A Study to Evaluate the Effectiveness and Safety of Dysport® for the Prevention of Episodic Migraine in Adults

A Phase III, Randomised, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study With Extension Phase to Evaluate the Efficacy and Safety of Dysport® for the Prevention of Episodic Migraine in Adult Participants

The purpose of this study is to understand the safety and effectiveness of the study drug, Dysport® when compared with placebo in preventing episodic migraine.

A migraine is a headache with severe throbbing pain or a pulsating sensation, usually on one side of the head, and is often accompanied by feeling or being sick and a sensitivity to bright lights and sound.

Episodic Migraine is defined as having less than 15 days of headache a month with at least 6 days with migraine headaches.

Migraines are caused by a series of events which cause the brain to get stimulated / activated, which results in the release of chemicals that cause pain.

Dysport® is a formulation of Botulinum toxin type A (BoNT-A), a medication that stops the release of these chemical messengers.

The study will consist of 3 periods:

1. A 'screening period' of 6 to 12 weeks to assess whether the participant can take part to the study and requires 1 visit.

2. A first Treatment Phase of 24 weeks. On Day 1 and at Week 12 of the first Treatment Phase, participants will receive injections into various muscles across the head, neck, face and shoulders.

   The injections will contain either a dose "A" or a dose ''B'' of Dysport® or a placebo (an inactive substance or treatment that looks the same as, and is given in the same way as, an active drug or intervention/treatment being studied).

   Participants will make 4 visits to the clinic in person and have 4 remote (online) visits.

3. A second Treatment Phase of 24 weeks (extension phase). At Week 24 and at Week 36, all participants will get Dysport® (dose "A" or dose "B").

There will be 3 in person visits and 4 remote visits.

Participants will need to complete an e-diary and questionnaires throughout the study.

Participants will undergo blood samplings, urine collections, physical examinations, and clinical evaluations. They may continue some other medications, but the details need to be recorded.

The total study duration for a participant will be up to 60 weeks (approx. 14 months).

Inclusion Criteria :

• Must be ≥18 years of age inclusive, at the time of signing the informed consent and privacy/data protection documentation.
• Participant has a diagnosis for more than 12 months, prior to screening visit, of migraine with aura or migraine without aura according to the International Classification of Headache Disorders definition and diagnostic criteria
• Migraine onset occurred when participant was <50 years of age.
• Has baseline number of monthly headache days (MHD) of <15 and baseline number of monthly migraine days (MMD) of ≥6, using eDiary data collected during the 4 weeks nearest to randomisation on Day 1 (but prior to randomisation).
• Has baseline number of valid diary days ≥22 days collected during the 4 weeks nearest to randomisation on Day 1.
• Participant must have previously used, or is currently using, preventive treatment for migraine (pharmacological) (i.e. non-naïve) prior to start of screening eDiary

Exclusion Criteria :

• 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.

• Headache attributed to another disorder (e.g. secondary headaches), except medication overuse headache, which is permitted.

• Use of any of the following medications in the specified timeframe prior to start of the screening daily headache eDiary:

  a. Within 24 weeks

• i. Botulinum toxin for migraine (or for any other medical/aesthetic reason within 16 weeks)

  b. Within 12 weeks

• i. CGRP antagonists (monoclonal antibody or gepant) for preventive treatment of migraine (acute treatment of headache/migraine with a gepant is permitted, but limited to no more than 6 days per month (i.e. 6 days per each 4-week period with gepant intake))

• ii. Cannabinol or other types of cannabinoids

  c. Within 4 weeks

• i. Anaesthetic or steroid injection in any region targeted for injection with study intervention

• ii. Use of medical device to treat migraine (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)

• iii. Other interventions for migraine assessed to interfere with study evaluations (e.g. acupuncture in head and neck region, cranial traction, nociceptive trigeminal inhibition, occipital nerve block treatments, and dental splints for headache) iv. Use of opioids or barbiturates for more than 2 days/month.

Note: participants are permitted to take one concomitant migraine preventative treatment (not listed above); however, the dose of this medication should be stable for ≥3 months before start of the screening eDiary.

• Known history of treatment failure to more than four medications prescribed for the prevention of migraine (two of which have different mechanisms of action) or known history of treatment failure to botulinum toxin prescribed for the prevention of migraine