Clinical trial • Phase III • Neurology

CLOSTRIDIUM BOTULINUM NEUROTOXIN TYPE A (150KD), FREE OF COMPLEXING PROTEINS (IncobotulinumtoxinA) for Episodic migraine

Phase III trial of CLOSTRIDIUM BOTULINUM NEUROTOXIN TYPE A (150KD), FREE OF COMPLEXING PROTEINS (IncobotulinumtoxinA) for Episodic migraine.

Overview

Trial Therapeutic Area
Neurology
Trial Disease
Episodic migraine
Trial Stage
Phase III
Drug Modality
Peptide/protein/enzyme

Key dates

Initial CTIS Submission Date
15-05-2025
First CTIS Authorization Date
01-09-2025

Trial design

Randomised, placebo injections at pericranial and cervical points (placebo to clostridium botulinum neurotoxin type a (150 kd)). arms: xeomin dose a (xeomin injections at pericranial and cervical points), xeomin dose b (xeomin injections at pericranial and cervical points), placebo injections at pericranial and cervical points.-controlled Phase III trial in Germany, Austria, Italy and others.

Randomised
Yes
Comparator
Placebo injections at pericranial and cervical points (Placebo to Clostridium Botulinum neurotoxin type A (150 kD)). Arms: Xeomin Dose A (Xeomin injections at pericranial and cervical points), Xeomin Dose B (Xeomin injections at pericranial and cervical points), Placebo injections at pericranial and cervical points.
Target Sample Size
333

Eligibility

Recruits 333 Vulnerable population selection flagged (isVulnerablePopulationSelected = true). Study includes specific pregnancy/newborn informed consent forms (documents titled 'Pregnancy-and-Newborn-ICF', 'Pregnant-Partner-ICF' and country-specific pregnancy/newborn ICFs listed among study documents). All participants must be ≥18 years and provide informed consent per the Main-ICF documents. No further explicit assent/consent handling text is provided in the JSON..

Vulnerable Population
Vulnerable population selection flagged (isVulnerablePopulationSelected = true). Study includes specific pregnancy/newborn informed consent forms (documents titled 'Pregnancy-and-Newborn-ICF', 'Pregnant-Partner-ICF' and country-specific pregnancy/newborn ICFs listed among study documents). All participants must be ≥18 years and provide informed consent per the Main-ICF documents. No further explicit assent/consent handling text is provided in the JSON.

Inclusion criteria

  • {"criterion_text":"- At least 18 years of age, at the time of signing the informed consent;\n- Participant has a diagnosis of EM with or without aura according to current International Classification of Headache Disorders (Edition 3 and Edition 4 alpha) criteria for ≥ 12 months and is able to distinguish migraine headaches from all other types of headaches;\n- Participant age < 50 years at the time of migraine onset;\n- Participant meeting the following headache and migraine day criteria in each of the 3 months prior to screening: history of ≤ 14 headache days per month and history of 6 to 14 migraine days per month; and\n- During the last 28 days of the screening period, participant experiencing: ≤ 14 headache days and 6 to 14 migraine days that qualify as such per the headache diary."}

Exclusion criteria

  • {"criterion_text":"- Diagnosis of chronic migraine;\n- Diagnosis of other primary headache types, except tension-type headache, which is permitted;\n- Diagnosis of aura without headache, migraine with brainstem aura, hemicrania continua, hypnic headache, hemiplegic migraine, retinal migraine, persistent aura without infarction, migraine aura-triggered seizure, or previous migrainous infarction;\n- Diagnosis of secondary headache types, except medication overuse headache, which is permitted;\n- Currently taking > 1 prescribed drug for the preventive treatment of migraine;\n- Discontinuation of anti-calcitonin gene-related peptide (CGRP) / anti-CGRP receptor monoclonal antibody treatment less than 5 months prior to screening."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Change in monthly migraine days from baseline (28 days before baseline visit) to Month 6 (weeks 21 to 24 after first injection) – Dose A.","definition_or_measurement_approach":"Change from baseline (baseline defined as 28 days before baseline visit) in monthly migraine days measured at Month 6 (weeks 21–24 after first injection); comparison Dose A vs Placebo."}

