Study of BOTOX Injections in Prevention of Migraine in Adult Participants With Episodic Migraine

Brief Summary

Migraine is a neurological disease characterized by moderate or severe headache, associated with nausea, vomiting, and/or sensitivity to light and sound (International Classification of Headache Disorders, 2018). Migraine can be further categorized according to the frequency of attacks as episodic migraine (EM) or chronic migraine (CM). This study will assess the effects of BOTOX in preventing migraine in adult participants with EM.

BOTOX is being developed for the prevention of migraine in adults with episodic migraine (EM). Participants will be enrolled in 3 different treatment groups. There is 1 in 3 chance that participants will be assigned to receive placebo. Approximately 777 adult participants with EM will be enrolled in approximately 125 sites across the world.

Participants will receive intramuscular injections (injected into the muscle) of BOTOX or Placebo on Day 1 and Week 12. Eligible participants will receive BOTOX on Week 24 and Week 36.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Brief Title

Categories

Headaches & Migraine

Brain, Spinal Cord & Nervous System

Alzheimer's

Brain, Spine & Nerve Cancers

Cancer

Completion Date

2024-11-06

Completion Date Type

Actual

Conditions

Episodic Migraine

Eligibility Criteria

Inclusion Criteria:

* History of migraine headache disorder meeting International Classification of Headache Disorders (ICHD)-3 diagnostic criteria for migraine with aura or migraine without aura for \>= 12 months.
* Onset of migraine before 50 years of age.
* History of 6 to 14 migraine days/month in each of the 3 months prior to Visit 1.
* Six to 14 migraine/probable migraine days during the 4-week screening/baseline phase.
* Less than 15 headache days/month in each of the 3 months prior to Visit 1 and during the 4-week screening/baseline phase.

Exclusion Criteria:

* Current diagnosis of chronic migraine according to ICHD-3.
* History or current diagnosis of migraine with brainstem aura, retinal migraine, complications of migraine, chronic tension-type headache, trigeminal autonomic cephalalgias, hypnic headache, hemicrania continua, or new daily persistent headache.
* History of headache attributed to another disorder (e.g., cervical dystonia, craniotomy, head/neck trauma) with exception that medication overuse headache per ICHD-3 criteria is allowed.
* History of inadequate response to \> 4 prophylactic treatment for migraine, 2 of which have different mechanisms of action.
* Female who is pregnant, breastfeeding, or considering becoming pregnant during the study or within 90 days after the last dose of study drug.

Inclusion Criteria

Inclusion Criteria:

* History of migraine headache disorder meeting International Classification of Headache Disorders (ICHD)-3 diagnostic criteria for migraine with aura or migraine without aura for \>= 12 months.
* Onset of migraine before 50 years of age.
* History of 6 to 14 migraine days/month in each of the 3 months prior to Visit 1.
* Six to 14 migraine/probable migraine days during the 4-week screening/baseline phase.
* Less than 15 headache days/month in each of the 3 months prior to Visit 1 and during the 4-week screening/baseline phase.

Gender

All

Gender Based

false

Keywords

Migraine

Episodic Migraine

BOTOX

Botulinum Toxin Type A

Healthy Volunteers

No

Last Update Post Date

Tue, 12/09/2025 - 12:00

Last Update Post Date Type

Estimated

Last Update Submit Date

Mon, 11/24/2025 - 12:00

Maximum Age

65 Years

Minimum Age

18 Years

NCT Id

NCT05028569

Org Class

Industry

Org Full Name

AbbVie

Org Study Id

M21-307

Overall Status

Terminated

Phases

Phase 3

Primary Completion Date

Wed, 11/06/2024 - 12:00

Primary Completion Date Type

Actual

Official Title

Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study of BOTOX (Botulinum Toxin Type A) for the Prevention of Migraine in Subjects With Episodic Migraine

Primary Outcomes

Outcome Description

The frequency of monthly migraine days across Months 5 and 6 is calculated by taking the 2-month average of monthly migraine days over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. Negative changes from Baseline indicate improvement.

