CLOSTRIDIUM BOTULINUM, NEUROTOXIN SEROTYPE A/B for Episodic migraine | Chronic migraine

Inclusion criteria

• {"criterion_text":"- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF. Participant has provided written informed consent and signed privacy/data protection documentation"}
• {"criterion_text":"- Male or female ≥18 to 80 years of age at the time of signing the informed consent"}
• {"criterion_text":"- Diagnosis of either EM or CM, per ICHD-3 criteria, for at least 12 months prior to the screening visit"}
• {"criterion_text":"- Diagnosis of migraine at ≤50 years of age"}
• {"criterion_text":"- Participants in the EM group: History of EM diagnosis and headache frequency (i.e. migraine and non-migraine headache): ≤14 headache days in the 4 weeks prior to randomisation on study Day 1 based on information recorded in the eDiary; migraine frequency: ≥6 migraine days in the 4 weeks prior to randomisation on study Day 1 based on information recorded in the eDiary;"}
• {"criterion_text":"- Participants in the CM group: History of CM diagnosis and headache frequency (i.e. migraine and non-migraine headache): ≥15 headache days in the 4 weeks prior to randomisation on study Day 1 based on information recorded in the eDiary; migraine frequency: ≥8 migraine days in the 4 weeks prior to randomisation on study Day 1 based on information recorded in the eDiary;"}
• {"criterion_text":"- Participant with a history of use of at least one preventive treatment for migraine for at least 8 weeks prior to the screening visit"}

Exclusion criteria

• {"criterion_text":"- History or current diagnosis of migraine with brainstem aura, retinal migraine, complications of migraine, tension-type headache, trigeminal autonomic cephalalgias, hypnic headache, hemicrania continua or new daily persistent headache"}
• {"criterion_text":"- A diagnosis of a neuromuscular disorder or respiratory disorder, such as myasthenia gravis, Lambert-Eaton syndrome or amyotrophic lateral sclerosis that in the opinion of the investigator would compromise the safety of the study participant"}
• {"criterion_text":"- Headache attributed to another disorder (e.g. secondary headaches), except medication overuse headache (MOH)"}
• {"criterion_text":"- Current uncontrolled psychiatric or psychological condition, or one that could confound assessment of headaches/migraines or interfere with study participation"}
• {"criterion_text":"- Risk of self-harm or harm to others as evidenced by past suicidal behaviour or endorsing items 3, 4, or 5 on the C-SSRS at Screening or Day 1 (except for France)."}
• {"criterion_text":"- Participants presenting with a swallowing disorder of any origin which might be exacerbated by botulinum toxin treatment, such as: - Grade 3 or 4 on the Dysphagia Severity Scale (severe dysphagia) with swallowing difficulties and requiring a change in diet."}
• {"criterion_text":"- Clinically relevant skin condition or infection that could interfere with injection of study intervention"}
• {"criterion_text":"- Participant has any medical condition or situation that would make them unsuitable for participation in the study"}
• {"criterion_text":"- Participant receiving more than one allowable concomitant migraine preventive treatment"}
• {"criterion_text":"- Known history of an inadequate response to >4 medications prescribed for the prevention of migraine (2 of which have different mechanisms of action to botulinum toxin)"}
• {"criterion_text":"- Body mass index (BMI) ≥35 kg/m² at the screening visit"}
• {"criterion_text":"- Use of any of the following medications in the specified timeframe prior to the screening visit: - Botulinum toxin for migraine within 24 weeks (or for any other medical/aesthetic reason within 16 weeks); - Prior use of mAbs blocking CGRP pathway within 12 weeks for preventative treatment of migraine; - Prior use of oral CGRP receptor antagonist (gepants) for preventative treatment of migraine within 2 weeks; - Anaesthetic or steroid injection in any region targeted for treatment with study medication within 4 weeks; - Use of cannabidiol or other types of cannabinoids within 30 days; - Use of medical device to treat migraine within 4 weeks (e.g. non-invasive neuromodulation therapies such as nerve stimulation (gammaCore), transcranial magnetic stimulation (cephaly), external trigeminal nerve stimulation, transcutaneous electrical nerve stimulation and peripheral neuroelectrical stimulation); - Use of other intervention to treat migraine that is assessed to interfere with study evaluations within 4 weeks (e.g. acupuncture in the face, head and neck region, cranial traction, nociceptive trigeminal inhibition, occipital nerve block treatments and dental splints for headache); - Use of opioids or barbiturates for more than 2 days/month within the last 4 weeks."}
• {"criterion_text":"- Participation in another interventional clinical study or use of any treatment with an experimental drug within 30 days or within five times the documented terminal half-life of the respective drug or its metabolites (if the half-life is unknown, within 30 days) prior to the screening visit and during the conduct of the study"}
• {"criterion_text":"- Diagnosis of fibromyalgia or other significant pain disorders that could confound the assessment of headaches/migraines or interfere with study participation, including but not limited to chronic pain disorders such as chronic low back pain and complex regional pain syndrome"}
• {"criterion_text":"- Pregnant women, nursing women, premenopausal women, or WOCBP (i.e. not surgically sterile or 1 year postmenopausal) not willing to practice an acceptable contraceptive method at the beginning of the study, and for a minimum of 12 weeks following the administration of study treatment"}
• {"criterion_text":"- Male subjects who are not vasectomised and who have female partners of childbearing potential and are not willing to use condoms with or without spermicide for a minimum of 12 weeks following the initial double-blind administration of the treatment"}
• {"criterion_text":"- History of alcohol or drug abuse within 5 years of the screening visit (excluding medication overuse for headache)"}
• {"criterion_text":"- Known clinically significant hypersensitivity to any of the study drugs, excipients or materials used to administer the study drug;"}
• {"criterion_text":"- Patients who, in the clinician’s judgment, are actively suicidal, and therefore, deemed to be at significant risk for suicide"}

