A Study to Evaluate the Effectiveness and Safety of Dysport® for the Prevention of Chronic Migraine in Adults (C-BEOND)

• ClinicalTrials.gov Identifier: NCT06047444
• Recruitment Status: Recruiting
• First Posted: September 21, 2023
• Last Update Posted: April 29, 2024
• Sponsor: Ipsen
• Information provided by (Responsible Party): Ipsen

Tracking Information

• First Submitted Date: September 14, 2023
• First Posted Date: September 21, 2023
• Last Update Posted Date: April 29, 2024
• Actual Study Start Date: October 12, 2023
• Estimated Primary Completion Date: June 22, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 14, 2023)

Change from baseline in monthly migraine days (MMD) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 27, 2023)

• Change from baseline in MMD of ≥50% [ Time Frame: 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% [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 monthly headache days (MHD) of moderate or severe intensity [ Time Frame: 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 MHD of moderate or severe intensity of ≥50% [ Time Frame: 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 MHD of moderate or severe intensity of ≥75% [ Time Frame: 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 or severe intensity [ Time Frame: 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 [ Time Frame: 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
• Headache medication overuser (yes, no) [ Time Frame: 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)
• Use of acute migraine medication (yes or no) [ Time Frame: 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 [ Time Frame: 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)
• Change from baseline of ≥1 and ≥2 grades in PGIC score [ Time Frame: 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)
• Change from baseline in role function restrictive domain of Migraine Specific Quality of Life (MSQ) Questionnaire [ Time Frame: 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)
• Change from baseline in total MSQ score [ Time Frame: 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)
• Change in MSQ score to the minimally important difference/change (MID/MIC) [ Time Frame: 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)
• Change from baseline in total 6-item Headache Impact Test (HIT-6) score [ Time Frame: 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 HIT-6 score to MID/MIC [ Time Frame: 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)
• Change from baseline in Short Form 12 (SF-12) Questionnaire score [ Time Frame: 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)
• Chronic migraine status [ Time Frame: 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
• Time to onset of effect [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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.
• Percentage of participants with clinically significant laboratory parameters (blood chemistry, haematology) [ Time Frame: 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 [ Time Frame: 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® [ Time Frame: 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.
• Percentage of participants with neutralising antibodies to Dysport® [ Time Frame: 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

Original Secondary Outcome Measures (submitted: September 14, 2023)

• Reduction from baseline in MMD of ≥50% [ Time Frame: 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.
• Reduction from baseline in MMD of ≥75% [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 monthly headache days (MHD) of moderate or severe intensity [ Time Frame: 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 MHD of moderate or severe intensity of ≥50% [ Time Frame: 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 MHD of moderate or severe intensity of ≥75% [ Time Frame: 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 or severe intensity [ Time Frame: 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 [ Time Frame: 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
• Headache medication overuser (yes, no) [ Time Frame: 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)
• Use of acute migraine medication (yes or no) [ Time Frame: 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 [ Time Frame: At Week 24 ]
  The PGIC will be assessed by a questionnaire
• Improvement from baseline of ≥1 and ≥2 grades in PGIC score [ Time Frame: At Week 24 ]
  The PGIC will be assessed by a questionnaire
• Change from baseline in role function restrictive domain of Migraine Specific Quality of Life (MSQ) Questionnaire [ Time Frame: At Week 24 ]
  The MSQ will be assessed by a questionnaire
• Change from baseline in total MSQ score [ Time Frame: At Week 24 ]
  The MSQ will be assessed by a questionnaire
• Improvement in MSQ score to the minimally important difference/change (MID/MIC) [ Time Frame: At Week 24 ]
  The MSQ will be assessed by a questionnaire
• Change from baseline in HIT-6 score to MID/MIC [ Time Frame: At Week 24 ]
  The HIT-6 will be assessed by a questionnaire
• Improvement in total 6-item Headache Impact Text (HIT-6) score to MID/MIC [ Time Frame: At Week 24 ]
  The HIT-6 will be assessed by a questionnaire
• Change from baseline in Short Form 12 (SF-12) Questionnaire score [ Time Frame: At Week 24 ]
  The SF-12 will be assessed by a questionnaire
• Change form baseline on Chronic migraine status [ Time Frame: 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
• Time to onset of effect [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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.
• Percentage of participants with clinically significant laboratory parameters (blood chemistry, haematology) [ Time Frame: 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 [ Time Frame: From baseline, at Week 24 ]
  It will be assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire
• Percentage of participants with Binding antibodies to Dysport® [ Time Frame: 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.
• Percentage of participants with neutralising antibodies to Dysport® [ Time Frame: 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Effectiveness and Safety of Dysport® for the Prevention of Chronic Migraine in Adults
• Official Title: 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

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 chronic 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.

Chronic migraine is defined as having at least 15 days of headache a month with at least 8 of those days being migraine headache days.

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 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).

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Chronic Migraine

Intervention

• 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.
  Other Name: Dysport®
• Biological: Botulinum toxin type A
  Dose "B" U/I, IM on every 12 weeks during a period of 36 weeks with a total of 4 injections.
  Other Name: Dysport®
• Other: Placebo
  "0" U/I, IM on Day 1 and Week 12 with a total of 2 injections.
• Biological: Botulinum toxin type A
  Dose "A" U/I, IM at Week 24 and Week 36 with a total of 2 injections.
  Other Name: Dysport®
• Biological: Botulinum toxin type A
  Dose "B" U/I, IM at Week 24 and Week 36 with a total of 2 injections.
  Other Name: Dysport®

Study Arms

• Experimental: 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)

  Intervention: Biological: Botulinum toxin type A
• Experimental: 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)

  Intervention: Biological: Botulinum toxin type A
• Placebo Comparator: 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)

  Interventions:

  • Other: Placebo
  • Biological: Botulinum toxin type A
• Placebo Comparator: 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).

  Interventions:

  • Other: Placebo
  • Biological: Botulinum toxin type A

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 14, 2023): 720
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 21, 2026
• Estimated Primary Completion Date: June 22, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Ipsen Clinical Study Enquiries; See e mail; clinical.trials@ipsen.com

• Listed Location Countries: Canada, Czechia, Georgia, Germany, Italy, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT06047444
• Other Study ID Numbers: CLIN-52120-463
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants. Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.
• Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
• URL: https://vivli.org/members/ourmembers/

• Current Responsible Party: Ipsen
• Original Responsible Party: Same as current
• Current Study Sponsor: Ipsen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Ipsen Medical Director; Ipsen

• PRS Account: Ipsen
• Verification Date: April 2024