Secondary endpoints

  • {"endpoint_text":"- Change in monthly migraine days from baseline (28 days before baseline visit) to Month 6 (weeks 21 to 24 after first injection) – Dose B.","definition_or_measurement_approach":"Change from baseline in monthly migraine days measured at Month 6 (weeks 21–24 after first injection); comparison Dose B vs Placebo."}
  • {"endpoint_text":"- Change in monthly headache days from baseline (28 days before baseline visit) to Month 6 (weeks 21 to 24 after first injection) – Dose A.","definition_or_measurement_approach":"Change from baseline (28 days before baseline visit) in monthly headache days measured at Month 6 (weeks 21–24 after first injection) for Dose A."}
  • {"endpoint_text":"- Change in monthly headache days from baseline (28 days before baseline visit) to Month 6 (weeks 21 to 24 after first injection) – Dose B.","definition_or_measurement_approach":"Change from baseline in monthly headache days measured at Month 6 (weeks 21–24 after first injection) for Dose B."}
  • {"endpoint_text":"- Change in monthly acute migraine medication days from baseline (28 days before baseline visit) to Month 6 (weeks 21 to 24 after first injection) – Dose A.","definition_or_measurement_approach":"Change from baseline in monthly days using acute migraine medication measured at Month 6 (weeks 21–24 after first injection) for Dose A."}
  • {"endpoint_text":"- Change in monthly acute migraine medication days from baseline (28 days before baseline visit) to Month 6 (weeks 21 to 24 after first injection) – Dose B.","definition_or_measurement_approach":"Change from baseline in monthly days using acute migraine medication measured at Month 6 (weeks 21–24 after first injection) for Dose B."}
  • {"endpoint_text":"- Change in frequency of migraine days from baseline (baseline monthly migraine days divided by 2) to two-week end-of-cycle periods (weeks 11 and 12 of Cycle 1 to 4).","definition_or_measurement_approach":"Change from baseline frequency (baseline monthly migraine days/2) to two-week end-of-cycle periods (weeks 11 and 12 of Cycles 1–4)."}
  • {"endpoint_text":"- Percentage of participants who reported at least a 50% reduction in mean monthly migraine days from baseline (28 days before baseline visit) to Month 6 (weeks 21 to 24 after first injection).","definition_or_measurement_approach":"Responder rate defined as ≥50% reduction in mean monthly migraine days from baseline to Month 6 (weeks 21–24 after first injection)."}
  • {"endpoint_text":"- Incidence of treatment‑emergent adverse events (TEAEs) related to treatment as assessed by the investigator in the placebo-controlled period (PCP).","definition_or_measurement_approach":"Investigator-assessed incidence of treatment-emergent adverse events related to treatment during the placebo-controlled period."}

Recruitment

Registry Or Advocacy Recruitment
True: 'Site-and-Patient-Advocacy-Contact-List-for-ICF' document referenced (specific advocacy or registry group names not enumerated in the JSON).
Planned Sample Size
333
Recruitment Window Months
32
Consent Approach
Informed consent obtained from adult participants (minimum age 18 per inclusion criteria). Main informed consent forms (Main-ICF) and pregnancy/newborn ICFs are provided; country- and language-specific ICFs listed (German/AT, Italian, Spanish, Polish, Slovak, French, Czech, Danish, English versions referenced). Contact for queries provided (functional email ctis@merz.de). No additional assent procedures for minors are applicable because participants must be ≥18.

Methods

  • Site-based recruitment via participating neurology clinics and hospital departments (multiple country-specific site materials listed).
  • Doctor-to-patient letters / GP letters to invite potentially eligible patients (documents: Doctor-to-patient-letter, GP_Letter).
  • On-site posters, flipcharts, recruitment brochures and patient letters (documents: Poster, Flipchart, Recruitment-Brochure, Patient-Letter) in country-specific versions.
  • Study staff / clinic referral and site outreach (recruitment procedures documents K1/K2 for multiple countries).

Geography

Total Number Of Sites
60
Total Number Of Participants
649

Germany

Earliest CTIS Part Ii Submission Date
22-08-2025
Latest Decision Or Authorization Date
03-09-2025
Processing Time Days
12
Number Of Sites
6
Number Of Participants
65

Sites

Site Name
Universitaetsmedizin Greifswald KöR
Department Name
Klinik und Poliklinik für Neorologie
Contact Person Name
Robert Fleischmann
Site Name
Vitos Orthopaedische Klinik Kassel gGmbH
Contact Person Name
Miriam Butz
Contact Person Email
miriam.butz@vitos-okk.de
Site Name
Studienzentrum Nord-West
Contact Person Name
Joachim Springub
Contact Person Email
joachim.springub@ewetel.net
Site Name
Schmerzklinik Kiel Gmbh & Co. KG Klinik fuer neurologisch-verhaltensmedizinische Schmerztherapie
Contact Person Name
Hartmut Göbel
Contact Person Email
hg@schmerzklinik.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Klinik für Neurologie
Contact Person Name
Bianca Raffaelli
Contact Person Email
kopfschmerz@charite.de
Site Name
Kopfschmerzzentrum Frankfurt
Contact Person Name
Charly Gaul

Austria

Earliest CTIS Part Ii Submission Date
25-07-2025
Latest Decision Or Authorization Date
05-09-2025
Processing Time Days
42
Number Of Sites
2
Number Of Participants
12

Sites

Site Name
Landeskrankenanstalten-Betriebsgesellschaft Kabeg
Department Name
Neurologie
Contact Person Name
Sonja- Maria Tesar
Contact Person Email
Sonja-Maria.Tesar@kabeg.at
Site Name
Medizinische Universitaet Innsbruck
Department Name
Univ.-Klinik für Neurologie
Contact Person Name
Gregor Brössner
Contact Person Email
Gregor.broessner@i-med.ac.at

Italy

Earliest CTIS Part Ii Submission Date
26-06-2025
Latest Decision Or Authorization Date
10-10-2025
Processing Time Days
106
Number Of Sites
5
Number Of Participants
43

Sites

Site Name
Istituto Auxologico Italiano
Department Name
UO Neurologia – Clinical Trial Center
Contact Person Name
Alberto Doretti
Contact Person Email
a.doretti@auxologico.it
Site Name
Ospedale San Raffaele S.r.l.
Department Name
UOC Neurologia
Contact Person Name
Massimo Filippi
Contact Person Email
filippi.massimo@hsr.it
Site Name
Azienda Ospedaliero Universitaria Careggi
Department Name
Centro Cefalee e Farmacologia Clinica
Contact Person Name
Alberto Chiarugi
Contact Person Email
lberto.chiarugi@unifi.it
Site Name
Fondazione Istituto Neurologico Nazionale Casimiro Mondino
Department Name
Brain and Behavioral Sciences
Contact Person Name
Cristina Tassorelli
Contact Person Email
cristina.tassorelli@mondino.it
Site Name
Irccs San Raffaele Roma S.r.l.
Department Name
Unità per la cura e la ricerca su cefalee e dolore
Contact Person Name
Piero Barbanti
Contact Person Email
piero.barbanti@sanraffaele.it

Denmark

Earliest CTIS Part Ii Submission Date
02-06-2025
Latest Decision Or Authorization Date
22-10-2025
Processing Time Days
142
Number Of Sites
2
Number Of Participants
21

Sites

Site Name
Odense University Hospital
Department Name
Department of Neurology
Contact Person Name
Dagmar Beier
Contact Person Email
dagmar.beier@rsyd.dk
Site Name
Rigshospitalet
Department Name
Danish Headache Center, Department of Neurology
Contact Person Name
Henrik Schytz
Contact Person Email
hovedpine@regionh.dk

Slovakia

Earliest CTIS Part Ii Submission Date
07-07-2025
Latest Decision Or Authorization Date
15-12-2025
Processing Time Days
161
Number Of Sites
4
Number Of Participants
68

Sites

Site Name
Neures s.r.o.
Department Name
Neurologická ambulancia
Contact Person Name
Renáta Smiková
Contact Person Email
renata.smikova@gmail.com
Site Name
Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu Liptovsky Mikulas
Department Name
Neurologické oddelenie
Contact Person Name
Michal Kováčik
Contact Person Email
kovacik@nsplm.sk
Site Name
MUDr. Beata Dupejova neurologicka ambulancia s.r.o.
Contact Person Name
Beáta Dupejová
Contact Person Email
dupejova@gmail.com
Site Name
Konzilium s.r.o.
Contact Person Name
Magdaléna Perichtová
Contact Person Email
perichtova.md@gmail.com

Poland

Earliest CTIS Part Ii Submission Date
02-06-2025
Latest Decision Or Authorization Date
17-11-2025
Processing Time Days
168
Number Of Sites
19
Number Of Participants
265

Sites

Site Name
Pratia S.A.
Contact Person Name
Katarzyna Kasprzyk
Contact Person Email
kkasprzyk-galon@pratia.pl
Site Name
ETG Lublin Sp. z o.o.
Contact Person Name
Barbara Pietruszewska
Site Name
MIGRE Polskie Centrum Leczenia Migreny ANNA GRYGLAS-DWORAK
Contact Person Name
Anna Gryglas-Dworak
Contact Person Email
anna.gryglas@gmail.com
Site Name
Krakowska Akademia Neurologii Sp. z o.o.
Contact Person Name
Monika Rudzińska-Bar
Contact Person Email
mrudzinska-bar@uafm.edu.pl
Site Name
Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. S.K.
Contact Person Name
Magdalena Boczarska-Jedynak
Site Name
Clinirem Sp. z o.o.
Contact Person Name
Urszula Chyrchel-Paszkiewicz
Contact Person Email
pgluchyrchel@gmail.com
Site Name
Silmedic Sp. z o.o.
Contact Person Name
Ilona Pałka-Kisielowska
Contact Person Email
silmedic@silmedic.pl
Site Name
ETG Lublin Sp. z o.o. (alternate site)
Contact Person Name
Dominika Tomaka
Contact Person Email
d.tomaka@etg-network.com
Site Name
Etg Zamosc Sp. z o.o.
Contact Person Name
Kajetan Mazurek
Contact Person Email
kajetan.mazurek@gmail.com
Site Name
Neurocor Banaszkiewicz Tomaszewski Lekarze sp.p.
Contact Person Name
Krzysztof Banaszkiewicz
Contact Person Email
krzysztof@banaszkiewicz.ne
Site Name
Athleticomed Sp. z o.o.
Contact Person Name
Magdalena Nowaczewska
Contact Person Email
k.nowaczewski@athleticomed.pl
Site Name
Futuremeds Sp. z o.o. (Cracow)
Contact Person Name
Karolina Porębska
Site Name
Etg Neuroscience Sp. z o.o.
Contact Person Name
Aleksandra Karbowniczek
Site Name
Futuremeds Sp. z o.o. (Wroclaw)
Contact Person Name
Aleksandra Herrera-Sokołowska
Site Name
Indywidualna Praktyka Lekarska Dr hab. med. Anna Szczepańska-Szerej
Contact Person Name
Anna Szczepańska-Szerej
Contact Person Email
aszerej@poczta.onet.pl
Site Name
Solumed Sp. z o.o. sp.k.
Contact Person Name
Olgierd Stefański
Contact Person Email
olgierd_stefanski@interia.pl
Site Name
Pratia S.A. (Gdynia)
Contact Person Name
Iwo Sługocki
Contact Person Email
islugocki@pratia.pl
Site Name
Centrum Medyczne Neuromed Sp. z o.o.
Contact Person Name
Paweł Lisewski
Contact Person Email
lisewski.p@gmail.com
Site Name
Jan Banach Research Spot
Contact Person Name
Lucyna Horodecka Wardęga

Spain

Earliest CTIS Part Ii Submission Date
04-07-2025
Latest Decision Or Authorization Date
17-10-2025
Processing Time Days
105
Number Of Sites
13
Number Of Participants
107

Sites

Site Name
Hospital Universitario Regional De Malaga
Department Name
Neurology Department
Contact Person Name
Lucia de Flores Garcia Trujillo
Contact Person Email
floreslucia78@hotmail.com
Site Name
Consorci Sanitari De Terrassa
Department Name
Neurology Department
Contact Person Name
Gabriel Salazar Tortolero
Contact Person Email
GSalazar@CST.CAT
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Neurology Department
Contact Person Name
Carmen Gonzalez Oria
Contact Person Email
carmengoria@hotmail.com
Site Name
Hospital Clinic De Barcelona
Department Name
Neurology Department
Contact Person Name
Victor Obach
Contact Person Email
vobach@clinic.cat
Site Name
Fundación Neuropolis
Department Name
Neurology Department
Contact Person Name
Antonio Oliveros-Cid
Site Name
Hospital Alvaro Cunqueiro
Department Name
Neurology Department
Contact Person Name
Maria Dolores García Bargo
Site Name
Hospital Blua Sanitas Valdebebas
Department Name
Neurology
Contact Person Name
Angel Aledo Serrano
Contact Person Email
as.aledo@gmail.com
Site Name
Hospital Universitario La Paz
Department Name
Neurology Department
Contact Person Name
Javier Diaz de Terán Velasco
Contact Person Email
javierddt@gmail.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Neurology Department
Contact Person Name
Patricia Pozo Rosich
Contact Person Email
patricia.pozo@vhir.org
Site Name
Hospital Vithas Parque San Antonio
Department Name
Neurology Department
Contact Person Name
Maria Victoria Castro
Contact Person Email
v.castro.eecc@gmail.com
Site Name
Hospital Universitario 12 De Octubre
Department Name
Neurology Department
Contact Person Name
Alejandro Herrero San Martín
Contact Person Email
alexportalrubio@hotmail.com
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Neurology Department
Contact Person Name
Samuel Diaz Insa
Contact Person Email
sdiazinsa@yahoo.es
Site Name
Hospital Universitario Virgen De La Victoria
Department Name
Neurology Department
Contact Person Name
Omar Hamad Cueto
Contact Person Email
ohacu@gmail.com

Czechia

Earliest CTIS Part Ii Submission Date
12-09-2025
Latest Decision Or Authorization Date
19-11-2025
Processing Time Days
68
Number Of Sites
6
Number Of Participants
56

Sites

Site Name
Pratia Brno s.r.o.
Contact Person Name
Jitka Grohová
Contact Person Email
grohova@tiscali.cz
Site Name
CLINTRIAL s.r.o.
Contact Person Name
Miroslava Chýlova
Contact Person Email
m.chylova@clintrial.cz
Site Name
Neuropsychiatrie s.r.o.
Contact Person Name
Jakub Hort
Contact Person Email
neuropsychiatrie@gmail.com
Site Name
Fakultní nemocnice Hradec Králové
Department Name
Neurologická klinika
Contact Person Name
Zbyšek Pavelek
Contact Person Email
zbysek.pavelek@fnhk.cz
Site Name
Axon Clinical s.r.o.
Contact Person Name
Zuzana Matoušová
Contact Person Email
zuzmat62@gmail.com
Site Name
NeuroMed Zlín s.r.o.
Department Name
Neurologická ambulance
Contact Person Name
Monika Záhumenská
Contact Person Email
zahumenska@seznam.cz

France

Earliest CTIS Part Ii Submission Date
02-06-2025
Latest Decision Or Authorization Date
28-10-2025
Processing Time Days
148
Number Of Sites
3
Number Of Participants
12

Sites

Site Name
University Hospital Of Clermont-Ferrand
Department Name
Neurology
Contact Person Name
Xavier MOISSET
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Integrative medicine department
Contact Person Name
Emmanuelle BOUGOUIN-KUHN
Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
Neurology
Contact Person Name
Mathieu VAILLANT
Contact Person Email
MVaillant@chu-grenoble.fr

Sponsor

Primary sponsor

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

Contract research organisations

Name
PPD Global Limited
Responsibilities
sponsorDuties codes: [1,12,2,5,6,8]
Name
Pharmaceutical Product Development LLC
Responsibilities
sponsorDuties codes: [4]
Name
Almac Clinical Services (Ireland) Limited
Responsibilities
sponsorDuties codes: [14]
Name
Almac Clinical Services Limited
Responsibilities
sponsorDuties codes: [14]
Name
Almac Clinical Technologies LLC
Responsibilities
sponsorDuties codes: [3]

Third parties

  • {"country":"Germany","full_name":"Eurofins BioPharma Product Testing Munich GmbH","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Almac Clinical Services (Ireland) Limited","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"PPD Global Limited","duties_or_roles":"sponsorDuties codes: [1,12,2,5,6,8]","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"sponsorDuties codes: [7]","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"sponsorDuties codes: [3]","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Toxologics GmbH","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Infraserv GmbH & Co. Hoechst KG","duties_or_roles":"sponsorDuties codes: [15] (24 hours emergency unblinding service and hotline)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
CLOSTRIDIUM BOTULINUM NEUROTOXIN TYPE A (150KD), FREE OF COMPLEXING PROTEINS
Active Substance
CLOSTRIDIUM BOTULINUM NEUROTOXIN TYPE A (150KD), FREE OF COMPLEXING PROTEINS (IncobotulinumtoxinA)
Modality
Peptide/protein/enzyme
Routes Of Administration
INTRAMUSCULAR INJECTION
Route
Intramuscular injection
Authorisation Status
prodAuthStatus: 2; marketingAuthNumber: '-'
Maximum Dose
maxDailyDoseAmount: 195 U unit(s); maxTotalDoseAmount: 780 U unit(s)
Investigational Product Name
Placebo to Clostridium Botulinum neurotoxin type A (150 kD)
Modality
Other

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