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

Primary Purpose

Chronic Migraine

Status

Recruiting

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Dysport®

Placebo

Dysport®

About this trial

This is an interventional prevention trial for Chronic Migraine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Neurology Center of North Orange County
Visionary Investigators Network (VIN)
Robbins Headache Clinic
MD Fort Wayne Neurological Center
Blue Sky MD
OrthoNeuro
Research Your HealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

Dysport® dose "A"

Dysport® dose "B"

Placebo - Dysport dose "A"

Placebo - Dysport dose "B"

Arm Description

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)

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)

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)

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).

Outcomes

Primary Outcome Measures

Change from baseline in monthly migraine days (MMD)

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

Change from baseline in MMD of ≥50%

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

Change from baseline in MMD of ≥75%

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

Cumulative number of MMD

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

Change from baseline in MMD of moderate or severe intensity

The intensity of MMD is assessed by a daily eDiary.

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.

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.

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.

Cumulative number of MHD of moderate or severe intensity

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

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)

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)

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

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)

Change from baseline of ≥1 and ≥2 grades in 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)

Change from baseline in role function restrictive domain of Migraine Specific Quality of Life (MSQ) Questionnaire

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

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)

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

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

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

The SF-12 will be assessed by a questionnaire (scores range from 0-100, with higher scores indicating better functioning)

Chronic migraine status

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 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)

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

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)

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

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.

Percentage of participants with Binding antibodies to Dysport®

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®

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

Full Information

NCT ID

NCT06047444

First Posted

September 14, 2023

Last Updated

October 17, 2023

Sponsor

Ipsen

1. Study Identification

Unique Protocol Identification Number

NCT06047444

Brief Title

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

Acronym

C-BEOND

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 12, 2023 (Actual)

Primary Completion Date

June 1, 2025 (Anticipated)

Study Completion Date

January 26, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ipsen

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Migraine

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

720 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Dysport® dose "A"

Arm Type

Experimental

Arm Description

Arm Title

Dysport® dose "B"

Arm Type

Experimental

Arm Description

Arm Title

Placebo - Dysport dose "A"

Arm Type

Placebo Comparator

Arm Description

Arm Title

Placebo - Dysport dose "B"

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

Dysport®

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Dysport®

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Dysport®

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Dysport®

Intervention Description

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

Primary Outcome Measure Information:

Title

Change from baseline in monthly migraine days (MMD)

Description

The monthly migraine days (MMD) is assessed by eDiary, completed every day 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 Outcome Measure Information:

Title

Change from baseline in MMD of ≥50%

Description

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)

Title

Change from baseline in MMD of ≥75%

Description

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)

Title

Cumulative number of MMD

Description

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

Time Frame

From Day 1 to Week 24

Title

Change from baseline in MMD of moderate or severe intensity

Description

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)

Title

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

Description

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)

Title

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

Description

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)

Title

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

Description

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)

Title

Cumulative number of MHD of moderate or severe intensity

Description

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

Time Frame

From Day 1 to Week 24

Title

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

Description

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)

Title

Headache medication overuser (yes, no)

Description

Time Frame

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

Title

Use of acute migraine medication (yes or no)

Description

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)

Title

Patient's Global Impression of Change (PGIC) score

Description

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)

Time Frame

At Weeek 12 and Week 24

Title

Change from baseline of ≥1 and ≥2 grades in PGIC score

Description

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)

Time Frame

At Weeek 12 and Week 24

Title

Change from baseline in role function restrictive domain of Migraine Specific Quality of Life (MSQ) Questionnaire

Description

The MSQ will be assessed by a questionnaire (Scores range from 0-100, higher scores indicate a better quality of life)

Time Frame

At Weeek 12 and Week 24

Title

Change from baseline in total MSQ score

Description

The MSQ will be assessed by a questionnaire (Scores range from 0-100, higher scores indicate a better quality of life)

Time Frame

At Weeek 12 and Week 24

Title

Change in MSQ score to the minimally important difference/change (MID/MIC)

Description

The MSQ will be assessed by a questionnaire (Scores range from 0-100, higher scores indicate a better quality of life)

Time Frame

At Weeek 12 and Week 24

Title

Change from baseline in total 6-item Headache Impact Test (HIT-6) score

Description

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)

Time Frame

At Week 12 and Week 24

Title

Change from baseline in HIT-6 score to MID/MIC

Description

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)

Time Frame

At Weeek 12 and Week 24

Title

Change from baseline in Short Form 12 (SF-12) Questionnaire score

Description

The SF-12 will be assessed by a questionnaire (scores range from 0-100, with higher scores indicating better functioning)

Time Frame

At Weeek 12 and Week 24

Title

Chronic migraine status

Description

Chronic migraine status will be assessed by the daily eDiary and defined as number of participants with ≥15 MHD and ≥8 MMD

Time Frame

At Week 24 (Week 21-24)

Title

Time to onset of effect

Description

Time to onset of effect is defined as the first time point post randomisation where MMD is reduced from baseline ≥50%

Time Frame

From first time point post randomisation to Week 24

Title

Incidence of Treatment emergent adverse event (TEAEs)

Description

Time Frame

Up to Week 24

Title

Percentage of Participants with clinically significant changes in vital signs

Description

Percentage of participants with clinically significant changes in vital signs will be reported. The clinical significance will be graded by the investigator.

Time Frame

From baseline up to Week 24

Title

Percentage of participants with clinically significant laboratory parameters (blood chemistry, haematology)

Description

Time Frame

From baseline up to Week 24

Title

Treatment-emergence of suicidal ideation/suicidal behaviour

Description

Time Frame

From baseline up to Week 24

Title

Percentage of participants with Binding antibodies to Dysport®

Description

Time Frame

At Week 24

Title

Percentage of participants with neutralising antibodies to Dysport®

Description

Time Frame

At Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ipsen Clinical Study Enquiries

Phone

See e mail

clinical.trials@ipsen.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ipsen Medical Director

Organizational Affiliation

Ipsen

Official's Role

Study Director

Facility Information:

Facility Name

Neurology Center of North Orange County

City

Fullerton

State/Province

California

ZIP/Postal Code

92835

Country

United States

Individual Site Status

Not yet recruiting

Facility Name

Visionary Investigators Network (VIN)

City

Aventura

State/Province

Florida

ZIP/Postal Code

33180

Country

United States

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Facility Name

Robbins Headache Clinic

City

Riverwoods

State/Province

Illinois

ZIP/Postal Code

60015

Country

United States

Individual Site Status

Not yet recruiting

Facility Name

MD Fort Wayne Neurological Center

City

Fort Wayne

State/Province

Indiana

ZIP/Postal Code

46804

Country

United States

Individual Site Status

Active, not recruiting

Facility Name

Blue Sky MD

City

Hendersonville

State/Province

North Carolina

ZIP/Postal Code

28792

Country

United States

Individual Site Status

Active, not recruiting

Facility Name

OrthoNeuro

City

New Albany

State/Province

Ohio

ZIP/Postal Code

43054

Country

United States

Individual Site Status

Active, not recruiting

Facility Name

Research Your Health

City

Plano

State/Province

Texas

ZIP/Postal Code

75093

Country

United States

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing Access Criteria

Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).

IPD Sharing URL

https://vivli.org/members/ourmembers/

Learn more about this trial

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

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