Clinical trial • Phase III • Neurology

CLOSTRIDIUM BOTULINUM NEUROTOXIN TYPE A (150KD), FREE OF COMPLEXING PROTEINS for Lower limb spasticity|Post-stroke spasticity|Traumatic brain injury-related spasticity

Phase III trial of CLOSTRIDIUM BOTULINUM NEUROTOXIN TYPE A (150KD), FREE OF COMPLEXING PROTEINS for Lower limb spasticity|Post-stroke spasticity|Traumatic…

Overview

Trial Therapeutic Area
Neurology
Trial Disease
Lower limb spasticity|Post-stroke spasticity|Traumatic brain injury-related spasticity
Trial Stage
Phase III
Drug Modality
Peptide/protein/enzyme

Key dates

Initial CTIS Submission Date
05-07-2024
First CTIS Authorization Date
02-08-2024

Trial design

Randomised, open-label, placebo to nt 201 — intramuscular placebo injection (matched appearance) used as comparator; active arm: xeomin (nt 201) 400 units intramuscular (main period, single treatment cycle).-controlled Phase III trial across 34 sites in Belgium, Czechia, France and others.

Randomised
Yes
Open Label
Yes
Comparator
Placebo to NT 201 — intramuscular placebo injection (matched appearance) used as comparator; active arm: Xeomin (NT 201) 400 Units intramuscular (Main Period, single treatment cycle).
Target Sample Size
257
Trial Duration For Participant
92

Eligibility

Recruits 257 Vulnerable population selected (isVulnerablePopulationSelected=true). Caregiver information and caregiver informed consent forms are provided (caregiver ICF documents listed) in addition to subject ICFs..

Pregnancy Exclusion
Pregnancy (as verified by a positive pregnancy test) or breast feeding.
Vulnerable Population
Vulnerable population selected (isVulnerablePopulationSelected=true). Caregiver information and caregiver informed consent forms are provided (caregiver ICF documents listed) in addition to subject ICFs.

Inclusion criteria

  • {"criterion_text":"- Female or male subject ≥ 18 years and ≤ 85 years at screening\n- Diagnosis of lower limb spasticity with or without upper limb spasticity of the same body side caused by stroke or traumatic brain injury\n- Disabling ankle flexor spasticity presenting as pes equinus or pes equinovarus\n- 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)\n- Minimum passive range of motion in ankle of the target lower limb (supine position, knee extended): 10°dorsiflexion and 20°plantarflexion\n- At least 4 months since last botulinum neurotoxin [BoNT] injection for treatment of spasticity or any other condition\n- For subjects receiving anticoagulation therapy, the investigator confirms and documents that the subject has an: o Activated partial thromboplastin time [aPTT] ≤ 80 seconds (subjects on dabigatran or other direct thrombin inhibitors) or o International normalized ratio [INR] value of ≤ 2.5 (subjects on coumarins or other anticoagulants monitored by INR)."}

Exclusion criteria

  • {"criterion_text":"- 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\n- Bilateral lower limb paresis/paralysis/spasticity or tetraparesis/paralysis/spasticity\n- Body weight < 50 kg\n- Severe atrophy of the target limb muscles\n- Previous, ongoing or planned treatments of spasticity with intrathecal baclofen\n- Previous, ongoing, or planned treatments of spasticity in the target lower limb with any of the following procedures: o Surgical intervention o Alcohol or phenol block o Muscle afferent block\n- 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\n- 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\n- Infection or inflammation at the injection sites\n- Subjects with presence or history of aspiration pneumonia, recurrent lower respiratory tract infections, or compromised respiratory function as per investigator's clinical judgment\n- Pregnancy (as verified by a positive pregnancy test) or breast feeding."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Change from baseline in derived MAS ankle score (knee extended) at Weeks 4 to 6 (using a value modelled from the actual values measured at Week 4 [V3] and Week 6 [V4])","definition_or_measurement_approach":"Change from baseline in derived Modified Ashworth Scale (MAS) ankle score (knee extended) at Weeks 4–6; value modelled from actual values measured at Week 4 (V3) and Week 6 (V4)."}
  • {"endpoint_text":"- GICS assessed by physician at Week 4 to 6 (using a value modelled from the actual values measured at Week 4 [V3] and Week 6 [V4]) (co-primary for US regulatory authority only, otherwise secondary).","definition_or_measurement_approach":"Global Impression of Change Scale (GICS) assessed by the physician at Weeks 4–6; using a value modelled from the actual values measured at Week 4 (V3) and Week 6 (V4). (Co-primary for US regulatory authority only.)"}
  • {"endpoint_text":"- Primary safety variable: • Occurrence of treatment emergent adverse events [TEAEs] in Main Period.","definition_or_measurement_approach":"Safety assessed by occurrence and recording of treatment-emergent adverse events (TEAEs) during the Main Period."}

