Lower Limb or Combined Lower Limb and Upper Limb Spasticity Due to Stroke or Traumatic Brain Injury Clinical Trial
— PATTERNOfficial 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
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.
| Status | Recruiting |
| Enrollment | 600 |
| Est. completion date | April 2027 |
| Est. primary completion date | August 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 85 Years |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | 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 | |
| Belgium | 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 | |
| Czechia | 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 | |
| France | 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 | |
| Germany | Uniklinik RWTH Aachen, Neurologie, Merz Investigational Site #0490191 | Aachen | |
| Germany | Neurologie Bewegt; Merz Investigational site #0490378 | Berlin | |
| 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 | |
| Hungary | Petz Hospital, Neurology, Merz Investigational Site #0360010 | Gyor | |
| Hungary | St.Damjan Hospital, Kisvarda; Merz investigational site #0360019 | Kisvárda | |
| Hungary | University of Szeged, Department of Neurology, Merz investigational site #0360008 | Szeged | |
| Italy | 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 | |
| Norway | Haukeland University Hospital, Dept of Neurology; Merz investigational site #0470001 | Bergen | |
| Norway | Sunnaas Rehabilitation Hospital, Merz Investigational Site #0470002 | Bjornemyr | |
| Poland | Specjalistyczna Praktyka Lekarska Dr. n. med Stanislaw Ochudlo, 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 | Instytut Psychiatrii i Neurologii, II Klinika Neurologiczna, Merz Investigational Site #0480023 | Warsaw | |
| Poland | Mazowiecki Szpital Brodnowski, Merz investigational site #0480064 | Warsaw | |
| Poland | Projekt Samodzielni Sp z o.o., Merz Investigational Site #0480099 | Warsaw | |
| Poland | Neuryt Diagnostyka I Terapia Neurologiczna, Merz investigational site #0480106 | Wroclaw | |
| Russian Federation | 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 | 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 | 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 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 | |
| Slovakia | University Hospital Bratislav, 2nd Dept. of Neurology, Merz Investigational Site # 4210005 | Bratislava | |
| Slovakia | Neurologicka klinika, Fakultna nemocnica Trnava; Merz investigational site #4210009 | Trnava | |
| Spain | 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 | |
| Switzerland | 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 | |
| Ukraine | 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 | |
| United Kingdom | 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 States | Nova Clinical Research, Merz investigational site #0010474 | Bradenton | Florida |
| United States | Howard A. Rusk Rehabilitation Center; Merz investigational site #0010283 | Columbia | Missouri |
| United States | UT Southwestern Medical Center, Department of Physical Medicine & Rehabilitation, Merz investigational site #0010082 | Dallas | Texas |
| United States | Rancho Research Institute at Rancho Los Amigos National Rehabilitation Center; Merz investigational site #0010184 | Downey | California |
| United States | Neurology Center of New England P.C., Merz investigative site #0010476 | Foxboro | Massachusetts |
| 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 | 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 | New England institute for clinical research; Merz Investigational Site #0010441 | Stamford | Connecticut |
| United States | Rehabilitation Hospital, Kessler Institute for Rehabilitation, Merz Investigational Site #0010199 | West Orange | New Jersey |
| Lead Sponsor | Collaborator |
|---|---|
| Merz Pharmaceuticals GmbH |
United States, Australia, Belgium, Czechia, France, Germany, Hungary, Italy, Norway, Poland, Russian Federation, Slovakia, Spain, Switzerland, Ukraine, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | |
| Primary | 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 | |
| Primary | Occurrence of treatment emergent adverse events [TEAEs] in the Main Period | Baseline to week 12 | ||
| Secondary | Change from Study Baseline in Goal Attainment Scale [GAS] at Week 6 | The GAS is a 6-grade scale | Baseline to week 6 | |
| Secondary | Global Impression of Change Scale (GICS) assessed by the study subject at Week 4 to 6 | The GICS s a 9-grade scale | Week 4-6 | |
| Secondary | Global Impression of Change Scale (GICS) assessed by the caregiver at Week 4 to 6 | The GICS s a 9-grade scale | Week 4-6 |