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

Phase 3Active Not RecruitingNCT06047457

Ipsen751 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Interventions

Botulinum toxin type ABIOLOGICAL

Dose "A" U /Injection (U/I) , Intramuscular (IM) on every 12 weeks during a period of 36 weeks with a total of 4 injections.

Botulinum toxin type ABIOLOGICAL

Dose "B" U/I, IM on every 12 weeks during a period of 36 weeks with a total of 4 injections.

PlaceboOTHER

"0" U/I, IM on Day 1 and Week 12 with a total of 2 injections.

Botulinum toxin type ABIOLOGICAL

Dose "A" U/I, IM on Week 24 and Week 36 with a total of 2 injections.

Botulinum toxin type ABIOLOGICAL

Dose "B" U/I, IM on Week 24 and Week 36 with a total of 2 injections.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (105)

Central Research Associates

Birmingham, Alabama, United States

CCT Research

Phoenix, Arizona, United States

HonorHealth Neurology

Scottsdale, Arizona, United States

Hope Clinical Research, LLC

Canoga Park, California, United States

Axiom Research LLC

Colton, California, United States

Fullerton Neurological Center

Outcomes

Primary Outcomes

Change from baseline in monthly migraine days (MMD)

The monthly migraine days (MMD) is assessed by a daily eDiary, completed by the participant, to evaluate the efficacy of Dysport® compared to placebo.

Time frame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)

Secondary Outcomes

Change from baseline in MMD of ≥50%

The monthly migraine days (MMD) is assessed by a daily eDiary.

Time frame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)

Change from baseline in MMD of ≥75%

The monthly migraine days (MMD) is assessed by a daily eDiary.

Time frame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)

Cumulative number of MMD

The cumulative number of monthly migraine days (MMD) is assessed by a daily eDiary.

Time frame: From Day 1 to Week 24

Change from baseline in MMD of moderate or severe intensity

The intensity of MMD is assessed by a daily eDiary.

Time frame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)

Change from baseline in the number of MMD over the last 12 weeks prior to Week 24

The monthly migraine days (MMD) is assessed by a daily eDiary.

Time frame: Weeks 13-24

Change from baseline in monthly headache days (MHD) of moderate or severe intensity

The intensity of monthly headache days (MHD) is assessed by a daily eDiary.

Time frame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)

Change from baseline in MHD of moderate or severe intensity of ≥50%

The intensity of monthly headache days (MHD) is assessed by a daily eDiary.

Time frame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)

Change from baseline in MHD of moderate or severe intensity of ≥75%

The intensity of monthly headache days (MHD) is assessed by a daily eDiary.

Time frame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)

Cumulative number of MHD of moderate to severe intensity

The cumulative number of monthly headache days (MHD) is assessed by a daily eDiary.

Time frame: From Day 1 to Week 24

Change from baseline in the number of days per month of acute migraine medication intake

The acute migraine medication intake will be recorded in the daily eDiary Acute migraine medication is defined as triptan, ergotamine, gepant, or ditan

Time frame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)

Headache medication overuser (yes, no)

The headache medication overuse will be assessed by a concomitant medication log completed at each visit and acute medication taken to treat acute attack will be recorded in the daily eDiary. The headache medication overuse is defined as a participant with ≥10 days/month if ergotamine, triptan, gepant, ditan, opioid or combination analgesic, or ≥15 days/month if non-opioid analgesic (such as paracetamol, aspirin, NSAID)

Time frame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)

Use of acute migraine medication (yes or no)

The use of acute migraine medication will be recorded in the daily eDiary.

Time frame: Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)

Patient's Global Impression of Change (PGIC) score

The PGIC will be assessed by a questionnaire (7-point scale, score of 1 indicates very much improved and score of 7 indicates very much worse)