Secondary endpoints

  • {"endpoint_text":"- Key secondary efficacy variable: Change from Study Baseline in Goal Attainment Scale [GAS] at Week 6 (V4)","definition_or_measurement_approach":"Change from study baseline on the Goal Attainment Scale (GAS) at Week 6 (V4)."}
  • {"endpoint_text":"- GICS assessed by subject at Week 4 (V3) to Week 6 (V4)","definition_or_measurement_approach":"Subject-reported Global Impression of Change Scale (GICS) assessed between Week 4 (V3) and Week 6 (V4)."}
  • {"endpoint_text":"- GICS assessed by caregiver at Week 4 (V3) to Week 6 (V4).","definition_or_measurement_approach":"Caregiver-reported Global Impression of Change Scale (GICS) assessed between Week 4 (V3) and Week 6 (V4)."}

Recruitment

Planned Sample Size
257
Recruitment Window Months
88
Consent Approach
Informed consent is obtained from subjects (subjects are adults ≥18 years). Caregiver informed consent forms are provided where applicable (caregiver ICF documents listed). Subject ICF and caregiver ICF/patient information sheets are available in multiple languages (documents provided in French, Dutch/Flemish, German, Italian, Spanish, Polish, Czech, Hungarian, Slovak and English).

Geography

Total Number Of Sites
34
Total Number Of Participants
343

Belgium

Latest Decision Or Authorization Date
02-08-2024
Number Of Sites
2
Number Of Participants
12

Sites

Site Name
Chu Brugmann
Department Name
Neurology
Contact Person Name
Gérald Glibert
Contact Person Email
Gerald.Glibert@chu-brugmann.be
Site Name
Centre Hospitalier Universitaire Dinant Godinne Sainte-Elisabeth-UCL-Namur
Department Name
Physical medicine and rehabilitation department
Contact Person Name
Thierry Deltombe
Contact Person Email
thierry.deltombe@uclouvain.be

Czechia

Latest Decision Or Authorization Date
06-08-2024
Number Of Sites
3
Number Of Participants
60

Sites

Site Name
Fakultni Nemocnice Ostrava
Department Name
Neurology
Contact Person Name
Ivana Woznicová
Contact Person Email
ivana.woznicova@fno.cz
Site Name
Neurologie a rehabilitace Skopalikova
Department Name
Neurology
Contact Person Name
Eduard Minks
Contact Person Email
eduardminks@seznam.cz
Site Name
Nemocnice Pardubickeho kraje a.s.
Department Name
Neurology
Contact Person Name
Edvard Ehler
Contact Person Email
edvard.ehler@nempk.cz

France

Latest Decision Or Authorization Date
02-08-2024
Number Of Sites
5
Number Of Participants
10

Sites

Site Name
Raymond-Poincare Hospital
Department Name
Service de MPR Pôle Handicap-Rééducation
Contact Person Name
Djamel Bensmail
Contact Person Email
djamel.bensmail@aphp.fr
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Service de MPR
Contact Person Name
Marie-Eve Isner-Horobeti
Contact Person Email
marieeve.isner@gmail.com
Site Name
Saint Helier
Department Name
Service de MPR
Contact Person Name
Philippe Gallien
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Service de MPR
Contact Person Name
Etienne Allart
Contact Person Email
etienne.allart@chu-lille.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Médecine physique et de réadaptation Pôle neurosciences
Contact Person Name
Philippe Marque
Contact Person Email
marque.ph@chu-toulouse.fr

