077
      • Krakow, Poland, 30-539
        • Recruiting
        • Specjalistyczne Gabinety Sp z o.o., Merz Investigational Site #0480059
      • Lodz, Poland, 90-640
        • Recruiting
        • NeuroKlinika Gabinet Lekarski Prof Andrzej Bogucki, Merz Investigational Site #0480101
      • Lublin, Poland, 20-582
        • Recruiting
        • Indywidualna Praktyka Lekarska dr. hab. Med. Anna Szczepanska-Szerej, Merz Investigational Site #0480096
      • Warsaw, Poland, 01-518
        • Recruiting
        • Filia 7 Centrum Kompleksowej Rehabilitacji Sp. z o.o., Merz Investigational Site #0480100
      • Warsaw, Poland, 02-042
        • Recruiting
        • Projekt Samodzielni Sp z o.o., Merz Investigational Site #0480099
      • Warsaw, Poland, 02-957
        • Recruiting
        • Instytut Psychiatrii i Neurologii, II Klinika Neurologiczna, Merz Investigational Site #0480023
      • Warsaw, Poland, 03-242
        • Completed
        • Mazowiecki Szpital Bródnowski, Merz Investigational Site #0480064
      • Wroclaw, Poland, 50-305
        • Recruiting
        • Neuryt Diagnostyka I Terapia Neurologiczna, Merz investigational site #0480106
  • Russian Federation
      • Krasnoyarsk, Russian Federation, 660049
        • Completed
        • 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
      • Moscow, Russian Federation, 105005
        • Completed
        • 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, 125367
        • Completed
        • 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
      • Saint Petersburg, Russian Federation, 195119
        • Completed
        • 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
  • Slovakia
      • Bratislava, Slovakia, 83305
        • Recruiting
        • University Hospital Bratislav, 2nd Dept. of Neurology, Merz Investigational Site # 4210005
      • Trnava, Slovakia, 917 01
        • Recruiting
        • Neurologicka klinika, Fakultna nemocnica Trnava; Merz investigational site #4210009
  • Spain
      • Huelva, Spain, 21005
        • Recruiting
        • Hospital Universitario Juan Ramón Jiménez, Merz Investigational Site #0340037
      • Madrid, Spain, 28046
        • Recruiting
        • Hospital Universitario La Paz, Merz Investigational Site #0340007
      • Terrassa, Spain, 08221
        • Recruiting
        • Hospital Universitari Mútua de Terrassa, Merz Investigational Site #0340003
  • Switzerland
      • Bern, Switzerland, 3010
        • Recruiting
        • University Hospital of Bern, Center of Parkinson's diseases and Movement disorders (ZfPB), Merz investigational site #0410015
      • Lausanne, Switzerland, 1011
        • Recruiting
        • Centre Hospitalier Universitaire Vaudois - Neurorehabilitation and Physical Medicine, Merz Investigational Site #0410013
      • Meyriez, Switzerland, 3280
        • Recruiting
        • HFR Fribourg - Hôpital Cantonal, Department of Rehabilitation, Merz Investigational site #0410014
  • Ukraine
      • Kharkiv, Ukraine, 61000
        • Recruiting
        • Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine, MC "Neuron", Merz Investigational Site #3800018
      • Kharkiv, Ukraine, 61000
        • Recruiting
        • Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine; Merz Investigational Site #3800019
      • Lviv, Ukraine, 79010
        • Recruiting
        • Lviv regional clinical hospital; Merz investigational site # 3800020
      • Rivne, Ukraine, 33001
        • Recruiting
        • Rivne City Hospital 2, Department of Clinical Neurology and Neurorehabilitation; Merz investigational site #3800016
      • Uzhgorod, Ukraine, 88018
        • Recruiting
        • NPE "Regional Clinical Centre of Neurosurgery and Neurology" Transcarpathian Regional Council; Merz investigational site #3800014
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
        • Recruiting
        • Cambridge University Hospitals NHS Foundation Trust; Merz Investigational Site 0440023
      • Exeter, United Kingdom, EX2 5DW
        • Recruiting
        • Royal Devon and Exeter Foundation Trust Hospital, Department of Neurology, Merz Investigational Site #0440047
      • Liverpool, United Kingdom, L9 7LJ
        • Recruiting
        • The Walton Centre NHS Foundation Trust; Neuroscience Research Centre; Merz Investigational site #0440004
      • London, United Kingdom, WC1N 3BG
        • Withdrawn
        • National Hospital for Neurology and Neurosurgery - UCLH; Merz Investigational Site #0440033
  • United States
    • California
      • Downey, California, United States, 90242
        • Recruiting
        • Rancho Research Institute at Rancho Los Amigos National Rehabilitation Center; Merz investigational site #0010184
    • Connecticut
      • Stamford, Connecticut, United States, 06905
        • Recruiting
        • New England institute for clinical research; Merz Investigational Site #0010441
    • Florida
      • Bradenton, Florida, United States, 34209
        • Recruiting
        • Nova Clinical Research, Merz investigational site #0010474
    • Missouri
      • Columbia, Missouri, United States, 65203
        • Recruiting
        • Howard A. Rusk Rehabilitation Center; Merz investigational site #0010283
    • New Jersey
      • West Orange, New Jersey, United States, 07052
        • Withdrawn
        • Rehabilitation Hospital, Kessler Institute for Rehabilitation, Merz Investigational Site #0010199
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Weill Cornell Medical Center, Department of Rehabilitation Medicine; Merz Investigational Site #0010440
      • New York, New York, United States, 10029
        • Active, not recruiting
        • Icahn School of Medicine at Mount Sinai, Neurology Department, Merz Investigational Site #0010191
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • University of Pittsburgh Medical Center, Physical Medicine & Rehabiliation, Merz Investigational Site #0010211
    • Texas
      • Dallas, Texas, United States, 75390-9055
        • Recruiting
        • UT Southwestern Medical Center, Department of Physical Medicine & Rehabilitation, Merz investigational site #0010082
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas Health Science Center McGovern, Medical School Department of PM&R; merz investigational site #0010183
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin,Department of PM&R, Merz Investigational Site #0010237

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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).
Other Names:
  • Xeomin
  • Botulinum toxin type A (150 kiloDalton), free from complexing proteins
  • IncobotulinumtoxinA
  • Incobotulinumtoxin A
Placebo Comparator: 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.
Drug: Placebo
Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).
Drug: 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).
Other Names:
  • Xeomin
  • Botulinum toxin type A (150 kiloDalton), free from complexing proteins
  • IncobotulinumtoxinA
  • Incobotulinumtoxin A

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in derived Modified Ashworth Scale-Bohannon (MAS) ankle score (knee extended) at weeks 4 to 6
Time Frame: Baseline to week 4-6
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
Time Frame: Week 4-6
The GICS s a 9-grade scale
Week 4-6
Occurrence of treatment emergent adverse events [TEAEs] in the Main Period
Time Frame: Baseline to week 12
Baseline to week 12

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merz Pharmaceuticals GmbH

Investigators

  • Study Director: Merz Medical Expert, Merz Pharmaceuticals GmbH

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 16, 2019

Primary Completion (Estimated)

August 1, 2025

Study Completion (Estimated)

April 1, 2027

Study Registration Dates

First Submitted

June 18, 2019

First Submitted That Met QC Criteria

June 18, 2019

First Posted (Actual)

June 20, 2019

Study Record Updates

Last Update Posted (Actual)

April 19, 2024

Last Update Submitted That Met QC Criteria

April 18, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M602011014
  • 2018-001639-35 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Myanmar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe