Episodic Migraine
Conditions
Brief summary
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).
Interventions
BIOLOGICALBotulinum toxin type A
Dose "A" U /Injection (U/I) , Intramuscular (IM) on every 12 weeks during a period of 36 weeks with a total of 4 injections.
OTHERPlacebo
"0" U/I, IM on Day 1 and Week 12 with a total of 2 injections.
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in monthly migraine days (MMD) | Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24) | The monthly migraine days (MMD) is assessed by a daily eDiary, completed by the participant, to evaluate the efficacy of Dysport® compared to placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in MHD of moderate or severe intensity of ≥75% | Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24) | The intensity of monthly headache days (MHD) is assessed by a daily eDiary. |
| Cumulative number of MHD of moderate to severe intensity | From Day 1 to Week 24 | The cumulative number of monthly headache days (MHD) is assessed by a daily eDiary. |
| Change from baseline in the number of days per month of acute migraine medication intake | Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24) | The acute migraine medication intake will be recorded in the daily eDiary Acute migraine medication is defined as triptan, ergotamine, gepant, or ditan |
| Use of acute migraine medication (yes or no) | Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24) | The use of acute migraine medication will be recorded in the daily eDiary. |
| Patient's Global Impression of Change (PGIC) score | At Week 12 and Week 24 | 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) |
| PGIC score of grade ≥1 and ≥2 | At Week 12 and Week 24 | 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) |
| Change from baseline in role function restrictive (RFR) domain of Migraine Specific Quality of Life Questionnaire (MSQ) | At Week 12 and Week 24 | The MSQ will be assessed by a questionnaire (Scores range from 0-100, higher scores indicate a better quality of life) |
| Change from baseline in role function-preventive (RFP) domain of MSQ Questionnaire | At Week 12 and Week 24 | The MSQ will be assessed by a questionnaire (Scores range from 0-100, higher scores indicate a better quality of life) |
| Change from baseline in emotional function (EF) domain of MSQ Questionnaire | At Week 12 and Week 24 | The MSQ will be assessed by a questionnaire (Scores range from 0-100, higher scores indicate a better quality of life) |
| Change from baseline in total MSQ score | At Week 12 and Week 24 | The MSQ will be assessed by a questionnaire (Scores range from 0-100, higher scores indicate a better quality of life) |
| Change in MSQ score to the minimally important change (MIC) | At Week 12 and Week 24 | The MSQ will be assessed by a questionnaire (Scores range from 0-100, higher scores indicate a better quality of life) |
| Change from baseline in total 6-item Headache Impact Test (HIT-6) score | At Week 12 and Week 24 | The HIT-6 will be assessed by a questionnaire (scores range from 36-78 and higher scores indicate a greater impact of headache on subject's life) |
| Change in total 6-item Headache Impact Text (HIT-6) score to the MIC thresholds | At Week 12 and Week 24 | The HIT-6 will be assessed by a questionnaire (scores range from 36-78 and higher scores indicate a greater impact of headache on subject's life) |
| Change from baseline in Short Form 12 (SF-12) Questionnaire score | At Week 12 and Week 24 | The SF-12 will be assessed by a questionnaire (scores range from 0-100, with higher scores indicating better functioning) |
| Change from baseline to Chronic migraine status | At Week 24 (Week 21-24) | Transition to Chronic migraine status will be assessed by the daily eDiary and defined as number of participants with ≥15 MHD and ≥8 MMD |
| Time to onset of effect | From first time point post randomisation to Week 24 | Time to onset of effect is defined as the first time point post randomisation where MMD is reduced from baseline ≥50% |
| Incidence of Treatment emergent adverse event (TEAEs) | Up to Week 24 | An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
| Percentage of Participants with clinically significant changes in vital signs | From baseline up to Week 24 | Percentage of participants with clinically significant changes in vital signs will be reported. The clinical significance will be graded by the investigator. |
| Change from baseline in MHD of moderate or severe intensity of ≥50% | Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24) | The intensity of monthly headache days (MHD) is assessed by a daily eDiary. |
| Change from baseline in MMD of ≥50% | Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24) | The monthly migraine days (MMD) is assessed by a daily eDiary. |
| Change from baseline in MMD of ≥75% | Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24) | The monthly migraine days (MMD) is assessed by a daily eDiary. |
| Cumulative number of MMD | From Day 1 to Week 24 | The cumulative number of monthly migraine days (MMD) is assessed by a daily eDiary. |
| Change from baseline in MMD of moderate or severe intensity | Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24) | The intensity of MMD is assessed by a daily eDiary. |
| Change from baseline in the number of MMD over the last 12 weeks prior to Week 24 | Weeks 13-24 | The monthly migraine days (MMD) is assessed by a daily eDiary. |
| Change from baseline in monthly headache days (MHD) of moderate or severe intensity | Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24) | The intensity of monthly headache days (MHD) is assessed by a daily eDiary. |
| Percentage of participants with clinically significant laboratory parameters (blood chemistry, haematology) | From baseline up to Week 24 | Percentage of participants with clinically significant change in laboratory parameters (blood chemistry, hematology and coagulation) will be reported. The clinical significance will graded by the investigator. |
| Treatment-emergence of suicidal ideation/suicidal behaviour | From baseline up to Week 24 | It will be assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire that consists of 4 subscales: 1. Ideation severity subscale: questions answered yes/no, severity of ideation scored 1-5 with 5 being most severe 2. Intensity of ideation subscale : scores range from 2-25 with higher scores indicating more severe intensity of ideation. 3. Suicide behaviour subscale:4 types of suicidal behaviours are scored yes/no 4. Behaviour Lethality subscale: actual lethality/medical damage scores 0-5, with 5 being most severe (death) and potential lethality scores 0-2 with 2 being more potentially lethal. |
| Percentage of participants with binding antibodies to Dysport® | At Week 24 | Presence of binding antibodies will be assessed using a validated method of electrochemiluminescence assay (ECLA). |
| Headache medication overuser (yes, no) | Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24) | 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) |
| Percentage of participants with neutralising antibodies to Dysport® | At Week 24 | It will be performed only for confirmed positive samples with ECLA (confirmation of the presence of binding antibodies). Presence of neutralizing antibodies will be assessed using a validated cell-based assay (CBA). |
Countries
Canada, Czechia, France, Georgia, Germany, Poland, Spain, United States
Contacts
STUDY_DIRECTORIpsen Medical Director
Ipsen
Outcome results
None listed