Germany

Latest Decision Or Authorization Date
02-08-2024
Number Of Sites
6
Number Of Participants
38

Sites

Site Name
Universitaetsklinikum Wuerzburg AöR
Department Name
Neurologische Klinik und Poliklinik des Universitätsklinikums Würzburg, Kopfkliniken
Contact Person Name
Chi Wang Ip
Contact Person Email
ip_c@ukw.de
Site Name
DKD HELIOS Klinik Wiesbaden GmbH
Department Name
Fachbereich Neurologie
Contact Person Name
Wolfgang Fogel
Site Name
Universitaetsklinikum Duesseldorf AöR
Department Name
Klinik für Neurologie
Contact Person Name
Philipp Albrecht
Contact Person Email
phil.albrecht@gmail.com
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum
Contact Person Name
Mathias Gelderblom
Contact Person Email
m.gelderblom@uke.de
Site Name
Universitaetsklinikum Bonn AöR
Department Name
Klinik für Neurodegenerative Erkrankungen und Gerontopsychiatrie
Contact Person Name
Pawel Tacik
Contact Person Email
pawel.tacik@ukbonn.de
Site Name
Universitaetsklinikum Aachen AöR
Department Name
Klinik für Neurologie
Contact Person Name
Manuel Dafotakis
Contact Person Email
mdafotakis@ukaachen.de

Hungary

Latest Decision Or Authorization Date
02-08-2024
Number Of Sites
3
Number Of Participants
12

Sites

Site Name
Szent Damjan Goeroegkatolikus Korhaz
Department Name
Neurológiai és Stroke Osztály
Contact Person Name
Marina Czurko
Contact Person Email
dr.czurkomarina@gmail.com
Site Name
University Of Szeged
Department Name
Department of Neurology
Contact Person Name
Peter Klivenyi
Contact Person Email
klivenyi.peter@med.u-szeged.hu
Site Name
Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktato Korhaz
Department Name
Neurológiai Osztály és Stroke Részleg
Contact Person Name
Attila Csanyi
Contact Person Email
csanyia@petz.gyor.hu

Italy

Latest Decision Or Authorization Date
07-08-2024
Number Of Sites
3
Number Of Participants
16

Sites

Site Name
Azienda Ospedaliero-Universitaria Maggiore Della Carita
Department Name
Dipartimento di Medicina fisica e Riabilitativa
Contact Person Name
Marco Battaglia
Contact Person Email
marco.battaglia@unipo.it
Site Name
Azienda Ospedaliero Universitaria Ospedali Riuniti
Department Name
Dipartimento Assistenzionale Integrato (DAI) di Neuriscienze
Contact Person Name
Andrea Santamato
Contact Person Email
andrea.santamato@unifg.it
Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
U.O.Complessa Riabilitazione e Rieducazione Funzionale
Contact Person Name
Carlo Trompetto
Contact Person Email
ctrompetto@neurologia.unige.it

Spain

Latest Decision Or Authorization Date
05-08-2024
Number Of Sites
3
Number Of Participants
22

Sites

Site Name
Hospital Universitario La Paz
Department Name
Neurology
Contact Person Name
Eishe Abdel-Muti Garcia
Contact Person Email
eishe.abdel@salud.madrid.org
Site Name
Hospital Universitario Juan Ramon Jimenez
Department Name
neurology
Contact Person Name
Carlos Cordero
Contact Person Email
ccordero.rhb@gmail.com
Site Name
Fundacio Assistencial De Mutua De Terrassa Fpc
Department Name
Neurology
Contact Person Name
Jerzy Krupinski
Contact Person Email
jkrupinski@mutuaterrassa.es

Poland

Latest Decision Or Authorization Date
29-08-2024
Number Of Sites
7
Number Of Participants
155

Sites

Site Name
Neuryt Diagnostyka I Terapia Neurologiczna
Contact Person Name
Katarzyna Mariańska
Contact Person Email
marianska.katarzyna@gmail.com
Site Name
Project Samodzielni Sp.z.o.o
Contact Person Name
Anna Potulska-Chromik
Contact Person Email
orsonok@gmail.com
Site Name
NeuroKlinika Gabinet Lekarski Prof. Andrzej Bogucki
Contact Person Name
Andrzej Bogucki
Contact Person Email
andrzej.bogucki@umed.lodz.pl
Site Name
Instytut Psychiatrii I Neurologii
Department Name
II Klinika Neurologiczna
Contact Person Name
Iwona Kurkowska-Jastrzębska
Contact Person Email
ikurkowska@ipin.edu.pl
Site Name
Indywidualna Praktyka lekarska Dr. hab. n. med. Anna Szczepańska-Szerej
Contact Person Name
Anna Szczepanska-Szerej
Contact Person Email
aszerej@poczta.onet.pl
Site Name
Specjalistyczne Gabinety Sp. z o.o.
Contact Person Name
Lucyna Horodecka-Wardęga
Site Name
Centrum Kompleksowej Rehabilitacji Sp. z o.o.
Department Name
Filia 7
Contact Person Name
Jacek Bojakowski
Contact Person Email
jaboj@wp.pl

Slovakia

Latest Decision Or Authorization Date
05-08-2024
Number Of Sites
2
Number Of Participants
18

Sites

Site Name
Fakultna Nemocnica Trnava
Department Name
Neurology
Contact Person Name
Georgi Krastev
Contact Person Email
krastevg1@gmail.com
Site Name
University Hospital Bratislava
Department Name
Neurology
Contact Person Name
Peter Valkovič
Contact Person Email
peter.valkovic@gmail.com

Sponsor

Primary sponsor

Full Name
Merz Pharmaceuticals GmbH
Organisation Type
Pharmaceutical company
Country Of Registered Address
Germany

Contract research organisations

Name
WCT Worldwide Clinical Trials GER GmbH
Responsibilities
codes: 1,12,2,5,8
Name
Metronomia Clinical Research GmbH
Responsibilities
codes: 10,6,7
Name
Almac Clinical Services (Ireland) Limited
Responsibilities
codes: 14
Name
Almac Clinical Technologies LLC
Responsibilities
codes: 3

Third parties

  • {"country":"Germany","full_name":"Toxologics GmbH","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Eurofins BioPharma Product Testing Munich GmbH","duties_or_roles":"codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Germany","full_name":"Metronomia Clinical Research GmbH","duties_or_roles":"codes: 10,6,7","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"WCT Worldwide Clinical Trials GER GmbH","duties_or_roles":"codes: 1,12,2,5,8","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Almac Clinical Services (Ireland) Limited","duties_or_roles":"codes: 14","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Group Limited","duties_or_roles":"codes: 14","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"codes: 3","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Infraserv GmbH & Co. Hoechst KG","duties_or_roles":"codes: 15 (value: 24 hours emergency unblinding service)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Xeomin (NT 201)
Active Substance
CLOSTRIDIUM BOTULINUM NEUROTOXIN TYPE A (150KD), FREE OF COMPLEXING PROTEINS
Modality
Peptide/protein/enzyme
Routes Of Administration
INTRAMUSCULAR INJECTION
Route
Intramuscular injection
Authorisation Status
Marketing authorisations present in multiple member states (product entries show prodAuthStatus=2)
Starting Dose
400 U
Dose Levels
400 U (Main Period); up to 800 U (Open Label Extension)
Frequency
Single treatment cycle in Main Period; Open-label extension: 4-5 treatment cycles (if indicated)
Maximum Dose
800 U
Dose Escalation Increase
Initial 400 U, subsequent dosing up to 800 U in open-label extension
Investigational Product Name
Placebo to NT 201
Modality
Other
Routes Of Administration
Intramuscular injection (placebo)
Route
Intramuscular injection
Frequency
Single treatment cycle in Main Period
Combination Treatment
Yes

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