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 Chronic Migraine in Adult Participants

ClinicalTrials.gov processed this data on June 28, 2024. Link to the current ClinicalTrials.gov record.

Recruitment Status

RECRUITING (See Contacts and Locations)
Verified June 2024 by Ipsen

Sponsor

Ipsen

Information Provided by (Responsible Party)

Ipsen

Clinicaltrials.gov Identifier

NCT06047444
Other Study ID Numbers: CLIN-52120-463
First Submitted: September 14, 2023
First Posted: September 21, 2023
Last Update Posted: July 1, 2024
Last Verified: June 2024
History of Changes

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Study Description

Not Provided
Condition or Disease Intervention/Treatment
  • Chronic Migraine
  • Biological: Botulinum toxin type A
  • Biological: Botulinum toxin type A
  • Other: Placebo
  • Biological: Botulinum toxin type A
  • Biological: Botulinum toxin type A

Study Design

Study TypeInterventional
Anticipated Enrollment720 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingDouble
Primary PurposePrevention
Official TitleA 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 Chronic Migraine in Adult Participants
Study Start DateOctober 12, 2023
Anticipated Primary Completion DateJune 22, 2026
Anticipated Study Completion DateDecember 21, 2026

Groups and Cohorts

Group/ CohortIntervention/ Treatment
  • Dysport® dose "A"
    • Participant will receive four treatment cycles, each separated by an interval of 12 weeks.

      Double-blind placebo-controlled (DBPC) Phase: Dysport® dose "A" administered intramuscularly on Day 1 and Week 12.

      Extension Phase: Dysport® dose "A" administered intramuscularly at Week 24 and Week 36 (final follow-up at Week 48)
  • Biological: Botulinum toxin type A
    • Dose "A" Unit/Injection (U/I), Intramuscular (IM) on every 12 weeks during a period of 36 weeks with a total of 4 injections.
  • Dysport® dose "B"
    • Participant will receive four treatment cycles, each separated by an interval of 12 weeks.

      DBPC Phase: Dysport® dose "B" administered intramuscularly on Day 1 and Week 12.

      Extension Phase: Dysport® dose "B" administered intramuscularly at Week 24 and Week 36 (final follow-up at Week 48)
  • Biological: Botulinum toxin type A
    • Dose "A" Unit/Injection (U/I), Intramuscular (IM) on every 12 weeks during a period of 36 weeks with a total of 4 injections.
  • Placebo - Dysport dose "A"
    • Participant will receive four treatment cycles, each separated by an interval of 12 weeks.

      DBPC Phase: Placebo dose "A" administered intramuscularly on Day 1 and Week 12

      Extension Phase: Dysport® dose "A" administered intramuscularly at Week 24 and Week 36 (final follow-up at Week 48)
  • Other: Placebo
    • Biological: Botulinum toxin type A
      • Dose "A" Unit/Injection (U/I), Intramuscular (IM) on every 12 weeks during a period of 36 weeks with a total of 4 injections.
    • Placebo - Dysport dose "B"
      • Participant will receive four treatment cycles, each separated by an interval of 12 weeks.

        DBPC Phase: Placebo dose "B" administered intramuscularly on Day 1 and Week 12.

        Extension Phase: Dysport® dose "B" administered intramuscularly at Week 24 and Week 36 (final follow-up at Week 48).
    • Other: Placebo
      • Biological: Botulinum toxin type A
        • Dose "A" Unit/Injection (U/I), Intramuscular (IM) on every 12 weeks during a period of 36 weeks with a total of 4 injections.

      Outcome Measures

      Primary Outcome Measures

      1. 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 eDiary, completed every day by the participant, to evaluate the efficacy of Dysport® compared to placebo.