Primary endpoints

• {"endpoint_text":"- Percentage of participants experiencing any Adverse Event (AEs) including treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse event of special interest (AESI) and AE leading to treatment discontinuation [ Time Frame: For step 1: From baseline until end of study at Week 36 ]","definition_or_measurement_approach":"Assessment of any AEs (TEAEs, SAEs, AESI and AEs leading to treatment discontinuation) from baseline until Week 36 (for Step 1)."}
• {"endpoint_text":"- Percentage of Participants with clinically significant changes from baseline in Laboratory Parameters [ Time Frame: For step 1: At all timepoints post injection until Week 36 ] Clinically significant change in laboratory parameters will be reported. The clinical significance will graded by the investigator.","definition_or_measurement_approach":"Clinically significant laboratory parameter changes reported at all post-injection timepoints until Week 36; clinical significance graded by the investigator."}
• {"endpoint_text":"- Percentage of Participants With Clinically Significant Changes from baseline in Vital Signs [ Time Frame: For step 1: At all timepoints post injection until Week 36 ] Clinically significant changes in vital signs will be reported. The clinical significance will be graded by the investigator.","definition_or_measurement_approach":"Clinically significant changes in vital signs assessed at all post-injection timepoints until Week 36; clinical significance graded by the investigator."}
• {"endpoint_text":"- Percentage of participants with clinically significant change from baseline in facial examination [ Time Frame: For step 1: At all timepoints post injection until Week 36 ] Clinically significant changes in facial examination and focused neurological/physical examinations will be reported. The clinical significance will be graded by the investigator.","definition_or_measurement_approach":"Clinically significant changes in facial and focused neurological/physical examinations assessed at all post-injection timepoints until Week 36; clinical significance graded by the investigator."}
• {"endpoint_text":"- Percentage of participants with clinically significant change from baseline in 12-lead Electrocardiogram (ECG) readings [ Time Frame: For step 1: At all timepoints post injection until Week 36 ]","definition_or_measurement_approach":"Clinically significant 12-lead ECG changes assessed at all post-injection timepoints until Week 36."}
• {"endpoint_text":"- Treatment-emergence of suicidal ideation/suicidal behaviour [ Time Frame: For step 1: At all timepoints post injection until Week 36 ]","definition_or_measurement_approach":"Assessment of emergence of suicidal ideation/behaviour at all post-injection timepoints until Week 36."}
• {"endpoint_text":"- Percentage of participants with Binding antibodies to IPN10200 [ Time Frame: For step 1: At baseline, Week 4, Week 12 and Week 36. ]","definition_or_measurement_approach":"Binding anti-drug antibodies measured at baseline, Week 4, Week 12 and Week 36 (Step 1)."}
• {"endpoint_text":"- Percentage of participants with neutralising antibodies to IPN10200 [ Time Frame: For step 1: At baseline, Week 4, Week 12 and Week 36. ]","definition_or_measurement_approach":"Neutralising anti-drug antibodies measured at baseline, Week 4, Week 12 and Week 36 (Step 1)."}
• {"endpoint_text":"- Change from baseline in the number of Monthly migraine days (MMD)s [ Time Frame: For step 2: At Week 12 (Weeks 9-12). ]","definition_or_measurement_approach":"Change in monthly migraine days from baseline assessed at Week 12 (weeks 9-12) for Step 2."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in the number of MMD [ Time Frame: For Step 1 and step 2: From Week 1 to Week 36. ]","definition_or_measurement_approach":"Change in monthly migraine days from baseline assessed weekly / across Weeks 1–36 for Steps 1 and 2."}
• {"endpoint_text":"- Change from baseline in the number of Monthly Headache Days (MHD) [ Time Frame: For Step 1 and step 2: From Week 1 to Week 36 ]","definition_or_measurement_approach":"Change in monthly headache days from baseline assessed from Week 1 to Week 36."}
• {"endpoint_text":"- Change from baseline in the number of moderate/severe MHD [ Time Frame: For Step 1 and step 2: From Week 1 to Week 36 ]","definition_or_measurement_approach":"Change in number of moderate/severe monthly headache days from baseline assessed Weeks 1–36."}
• {"endpoint_text":"- Migraine prevention response [ Time Frame: For Step 1 and step 2: From Week 1 to Week 36 ] Migraine prevention response is assessed using two thresholds: by a reduction from baseline of either ≥50% or ≥75% in MMD","definition_or_measurement_approach":"Response defined as ≥50% or ≥75% reduction from baseline in monthly migraine days, assessed Weeks 1–36."}
• {"endpoint_text":"- Headache prevention response [ Time Frame: For Step 1 and step 2: From Week 1 to Week 36. ] Assessed using two thresholds: by a reduction from baseline of either ≥50% or ≥ 75% in MHD","definition_or_measurement_approach":"Response defined as ≥50% or ≥75% reduction from baseline in monthly headache days, assessed Weeks 1–36."}
• {"endpoint_text":"- Change from baseline in the number of days per 4 week period of acute medication use for migraine relief. [ Time Frame: For Step 1 and step 2: From Week 1 to Week 36. ] An acute medication use day is defined as any day on which a participant reports, per eDiary, the intake of allowed medication(s) for the acute treatment of migraine.","definition_or_measurement_approach":"Change in number of days per 4-week period with acute medication use as recorded in daily eDiary from Week 1 to Week 36. An acute medication use day = any day participant reports intake of allowed acute migraine medication in eDiary."}
• {"endpoint_text":"- The use of acute migraine medication (yes or no) [ Time Frame: For Step 1 and step 2: From Week 1 to Week 36. ] The use of acute migraine medication will be recorded in the daily eDiary.","definition_or_measurement_approach":"Binary recording of any acute migraine medication use per day captured via daily eDiary from Week 1 to Week 36."}
• {"endpoint_text":"- Percentage of participants with Binding antibodies to IPN10200 [ Time Frame: For step 2 : At baseline, Week 4, Week 12 , Week 24 and Week 36. ]","definition_or_measurement_approach":"Binding anti-drug antibodies measured at baseline, Week 4, Week 12, Week 24 and Week 36 (Step 2)."}
• {"endpoint_text":"- Percentage of participants with neutralising antibodies to IPN10200 [ Time Frame: For step 2 : At baseline, Week 4, Week 12 , Week 24 and Week 36. ]","definition_or_measurement_approach":"Neutralising anti-drug antibodies measured at baseline, Week 4, Week 12, Week 24 and Week 36 (Step 2)."}

