Clinical Trials

Inclusion Criteria: 

• At least 18 years of age, at the time of signing the informed consent.
•  Participant has a diagnosis of CM with or without aura according to ICHD–34 criteria for ≥ 12 months.
• Participant age < 50 years at the time of migraine onset.
• Participant meeting the following headache and migraine day criteria in each of the 3 months prior to screening:
  • History of ≥ 15 headache days5 per month
  • History of ≥ 8 migraine days5 per month.
•  During the last 28 days of the screening period, participant experiencing:
  • ≥ 15 headache days5
  • ≥ 8 migraine days5  that qualify as such per the headache diary.
• At least 3 headache-free days in each of the last 3 months prior to screening.
• At least 3 headache-free days during the last 28 days of the screening period.
• Participant completed at least 24 out of 28 days in the headache diary during the last 28 days of the screening period.
• If treated with direct anticoagulants: absence of significant bleeding events for 6 months prior to screening.
• If treated with vitamin K antagonists (coumarins) or other anticoagulants monitored by INR: INR ≤ 3.0.
• Participant is willing and able to comply with the requirements of the study protocol (including all required assessments, especially eCOA tasks) and the instructions of the study site staff.
• Participant having a sexual relationship in which the participant or the partner may become pregnant is willing to use contraceptive method(s) according to local regulations. Participants of childbearing potential6 must be using a highly effective method of birth control.
• Negative result in a pregnancy test (participants of childbearing potential only)
• Written informed consent obtained from the participant.

Exclusion Criteria:

• Any factor that in the investigator’s opinion is likely to compromise the ability of the participant to take part in the trial.
• Suicidal ideations or behavior in the clinical judgment of the investigator.
• Any of the following:
  • Known hypersensitivity to Xeomin, or any of its formulation ingredients
  • Known hypersensitivity to any other BoNT/A product
  • Previous nonresponse to BoNT-treatment for any indication despite appropriate dose.
• Any skin disorders that might compromise the therapeutic technique and safety (e.g., localized infection in the area of injections) 
• Diagnosis of other primary headache types, except tension-type headache, which is permitted.
• 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.
• Diagnosis of secondary headache types, except medication overuse headache, which is permitted.
• Any other clinically significant pain syndrome that, in the judgment of the investigator, may confound the participant’s ability to assess headache / migraine episodes (e.g., fibromyalgia, complex regional pain syndrome, etc.) 
• 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 trial and the trial intervention.
• Known severe substance use disorder (e.g., alcohol, cannabis products for medical or recreational purposes, illegal drugs, hypnotics, sedatives, anxiolytics) within the past 2 years or currently ongoing according to investigator assessment.
•  Known significant neurological or psychiatric disorders that could, according to the investigator’s assessment, interfere with headache/migraine assessment (e.g., major depression, major anxiety disorder, psychosis, severe personality disorder) 
•  Ongoing severe or uncontrolled disease (including active malignancies or high risk of recurrence of malignancies) that, in the judgment of the investigator, may put the participant at significant risk, may interfere with the trial, or may impede completion of the trial.
• Use of any of the following therapies or interventions in the area of the head or neck, for the treatment of headache/migraine within 1 month prior to screening or plans to receive any of these during the trial:
  • Extracranial nerve block
  • Cervical facet injection
  • Transcranial magnetic stimulation, neuromodulation, or neurostimulation (at any part of the body)
  • Radiofrequency ablation
  • Injections or dry needling of trigger points
  • Acupuncture
  • Other approved devices or interventional procedures for headache/migraine.
•  Participant who has received migraine surgery (e.g., decompression of the occipital nerve) at any time prior to the trial or is planning to do so during the trial.
•  Use of the following drugs or products containing these drugs on > 4 days during any month of the last 3 months prior to screening or during the screening period:
  • Opioids
  • Barbiturates.
• Current or planned treatment with local anesthetics in the head or neck region, or treatment with drugs that interfere with neuromuscular transmission, such as aminoglycoside antibiotics or tubocurarine-type muscle relaxants.
• In a dependent relationship with the investigator, the sponsor, or other parties involved in the conduct of the trial (e.g., employee or direct relative of an employee of the CRO, the trial site, or Merz) 

Prior / concomitant therapy

• Use of BoNT therapy for any reason (medical or aesthetic) within 6 months prior to screening or intended treatment during the trial.
• History of inadequate response9 to > 3 medications (of which 2 have different modes of action) for the preventive treatment of migraine.
• Currently taking > 1 prescribed drug for the preventive treatment of migraine.
• Participant receiving fremanezumab (Ajovy®) or eptinezumab (Vyepti®) in 3‑month intervals.
• Participant having discontinued or changed a drug for the preventive treatment of migraine13 (agent and/or dosing) within 3 months prior to screening or with an intended change during the trial.
• Participant who has discontinued anti-CGRP (receptor) mAb treatment less than 5 months prior to screening.

Prior / concurrent clinical trial experience 

• Participation in an interventional clinical trial within the last 6 months prior to screening or intended participation during the trial.
• Prior participation in a clinical trial that investigated BoNT for the treatment of migraine within the last 2 years.
• Previous randomization in this clinical trial.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 4/16/2025. Questions regarding updates should be directed to the study team contact.