      Secondary Outcome Measures

      1. 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.
      2. 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.
      3. Cumulative number of MMD [From Day 1 to Week 24]
        The cumulative number of monthly migraine days (MMD) is assessed by a daily eDiary.
      4. 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.
      5. 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.
      6. 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.
      7. 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.
      8. Cumulative number of MHD of moderate or severe intensity [From Day 1 to Week 24]
        The cumulative number of monthly headache days (MHD) is assessed by a daily eDiary.
      9. 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
      10. 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)
      11. 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.
      12. Patient's Global Impression of Change (PGIC) score [At Weeek 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)
      13. Change from baseline of ≥1 and ≥2 grades in PGIC score [At Weeek 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)
      14. Change from baseline in role function restrictive domain of Migraine Specific Quality of Life (MSQ) Questionnaire [At Weeek 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)
      15. Change from baseline in total MSQ score [At Weeek 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)
      16. Change in MSQ score to the minimally important difference/change (MID/MIC) [At Weeek 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)
      17. 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)
      18. Change from baseline in HIT-6 score to MID/MIC [At Weeek 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)
      19. Change from baseline in Short Form 12 (SF-12) Questionnaire score [At Weeek 12 and Week 24]
        The SF-12 will be assessed by a questionnaire (scores range from 0-100, with higher scores indicating better functioning)
      20. Chronic migraine status [At Week 24 (Week 21-24)]
        Chronic migraine status will be assessed by the daily eDiary and defined as number of participants with ≥15 MHD and ≥8 MMD
      21. 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%
      22. 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.
      23. 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.
      24. 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.
      25. 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:

        Ideation severity subscale: questions answered yes/no, severity of ideation scored 1-5 with 5 being most severe

        Intensity of ideation subscale : scores range from 2-25 with higher scores indicating more severe intensity of ideation.

        Suicide behaviour subscale:4 types of suicidal behaviours are scored yes/no

        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.
      26. Percentage of participants with Binding antibodies to Dysport® [At Week 24]
        It will be assessed by collecting blood samples at baseline and Week 24. The determination of putative antibodies against BoNT-A will be evaluated using a validated method of electrochemiluminescence assays (ECLA) for the presence of binding antibodies to BoNT-A.
      27. Percentage of participants with neutralising antibodies to Dysport® [At Week 24]
        It will be performed only with confirmed positive samples in ECLA (confirmation of presence of binding antibodies) . The characterization of antibodies against BoNT-A will be evaluated using a validated method of cell-based assays (CBA) for the presence of neutralising antibodies to BoNT-A

      Eligibility Criteria

      Ages Eligible for Study 18 Years and Older (Adult, Older Adult)
      Sexes Eligible for Study All
      Accepts Healthy Volunteers No
      Inclusion Criteria
      • Participant 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 chronic migraine 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) ≥15 and baseline number of monthly migraine days (MMD) of ≥8, 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
      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 completion 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)ii. Cannabidiol 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

      Contacts and Locations

      Sponsors and Collaborators Ipsen
      Locations
      • 840024 | Birmingham, Alabama, United States, 35205
      • 840018 | Phoenix, Arizona, United States, 85044
      • 840034 | Scottsdale, Arizona, United States, 85251
      • 840027 | Tempe, Arizona, United States, 85281
      • 840030 | Fullerton, California, United States, 92835
      • 840039 | Fullerton, California, United States, 92835
      • 840037 | Los Angeles, California, United States, 90067
      • 840010 | Orange, California, United States, 92868
      • 840011 | Palo Alto, California, United States, 94304
      • 840029 | Aurora, Colorado, United States, 80045
      • 840023 | Aventura, Florida, United States, 33180
      • 840004 | Hialeah, Florida, United States, 33012
      • 840013 | Hollywood, Florida, United States, 33024
      • 840042 | Miami, Florida, United States, 33136
      • 840032 | Tampa, Florida, United States, 33614
      • 840040 | Tampa, Florida, United States, 33620
      • 840052 | Winter Park, Florida, United States, 32789
      • 840038 | Savannah, Georgia, United States, 31406
      • 840046 | Chicago, Illinois, United States, 60657
      • 840035 | Riverwoods, Illinois, United States, 60015
      • 840021 | Fort Wayne, Indiana, United States, 46804
      • 840051 | Boston, Massachusetts, United States, 02131
      • 840031 | Burnsville, Minnesota, United States, 55337
      • 840017 | Chesterfield, Missouri, United States, 63005
      • 840049 | Papillion, Nebraska, United States, 68046
      • 840043 | Las Vegas, Nevada, United States, 89128
      • 840019 | Amherst, New York, United States, 14226
      • 840001 | Brooklyn, New York, United States, 11235
      • 840014 | Poughkeepsie, New York, United States, 12601
      • 840009 | Rochester, New York, United States, 14609
      • 840005 | Hendersonville, North Carolina, United States, 28792
      • 840026 | New Albany, Ohio, United States, 43054
      • 840044 | Portland, Oregon, United States, 97225
      • 840022 | Philadelphia, Pennsylvania, United States, 19107
      • 840008 | Cordova, Tennessee, United States, 38018
      • 840025 | Frisco, Texas, United States, 75034
      • 840012 | Houston, Texas, United States, 77074
      • 840007 | Plano, Texas, United States, 75093
      • 840036 | Salt Lake City, Utah, United States, 84109
      • 840015 | West Valley City, Utah, United States, 84119
      • 840020 | Columbia, Washington, United States, 20010
      • 124007 | Halifax, Canada, B3S 1N2
      • 124005 | Montréal, Canada,
      • 124004 | Red Deer, Canada,
      • 124003 | Sarnia, Canada, N7T 4X3
      • 203007 | Brno, Czechia,
      • 203008 | Brno, Czechia,
      • 203005 | Jihlava, Czechia,
      • 203010 | Ostrava - Poruba, Czechia,
      • 203004 | Praha 4, Czechia,
      • 203011 | Praha 5, Czechia,
      • 203003 | Praha 8, Czechia,
      • 203006 | Praha, Czechia,
      • 268002 | Batumi, Georgia, 6010
      • 268004 | Tbilisi, Georgia, 0112
      • 268003 | Tbilisi, Georgia, 0114
      • 268006 | Tbilisi, Georgia, 0114
      • 268005 | Tbilisi, Georgia, 0179
      • 268001 | Tbilisi, Georgia, 0186
      • 276002 | Berlin, Germany,
      • 276007 | Berlin, Germany,
      • 276003 | Greifswald, Germany,
      • 276004 | Haag In Oberbayern, Germany,
      • 276006 | Kassel, Germany,
      • 276001 | München, Germany,
      • 380006 | Bologna, Italy,
      • 380005 | Napoli, Italy,
      • 380001 | Pavia, Italy,
      • 380003 | Pozzilli, Italy,
      • 380002 | Roma, Italy,
      • 380004 | Roma, Italy,
      • 616004 | Bydgoszcz, Poland,
      • 616001 | Gdynia, Poland,
      • 616006 | Katowice, Poland,
      • 616003 | Kraków, Poland,
      • 616005 | Kraków, Poland,
      • 616007 | Kraków, Poland,
      • 616002 | Lublin, Poland,
      • 616008 | Oswiecim, Poland,
      • 724009 | Córdoba, Spain,
      • 724002 | Madrid, Spain,
      • 724006 | Madrid, Spain,
      • 724001 | Málaga, Spain,
      • 724010 | Sevilla, Spain,
      • 724003 | Valencia, Spain,
      • 724008 | Valencia, Spain,
      • 724004 | Zaragoza, Spain,
      • 826002 | Brighton, United Kingdom,
      • 826001 | Brixton, United Kingdom,
      Investigators

        More Information

        Additional Relevant MeSH Terms

        • Migraine Disorders
        • Headache Disorders, Primary
        • Headache Disorders
        • Brain Diseases
        • Central Nervous System Diseases
        • Nervous System Diseases