Clinical trial NCT03992404: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Lower Limb or Combined Lower Limb and Upper Limb Spasticity Due to Stroke or Traumatic Brain Injury
Lead sponsor: Merz Pharmaceuticals GmbH
Sponsor class: INDUSTRY
First posted: 2019-06-20
Enrollment: 603
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in derived Modified Ashworth Scale-Bohannon (MAS) ankle score (knee extended) at weeks 4 to 6
timeFrame: Baseline to week 4-6
measure: Co-Primary: Global Impression of Change Scale (GICS) assessed by physician at Week 4 to 6
timeFrame: Week 4-6
measure: Occurrence of treatment emergent adverse events [TEAEs] in the Main Period
timeFrame: Baseline to week 12
Secondary outcomes:
measure: Change from Study Baseline in Goal Attainment Scale [GAS] at Week 6
timeFrame: Baseline to week 6
measure: Global Impression of Change Scale (GICS) assessed by the study subject at Week 4 to 6
timeFrame: Week 4-6
measure: Global Impression of Change Scale (GICS) assessed by the caregiver at Week 4 to 6
timeFrame: Week 4-6
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Physical Medicine and Rehabilitation at University of Alabama at Birmingham; Merz investigational site #0010479
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences, Merz investigational site #0010481
state: Arkansas
city: Downey
country: United States
facility: Rancho Research Institute at Rancho Los Amigos National Rehabilitation Center; Merz investigational site #0010184
state: California
city: Stamford
country: United States
facility: New England institute for clinical research; Merz Investigational Site #0010441
state: Connecticut
city: Bradenton
country: United States
facility: Nova Clinical Research, Merz investigational site #0010474
state: Florida
city: Jacksonville
country: United States
facility: Brooks Rehabilitation Clinical Integration and Research, Merz investigational site #0010483
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Health Care System, Rehabilitation Medicine, Merz investigational site #0010478
state: Florida
city: Foxboro
country: United States
facility: Neurology Center of New England P.C., Merz investigative site #0010476
state: Massachusetts
city: Columbia
country: United States
facility: Howard A. Rusk Rehabilitation Center; Merz investigational site #0010283
state: Missouri
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai, Neurology Department, Merz Investigational Site #0010191
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center, Department of Rehabilitation Medicine; Merz Investigational Site #0010440
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center, Physical Medicine & Rehabiliation, Merz Investigational Site #0010211
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center, Department of Physical Medicine & Rehabilitation, Merz investigational site #0010082
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center McGovern, Medical School Department of PM&R; merz investigational site #0010183
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin,Department of PM&R, Merz Investigational Site #0010237
state: Wisconsin
city: Brussel
country: Belgium
facility: CHU Brugmann Neurology; Merz investigational site #0320015
city: Bruxelles
country: Belgium
facility: UCL Bruxelles, Physical Medicine & Rehabilitation Department, Merz Investigational Site #0320013
city: Pellenberg
country: Belgium
facility: UZ Leuven Pellenberg campus; Merz investigational site #0320014
city: Yvoir
country: Belgium
facility: UCL Mont Godinne, Physical Medicine & Rehabilitation Department; Merz Investigational Site #0320008
city: Edmonton
country: Canada
facility: Glenrose Rehabilitation Hospital, Merz investigational site #0010195
city: Brno
country: Czechia
facility: Neurology and Physiotherapy Skopalikova, Merz Investigational Site #4200049
city: Ostrava
country: Czechia
facility: University Hospital Ostrava; Neurology Departement, Merz investigational site #4200024
city: Pardubice
country: Czechia
facility: Pardubice Regional Hospital; Merz investigational site #4200025
city: Garches
country: France
facility: Raymond Poincaré University Hospital, Service de MPR Pôle Handicap-Rééducation, Merz Investigational site #00330018
city: Lille
country: France
facility: CHU Lille/Hôpital Swynghedauw; investigational site # 0330045
city: Rennes
country: France
facility: Pôle Saint-Hélier; Merz investigational site #0330024
city: Strasbourg
country: France
facility: Institut Universitaire de Readaptation Clemenceau, Physical Medicine / Rehabilitation Medecine, Merz Investigational site # 0330063
city: Toulouse
country: France
facility: Rangueil Hospital-University Hospital Center (CHU) of Toulouse, Médecine physique et de réadaptation, Merz investigational site #0330025
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen, Neurologie, Merz Investigational Site #0490191
city: Berlin
country: Germany
facility: Neurologie Bewegt; Merz Investigational site #0490378
city: Bonn
country: Germany
facility: University of Bonn Medical Center, Department of Neurodegenerative disease, Merz investigational site #0490390
city: Düsseldorf
country: Germany