Outcome Measure

Change From Baseline in the Frequency of Monthly Migraine Days Across Months 5 and 6

Outcome Time Frame

Baseline, Months 5-6

Outcome Description

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

Outcome Measure

Number of Participants With Treatment-Emergent Adverse Events (AEs)

Outcome Time Frame

Double-Blind Phase (Week 0-24); Open-Label Phase (Week 24-48)

Secondary Ids

Secondary Id

2021-001979-16

Secondary Outcomes

Outcome Description

The frequency of monthly headache days across Months 5 and 6 is calculated by taking the 2-month average of monthly headache days over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. Negative changes from Baseline indicate improvement.

Outcome Time Frame

Baseline, Months 5-6

Outcome Measure

Change From Baseline in the Frequency of Monthly Headache Days Across Months 5 and 6

Outcome Description

The frequency of monthly migraine days across Months 5 and 6 is calculated by taking the 2-month average of monthly migraine days over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. The responder status of 50% reduction from Baseline is defined as a participant with at least a 50% reduction from Baseline in the 2-month average of monthly migraine days over Months 5 and 6.

Outcome Time Frame

Baseline, Months 5-6

Outcome Measure

Percentage of Participants With ≥ 50% Reduction From Baseline in the Frequency of Monthly Migraine Days Across Months 5 and 6

Outcome Description

Monthly acute headache medication days across Months 5 and 6 is calculated by taking the 2-month average of monthly acute headache medication days over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. Negative changes from Baseline indicate improvement.

Outcome Time Frame

Baseline, Months 5-6

Outcome Measure

Change From Baseline in the Frequency of Monthly Acute Headache Medication Days Across Months 5 and 6

Outcome Description

The MSQ v2.1 is a 14-item questionnaire designed to measure health-related quality of life impairments attributed to migraine over the past 4 weeks. It is divided into 3 domains, and the Role Function Restrictive (RFR) assesses how migraines limit one's daily social and work-related activities using a 6-point scale ranging from "none of the time" to "all of the time". Raw dimension scores are computed as a sum of item responses and rescaled to a 0 to 100 scale, where higher scores indicate better quality of life. Positive changes from Baseline indicate improvement.

Outcome Time Frame

Baseline, Month 6

Outcome Measure

Change From Baseline in Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) Role Function - Restrictive (RFR) Domain Score At Month 6

Outcome Description

AIM-D Physical Impairment Domain score is calculated based on the summation of AIM-D items 6-9. Participants answer each question based on the level of difficulty experienced in the 24 hours prior, with "during your headache" indicated for when they reported a headache, using a 6-point rating scale ranging from "not difficult at all" to "extremely difficult". The raw daily score is transformed to a 0-100 scale, and the monthly score is calculated using the average daily scores, where a higher score indicates worse physical impairment. AIM-D Physical Impairment domain score across Months 5 and 6 is calculated by taking the 2-month average of AIM-D Physical Impairment domain scores over Months 5 and 6. Month 5 and Month 6 are the 28-day daily diary periods ending with Days 56 and Days 84 after the second study treatment intervention day with BOTOX or placebo injections, respectively. Negative changes from Baseline indicate improvement.

Outcome Time Frame

Baseline, Months 5-6

Outcome Measure

Change From Baseline in the Activity Impairment in Migraine - Diary (AIM-D) Physical Impairment Domain Score Across Months 5 and 6

Outcome Description

The HIT-6 is a 6-item assessment used to measure the impact headaches have on a participant's ability to function on the job, at school, at home and in social situations. It assesses the effect that headaches have on normal daily life and the subject's ability to function. Responses are based on frequency using a 5-point scale ranging from "never" to "always." The HIT-6 total score, which ranges from 36 to 78, is the sum of the responses, each of which is assigned a score ranging from 6 points (never) to 13 points (always). The Total 6-item Headache Impact Test (HIT-6) score across Months 5 and 6 is calculated by taking the 2-month average of total 6-item Headache Impact Test (HIT-6) scores over Months 5 and 6. Negative changes from Baseline in the HIT-6 score indicate improvement.

Outcome Time Frame

Baseline, Months 5-6

Outcome Measure

Change From Baseline in the Total 6-item Headache Impact Test (HIT-6) Score Across Months 5 and 6