Methods

• Country-specific recruitment brochures (documents: K2_* Recruitment Brochure) — patient-facing brochures in Czech, French, German, Spanish, Polish.
• Country-specific recruitment posters (documents: K2_* Recruitment Poster) — posters for display at sites in Czech, France, Germany, Spain, Poland.
• Dear Patient letters (documents: K2_* Recruitment Dear Patient Letter) — country-specific patient invitation letters (Czech, Polish, German).
• Recruitment procedure descriptions and informed consent procedure templates (documents: K1_* Recruitment Procedure Description, K1_* Recruitment and Informed Consent Procedure bilingual) — recruitment workflow and consent procedures described (including bilingual templates).
• Consent navigation and participant guides (documents: K2_* Recruitment Other Cons Nav, Other Participant Guide) — materials to support consent discussions and participant understanding (country-specific).
• Use of site networks and neurology/ headache clinics (trial conducted at neurology departments and specialized headache centers listed per country).

Czechia

Earliest CTIS Part Ii Submission Date

19-06-2025

Latest Decision Or Authorization Date

15-07-2025

Processing Time Days

26

Number Of Sites

3

Number Of Participants

56

France

Earliest CTIS Part Ii Submission Date

18-06-2025

Latest Decision Or Authorization Date

11-07-2025

Processing Time Days

23

Number Of Sites

5

Number Of Participants

64

Germany

Earliest CTIS Part Ii Submission Date

23-06-2025

Latest Decision Or Authorization Date

10-07-2025

Processing Time Days

17

Number Of Sites

10

Number Of Participants

38

Spain

Earliest CTIS Part Ii Submission Date

20-06-2025

Latest Decision Or Authorization Date

16-07-2025

Processing Time Days

26

Number Of Sites

7

Number Of Participants

98

Poland

Earliest CTIS Part Ii Submission Date

19-06-2025

Latest Decision Or Authorization Date

18-07-2025

Processing Time Days

29

Number Of Sites

17

Number Of Participants

55

Primary sponsor

Full Name

Ipsen Innovation

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Parexel International (IRL) Limited

Responsibilities

sponsorDuties codes: 1,10,11,12,13,2,3,4,5,6,7,8,9

Third parties

• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Spain","full_name":"Kymos S.L.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsorDuties codes: 1,10,11,12,13,2,3,4,5,6,7,8,9","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"S-Clinica","duties_or_roles":"sponsorDuties codes: 3","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Eurofins Central Laboratory B.V.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}