facility: Heinrich Heine University Duesseldorf, Department of Neurology; Merz Investigational Site #0490071
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, Merz Investigational site #0490079
city: Wiesbaden
country: Germany
facility: DKD HELIOS Medical Center, Fachbereich Neurologie, Merz Investigational Site #0490081
city: Würzburg
country: Germany
facility: Neurologische Klinik und Poliklinik des Universitätsklinikums Würzburg, Merz Investigational Site #0490302
city: Győr
country: Hungary
facility: Petz Hospital, Neurology, Merz Investigational Site #0360010
city: Kisvárda
country: Hungary
facility: St.Damjan Hospital, Kisvarda; Merz investigational site #0360019
city: Szeged
country: Hungary
facility: University of Szeged, Department of Neurology, Merz investigational site #0360008
city: Foggia
country: Italy
facility: Azienda Ospedaliera Universitaria Ospedali Riuniti Di Foggia; Merz Investigational Site #0390018
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico S. Martino, U.O.Complessa Riabilitazione e Rieducazione Funzionale; Merz investigational site #0390020
city: Novara
country: Italy
facility: Ospedale Maggiore della Carita, Dipartimento di Medicina fisica e Riabilitativa, Merz Investigational Site #0390017
city: Terracina
country: Italy
facility: Ospedale Alfredo Fiorini, UOSD Neurologia Universitaria; Merz Investigational site #0390022
city: Katowice
country: Poland
facility: Specjalistyczna Praktyka Lekarska Dr. n. med Stanisław Ochudło, Merz Investigational Site #0480077
city: Krakow
country: Poland
facility: Specjalistyczne Gabinety Sp z o.o., Merz Investigational Site #0480059
city: Lodz
country: Poland
facility: NeuroKlinika Gabinet Lekarski Prof Andrzej Bogucki, Merz Investigational Site #0480101
city: Lublin
country: Poland
facility: Indywidualna Praktyka Lekarska dr. hab. Med. Anna Szczepanska-Szerej, Merz Investigational Site #0480096
city: Warsaw
country: Poland
facility: Filia 7 Centrum Kompleksowej Rehabilitacji Sp. z o.o., Merz Investigational Site #0480100
city: Warsaw
country: Poland
facility: Projekt Samodzielni Sp z o.o., Merz Investigational Site #0480099
city: Warsaw
country: Poland
facility: Instytut Psychiatrii i Neurologii, II Klinika Neurologiczna, Merz Investigational Site #0480023
city: Warsaw
country: Poland
facility: Mazowiecki Szpital Brodnowski, Merz investigational site #0480064
city: Wroclaw
country: Poland
facility: Neuryt Diagnostyka I Terapia Neurologiczna, Merz investigational site #0480106
city: Krasnoyarsk
country: Russian Federation
facility: 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
city: Moscow
country: Russian Federation
facility: 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
city: Moscow
country: Russian Federation
facility: 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
city: Saint Petersburg
country: Russian Federation
facility: 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
city: Bratislava
country: Slovakia
facility: University Hospital Bratislav, 2nd Dept. of Neurology, Merz Investigational Site # 4210005
city: Trnava
country: Slovakia
facility: Neurologicka klinika, Fakultna nemocnica Trnava; Merz investigational site #4210009
city: Huelva
country: Spain
facility: Hospital Universitario Juan Ramón Jiménez, Merz Investigational Site #0340037
city: Madrid
country: Spain
facility: Hospital Universitario La Paz, Merz Investigational Site #0340007
city: Terrassa
country: Spain
facility: Hospital Universitari Mútua de Terrassa, Merz Investigational Site #0340003
city: Bern
country: Switzerland
facility: University Hospital of Bern, Center of Parkinson's diseases and Movement disorders (ZfPB), Merz investigational site #0410015
city: Meyriez
country: Switzerland
facility: HFR Fribourg - Hôpital Cantonal, Department of Rehabilitation, Merz Investigational site #0410014
city: Sion
country: Switzerland
facility: CRR, Mee Suva (Clinique romande de réadaptation), Merz investigational site #0410016
city: Kharkiv
country: Ukraine
facility: Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine, MC "Neuron", Merz Investigational Site #3800018
city: Kharkiv
country: Ukraine
facility: Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine; Merz Investigational Site #3800019
city: Lviv
country: Ukraine
facility: Lviv regional clinical hospital; Merz investigational site # 3800020
city: Rivne
country: Ukraine
facility: Rivne City Hospital 2, Department of Clinical Neurology and Neurorehabilitation; Merz investigational site #3800016
city: Uzhgorod
country: Ukraine
facility: NPE "Regional Clinical Centre of Neurosurgery and Neurology" Transcarpathian Regional Council; Merz investigational site #3800014
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust; Merz Investigational Site 0440023
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Foundation Trust Hospital, Department of Neurology, Merz Investigational Site #0440047
city: Liverpool
country: United Kingdom
facility: The Walton Centre NHS Foundation Trust; Neuroscience Research Centre; Merz Investigational site #0440004
Study officials:
affiliation: Merz Pharmaceuticals GmbH
name: Merz Medical Expert
role: STUDY_DIRECTOR
References: