Migraine Headache
Conditions
Brief summary
The main purpose of this study is to evaluate whether the study drug known as galcanezumab is safe and effective in the prevention of migraine headaches.
Interventions
DRUGGalcanezumab
Administered SQ
DRUGPlacebo
Administered SQ
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participants with a history of migraine of at least 1 year prior to enrollment. * Migraine onset prior to age 50.
Exclusion criteria
* Current enrollment in, or discontinuation within the last 30 days from, a clinical trial involving any investigational drug or device. * Current use or any prior exposure to any CGRP antibody, any antibody to the CGRP receptor, or antibody to nerve growth factor (NGF). * History of migraine subtypes including hemiplegic migraine, ophthalmoplegic migraine, and basilar-type migraine. * Have a history or presence of other medical illness that indicates a medical problem that would preclude study participation. * Failure to respond to more than two adequately dosed effective migraine prevention treatments. * Evidence of significant active psychiatric disease, in the opinion of the investigator. * Women who are pregnant or nursing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | Baseline, 12 Weeks | The criteria for a migraine headache was adapted from the standard International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both (A and B) required features from the IHS ICHD-3 beta definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥50% Reduction in Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | Week 12 | The criteria for a migraine headache was adapted from the standard International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta definition. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both (A and B) required features from the IHS ICHD-3 beta definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. |
| Mean Change From Baseline in the Number of Days of Medication Use for the Treatment of Migraine Headache in the Last 28-Day Period of the 12-Week Treatment Phase | Baseline, 12 Weeks | A migraine attack was defined as beginning on any day a migraine headache day was recorded and ending when a migraine headache-free day occurred. The criteria was adapted from the standard IHS ICHD-3 beta definition. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both (A and B) required features from the IHS ICHD-3 beta definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with treatment, pooled investigative site, period, and treatment-by-period interaction, baseline and baseline-by-period interaction. |
| Mean Change From Baseline in Number of Headache Hours in the Last 28-Day Period of the 12-Week Treatment Phase | Baseline, 12 Weeks | Number of headache hours calculated as the total number of headache hours in a 28-day period on which a headache occurred. Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with treatment, pooled investigative site, period, and treatment-by-period interaction, baseline and baseline-by-period interaction. |
| Change From Baseline to 12 Week Endpoint in Migraine Specific Quality of Life (MSQL) Questionnaire Total Scores | Baseline, 12 Weeks | MSQL consists of 14 questions across 3 dimensions (role function-restrictive, role function-preventive, and emotional function). All question values range from 1 to 6. Participants rated each item from 1 (none of the time) to 6 (all of the time). Since each item was presented as a negative statement, participant responses were recorded before item scores were calculated. Then, dimension scores were calculated as the sum of the recorded items for that specific dimension. Each dimension score was transformed into a score that ranged from 0 to 100. The transformation formula for the restrictive function = \[(dimension score-7)\*100\]/35, for the preventive function = \[(dimension score-4)\*100\]/20, and for the emotional function = \[(dimension score-3)\*100\]/15. A lower score indicated a poorer quality of life associated with that domain. LS means was determined by Analysis of covariance (ANCOVA) with treatment, pooled investigative site and baseline. |
| Change From Baseline to 12 Week Endpoint in the Headache Impact Test-6™ (HIT-6™) Scores | Baseline, 12 Weeks | The HIT-6 consists of 6 questions to measure the impact of headaches on the participants ability to function on the job, at school, at home and in social situations. A score to each question will be assigned as follows: never - 6, rarely - 8, sometimes - 10, very often - 11, and always - 13. The composite score is calculated as the sum of the scores for all 6 questions, the total score ranges between 36 and 78 with higher total scores reflecting more severe impact of headaches. LS means was determined by ANCOVA with treatment, pooled investigative site and baseline. |
| Mean Change From Baseline in Number of Migraine Attacks in the Last 28-Day Period of the 12-Week Treatment Phase | Baseline, 12 Weeks | A migraine attack was defined as beginning on any day a migraine headache day was recorded and ending when a migraine headache-free day occurred. The criteria was adapted from the standard IHS ICHD-3 beta definition. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both (A and B) required features from the IHS ICHD-3 beta definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. Least Squares (LS) mean was calculated using mixed model repeated measures (MMRM) methodology with treatment, pooled investigative site, period, and treatment-by-period interaction, baseline and baseline-by-period interaction. |
| Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | 12 Weeks | CGRP has been shown to be involved in the pathophysiology of migraine through dilation of cerebral and dural blood vessels, release of inflammatory mediators, and transmission of nociceptive (pain) information from intracranial blood vessels to the nervous system (Villalón and Olesen 2009). In migraineurs, serum concentrations of CGRP are significantly elevated during migraine attacks (Goadsby et al. 1990; Goadsby and Edvinsson 1993). |
| Percentage of Participants Developing Anti-drug Antibodies to Galcanezumab | Baseline through 12 Weeks | The percent of participants with treatment emergent Anti-drug Antibodies (ADA) were assessed at week 1 to 12. A participant was considered to have treatment-emergent Galcanezumab ADA if the participant had at least 1 titer that was treatment-emergent relative to baseline, defined as any of the following: A negative baseline ADA result and a subsequent positive post-baseline ADA result with a titer \>=20; or a positive ADA results and a subsequent positive post-baseline ADA results with a 4-fold or greater increase in titer from the baseline measurement. |
| Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | Baseline through Week 12 | The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The scale includes suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. Some questions are binary responses (yes/no) and some are on a scale of 1 (low severity) to 5 (high severity). Suicidal behavior: a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. |
| Mean Change From Baseline in the Number of Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | Baseline, 12 Weeks | Number of calendar days on which a headache lasts ≥4 hours which includes migraines, probable migraines (PM) and nonmigraines. Criteria for migraine headache (MH) was adapted from standard IHS ICHD-3 beta definition. It is defined as headache with or without aura, of ≥30 min duration, and with both (A and B) required features from IHS ICHD-3 beta definition. Required feature A includes ≥2 of following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of following during headache: nausea and/or vomiting, or photophobia and phonophobia. PM is headache with or without aura, but missing 1 feature needed to fulfill all criteria for MH. LS means were calculated using MMRM with treatment, pooled investigative site, period, and treatment-by-period interaction, baseline and baseline-by-period interaction. |
| Mean Change From Baseline in the Number of Moderate-Severe Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | Baseline, 12 Weeks | Number of calendar days on which headache lasts ≥4 hrs it includes migraines, PM & non-migraines. MH is headache with or without aura, of ≥30 min duration, and with both (A and B) required features from IHS ICHD-3 beta definition. Required feature A includes ≥2 of following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of following during headache: nausea &/or vomiting, or photophobia & phonophobia. PM is headache with or without aura, but missing 1 feature needed to fulfill all criteria for MH. Severity was measured via interactive voice response system questionnaire What was the worst headache pain? For mild press 1. For moderate 2. For severe press 3. LSmean was calculated using MMRM with treatment, pooled investigative site, period, treatment-by-period interaction, baseline and baseline-by-period interaction. |
| Serum Concentration of Galcanezumab | 12 Weeks | Blood serum concentrations of galcanezumab. |
Countries
United States
Participant flow
Recruitment details
Treatment period (0 to 12 weeks), Post-treatment period (12 to 24 weeks)
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo given as SQ injections once every 28 days during a 12 week treatment period. | 137 |
| 5mg Galcanezumab 5mg of galcanezumab given as subcutaneous (SQ) injections once every 28 days during a 12 week treatment period. | 68 |
| 50mg Galcanezumab 50mg of galcanezumab given as SQ injections once every 28 days during a 12 week treatment period. | 68 |
| 120mg Galcanezumab 120mg of galcanezumab given as SQ injections once every 28 days during a 12 week treatment period. | 70 |
| 300mg Galcanezumab 300mg of galcanezumab given as SQ injections once every 28 days during a 12 week treatment period. | 67 |
| Total | 410 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Post-treatment Period | Adverse Event | 0 | 0 | 1 | 0 | 0 |
| Post-treatment Period | Lost to Follow-up | 2 | 2 | 3 | 1 | 0 |
| Post-treatment Period | Protocol Violation | 0 | 0 | 0 | 0 | 1 |
| Post-treatment Period | Withdrawal by Subject | 2 | 4 | 0 | 1 | 2 |
| Treatment Period | Adverse Event | 0 | 1 | 0 | 0 | 1 |
| Treatment Period | Lost to Follow-up | 2 | 3 | 1 | 3 | 1 |
| Treatment Period | Not treated | 1 | 0 | 0 | 1 | 2 |
| Treatment Period | Physician Decision | 1 | 0 | 0 | 0 | 0 |
| Treatment Period | Protocol Violation | 2 | 1 | 0 | 1 | 2 |
| Treatment Period | Withdrawal by Subject | 6 | 4 | 1 | 4 | 1 |
Baseline characteristics
| Characteristic | Placebo | 5mg Galcanezumab | 50mg Galcanezumab | 120mg Galcanezumab | 300mg Galcanezumab | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 39.54 Years STANDARD_DEVIATION 12.1 | 41.40 Years STANDARD_DEVIATION 11.15 | 39.63 Years STANDARD_DEVIATION 12.42 | 40.57 Years STANDARD_DEVIATION 10.92 | 40.79 Years STANDARD_DEVIATION 13.2 | 40.24 Years STANDARD_DEVIATION 11.96 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 14 Participants | 11 Participants | 8 Participants | 14 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 117 Participants | 54 Participants | 57 Participants | 62 Participants | 53 Participants | 343 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Number of migraine headache days | 6.64 Days STANDARD_DEVIATION 2.73 | 6.68 Days STANDARD_DEVIATION 2.73 | 6.41 Days STANDARD_DEVIATION 2.66 | 6.95 Days STANDARD_DEVIATION 2.56 | 6.73 Days STANDARD_DEVIATION 2.48 | 6.68 Days STANDARD_DEVIATION 2.64 |
| Number of probable and migraine headache days | 8.04 Days STANDARD_DEVIATION 3.08 | 8.55 Days STANDARD_DEVIATION 3.23 | 8.33 Days STANDARD_DEVIATION 3.21 | 8.69 Days STANDARD_DEVIATION 3.46 | 8.01 Days STANDARD_DEVIATION 2.79 | 8.28 Days STANDARD_DEVIATION 3.15 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 16 Participants | 9 Participants | 23 Participants | 13 Participants | 75 Participants |
| Race (NIH/OMB) More than one race | 9 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 15 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 106 Participants | 49 Participants | 57 Participants | 43 Participants | 52 Participants | 307 Participants |
| Region of Enrollment United States | 137 Participants | 68 Participants | 68 Participants | 70 Participants | 67 Participants | 410 Participants |
| Sex: Female, Male Female | 109 Participants | 55 Participants | 61 Participants | 59 Participants | 56 Participants | 340 Participants |
| Sex: Female, Male Male | 28 Participants | 13 Participants | 7 Participants | 11 Participants | 11 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 137 | 20 / 68 | 18 / 68 | 23 / 70 | 19 / 67 | 6 / 125 | 2 / 61 | 2 / 66 | 2 / 63 | 3 / 65 |
| serious Total, serious adverse events | 0 / 137 | 0 / 68 | 0 / 68 | 1 / 70 | 1 / 67 | 0 / 125 | 1 / 61 | 0 / 66 | 0 / 63 | 1 / 65 |
Outcome results
Primary
Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase
The criteria for a migraine headache was adapted from the standard International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both (A and B) required features from the IHS ICHD-3 beta definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia.
Time frame: Baseline, 12 Weeks
Population: All participants with a valid 28-day baseline assessment of migraine headache days who received at least 1 dose of study treatment and had evaluable postbaseline headache data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | -3.66 Days | Standard Deviation 0.28 |
| 5mg Galcanezumab | Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | -4.23 Days | Standard Deviation 0.37 |
| 50mg Galcanezumab | Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | -3.92 Days | Standard Deviation 0.36 |
| 120mg Galcanezumab | Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | -4.80 Days | Standard Deviation 0.37 |
| 300mg Galcanezumab | Mean Change From Baseline in the Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | -4.28 Days | Standard Deviation 0.39 |
95% CI: [-1.4, 0.24]Bayesian Dose Response Model
95% CI: [-1.06, 0.56]Bayesian Dose Response Model
95% CI: [-2.02, -0.29]Bayesian Dose Response Model
95% CI: [-1.5, 0.27]Bayesian Dose Response Model
Secondary
Change From Baseline to 12 Week Endpoint in Migraine Specific Quality of Life (MSQL) Questionnaire Total Scores
MSQL consists of 14 questions across 3 dimensions (role function-restrictive, role function-preventive, and emotional function). All question values range from 1 to 6. Participants rated each item from 1 (none of the time) to 6 (all of the time). Since each item was presented as a negative statement, participant responses were recorded before item scores were calculated. Then, dimension scores were calculated as the sum of the recorded items for that specific dimension. Each dimension score was transformed into a score that ranged from 0 to 100. The transformation formula for the restrictive function = \[(dimension score-7)\*100\]/35, for the preventive function = \[(dimension score-4)\*100\]/20, and for the emotional function = \[(dimension score-3)\*100\]/15. A lower score indicated a poorer quality of life associated with that domain. LS means was determined by Analysis of covariance (ANCOVA) with treatment, pooled investigative site and baseline.
Time frame: Baseline, 12 Weeks
Population: All randomized participants who received at least 1 dose of study drug and have non-missing values at baseline and post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to 12 Week Endpoint in Migraine Specific Quality of Life (MSQL) Questionnaire Total Scores | 21.08 units on a scale | Standard Error 1.82 |
| 5mg Galcanezumab | Change From Baseline to 12 Week Endpoint in Migraine Specific Quality of Life (MSQL) Questionnaire Total Scores | 27.53 units on a scale | Standard Error 2.53 |
| 50mg Galcanezumab | Change From Baseline to 12 Week Endpoint in Migraine Specific Quality of Life (MSQL) Questionnaire Total Scores | 25.35 units on a scale | Standard Error 2.46 |
| 120mg Galcanezumab | Change From Baseline to 12 Week Endpoint in Migraine Specific Quality of Life (MSQL) Questionnaire Total Scores | 30.23 units on a scale | Standard Error 2.58 |
| 300mg Galcanezumab | Change From Baseline to 12 Week Endpoint in Migraine Specific Quality of Life (MSQL) Questionnaire Total Scores | 27.49 units on a scale | Standard Error 2.51 |
Secondary
Change From Baseline to 12 Week Endpoint in the Headache Impact Test-6™ (HIT-6™) Scores
The HIT-6 consists of 6 questions to measure the impact of headaches on the participants ability to function on the job, at school, at home and in social situations. A score to each question will be assigned as follows: never - 6, rarely - 8, sometimes - 10, very often - 11, and always - 13. The composite score is calculated as the sum of the scores for all 6 questions, the total score ranges between 36 and 78 with higher total scores reflecting more severe impact of headaches. LS means was determined by ANCOVA with treatment, pooled investigative site and baseline.
Time frame: Baseline, 12 Weeks
Population: All randomized participants who received at least 1 dose of study drug and have non-missing values at baseline and post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to 12 Week Endpoint in the Headache Impact Test-6™ (HIT-6™) Scores | -7.26 units on a scale | Standard Error 0.79 |
| 5mg Galcanezumab | Change From Baseline to 12 Week Endpoint in the Headache Impact Test-6™ (HIT-6™) Scores | -9.26 units on a scale | Standard Error 1.09 |
| 50mg Galcanezumab | Change From Baseline to 12 Week Endpoint in the Headache Impact Test-6™ (HIT-6™) Scores | -8.46 units on a scale | Standard Error 1.06 |
| 120mg Galcanezumab | Change From Baseline to 12 Week Endpoint in the Headache Impact Test-6™ (HIT-6™) Scores | -9.95 units on a scale | Standard Error 1.12 |
| 300mg Galcanezumab | Change From Baseline to 12 Week Endpoint in the Headache Impact Test-6™ (HIT-6™) Scores | -8.27 units on a scale | Standard Error 1.09 |
Secondary
Mean Change From Baseline in Number of Headache Hours in the Last 28-Day Period of the 12-Week Treatment Phase
Number of headache hours calculated as the total number of headache hours in a 28-day period on which a headache occurred. Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with treatment, pooled investigative site, period, and treatment-by-period interaction, baseline and baseline-by-period interaction.
Time frame: Baseline, 12 Weeks
Population: All participants with a valid 28-day baseline assessment of migraine headache days who received at least 1 dose of study treatment and had evaluable postbaseline headache data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Number of Headache Hours in the Last 28-Day Period of the 12-Week Treatment Phase | -16.56 Hours | Standard Error 1.73 |
| 5mg Galcanezumab | Mean Change From Baseline in Number of Headache Hours in the Last 28-Day Period of the 12-Week Treatment Phase | -20.15 Hours | Standard Error 2.45 |
| 50mg Galcanezumab | Mean Change From Baseline in Number of Headache Hours in the Last 28-Day Period of the 12-Week Treatment Phase | -19.38 Hours | Standard Error 2.35 |
| 120mg Galcanezumab | Mean Change From Baseline in Number of Headache Hours in the Last 28-Day Period of the 12-Week Treatment Phase | -22.29 Hours | Standard Error 2.39 |
| 300mg Galcanezumab | Mean Change From Baseline in Number of Headache Hours in the Last 28-Day Period of the 12-Week Treatment Phase | -24.45 Hours | Standard Error 2.42 |
Secondary
Mean Change From Baseline in Number of Migraine Attacks in the Last 28-Day Period of the 12-Week Treatment Phase
A migraine attack was defined as beginning on any day a migraine headache day was recorded and ending when a migraine headache-free day occurred. The criteria was adapted from the standard IHS ICHD-3 beta definition. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both (A and B) required features from the IHS ICHD-3 beta definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. Least Squares (LS) mean was calculated using mixed model repeated measures (MMRM) methodology with treatment, pooled investigative site, period, and treatment-by-period interaction, baseline and baseline-by-period interaction.
Time frame: Baseline, 12 Weeks
Population: All participants with a valid 28-day baseline assessment of migraine headache days who received at least 1 dose of study treatment and had evaluable postbaseline headache data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Number of Migraine Attacks in the Last 28-Day Period of the 12-Week Treatment Phase | -2.65 Migraine attacks | Standard Error 0.17 |
| 5mg Galcanezumab | Mean Change From Baseline in Number of Migraine Attacks in the Last 28-Day Period of the 12-Week Treatment Phase | -2.98 Migraine attacks | Standard Error 0.23 |
| 50mg Galcanezumab | Mean Change From Baseline in Number of Migraine Attacks in the Last 28-Day Period of the 12-Week Treatment Phase | -2.87 Migraine attacks | Standard Error 0.22 |
| 120mg Galcanezumab | Mean Change From Baseline in Number of Migraine Attacks in the Last 28-Day Period of the 12-Week Treatment Phase | -3.46 Migraine attacks | Standard Error 0.23 |
| 300mg Galcanezumab | Mean Change From Baseline in Number of Migraine Attacks in the Last 28-Day Period of the 12-Week Treatment Phase | -3.01 Migraine attacks | Standard Error 0.23 |
Secondary
Mean Change From Baseline in the Number of Days of Medication Use for the Treatment of Migraine Headache in the Last 28-Day Period of the 12-Week Treatment Phase
A migraine attack was defined as beginning on any day a migraine headache day was recorded and ending when a migraine headache-free day occurred. The criteria was adapted from the standard IHS ICHD-3 beta definition. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both (A and B) required features from the IHS ICHD-3 beta definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia. Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with treatment, pooled investigative site, period, and treatment-by-period interaction, baseline and baseline-by-period interaction.
Time frame: Baseline, 12 Weeks
Population: All participants with a valid 28-day baseline assessment of migraine headache days who received at least 1 dose of study treatment and had evaluable postbaseline headache data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Number of Days of Medication Use for the Treatment of Migraine Headache in the Last 28-Day Period of the 12-Week Treatment Phase | -2.51 Days | Standard Error 0.23 |
| 5mg Galcanezumab | Mean Change From Baseline in the Number of Days of Medication Use for the Treatment of Migraine Headache in the Last 28-Day Period of the 12-Week Treatment Phase | -3.27 Days | Standard Error 0.32 |
| 50mg Galcanezumab | Mean Change From Baseline in the Number of Days of Medication Use for the Treatment of Migraine Headache in the Last 28-Day Period of the 12-Week Treatment Phase | -2.58 Days | Standard Error 0.31 |
| 120mg Galcanezumab | Mean Change From Baseline in the Number of Days of Medication Use for the Treatment of Migraine Headache in the Last 28-Day Period of the 12-Week Treatment Phase | -3.59 Days | Standard Error 0.31 |
| 300mg Galcanezumab | Mean Change From Baseline in the Number of Days of Medication Use for the Treatment of Migraine Headache in the Last 28-Day Period of the 12-Week Treatment Phase | -3.15 Days | Standard Error 0.32 |
Secondary
Mean Change From Baseline in the Number of Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase
Number of calendar days on which a headache lasts ≥4 hours which includes migraines, probable migraines (PM) and nonmigraines. Criteria for migraine headache (MH) was adapted from standard IHS ICHD-3 beta definition. It is defined as headache with or without aura, of ≥30 min duration, and with both (A and B) required features from IHS ICHD-3 beta definition. Required feature A includes ≥2 of following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of following during headache: nausea and/or vomiting, or photophobia and phonophobia. PM is headache with or without aura, but missing 1 feature needed to fulfill all criteria for MH. LS means were calculated using MMRM with treatment, pooled investigative site, period, and treatment-by-period interaction, baseline and baseline-by-period interaction.
Time frame: Baseline, 12 Weeks
Population: All randomized participants with a valid 28-day baseline assessment of migraine headache days who received at least 1 dose of study treatment and had evaluable postbaseline headache data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Number of Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | -2.47 Days | Standard Error 0.22 |
| 5mg Galcanezumab | Mean Change From Baseline in the Number of Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | -2.81 Days | Standard Error 0.32 |
| 50mg Galcanezumab | Mean Change From Baseline in the Number of Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | -2.57 Days | Standard Error 0.3 |
| 120mg Galcanezumab | Mean Change From Baseline in the Number of Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | -3.11 Days | Standard Error 0.31 |
| 300mg Galcanezumab | Mean Change From Baseline in the Number of Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | -3.37 Days | Standard Error 0.31 |
Secondary
Mean Change From Baseline in the Number of Moderate-Severe Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase
Number of calendar days on which headache lasts ≥4 hrs it includes migraines, PM & non-migraines. MH is headache with or without aura, of ≥30 min duration, and with both (A and B) required features from IHS ICHD-3 beta definition. Required feature A includes ≥2 of following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of following during headache: nausea &/or vomiting, or photophobia & phonophobia. PM is headache with or without aura, but missing 1 feature needed to fulfill all criteria for MH. Severity was measured via interactive voice response system questionnaire What was the worst headache pain? For mild press 1. For moderate 2. For severe press 3. LSmean was calculated using MMRM with treatment, pooled investigative site, period, treatment-by-period interaction, baseline and baseline-by-period interaction.
Time frame: Baseline, 12 Weeks
Population: All participants with a valid 28-day baseline assessment of migraine headache days who received at least 1 dose of study treatment and had evaluable postbaseline headache data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Number of Moderate-Severe Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | -2.33 Days | Standard Error 0.2 |
| 5mg Galcanezumab | Mean Change From Baseline in the Number of Moderate-Severe Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | -2.49 Days | Standard Error 0.28 |
| 50mg Galcanezumab | Mean Change From Baseline in the Number of Moderate-Severe Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | -2.33 Days | Standard Error 0.27 |
| 120mg Galcanezumab | Mean Change From Baseline in the Number of Moderate-Severe Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | -2.88 Days | Standard Error 0.28 |
| 300mg Galcanezumab | Mean Change From Baseline in the Number of Moderate-Severe Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | -3.13 Days | Standard Error 0.28 |
Secondary
Percentage of Participants Developing Anti-drug Antibodies to Galcanezumab
The percent of participants with treatment emergent Anti-drug Antibodies (ADA) were assessed at week 1 to 12. A participant was considered to have treatment-emergent Galcanezumab ADA if the participant had at least 1 titer that was treatment-emergent relative to baseline, defined as any of the following: A negative baseline ADA result and a subsequent positive post-baseline ADA result with a titer \>=20; or a positive ADA results and a subsequent positive post-baseline ADA results with a 4-fold or greater increase in titer from the baseline measurement.
Time frame: Baseline through 12 Weeks
Population: All randomized participants who received at least 1 dose of study drug with non-missing baseline and postbaseline ADA measures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Developing Anti-drug Antibodies to Galcanezumab | 2.2 Percentage of participants |
| 5mg Galcanezumab | Percentage of Participants Developing Anti-drug Antibodies to Galcanezumab | 7.7 Percentage of participants |
| 50mg Galcanezumab | Percentage of Participants Developing Anti-drug Antibodies to Galcanezumab | 4.6 Percentage of participants |
| 120mg Galcanezumab | Percentage of Participants Developing Anti-drug Antibodies to Galcanezumab | 2.9 Percentage of participants |
| 300mg Galcanezumab | Percentage of Participants Developing Anti-drug Antibodies to Galcanezumab | 3.1 Percentage of participants |
Secondary
Percentage of Participants With ≥50% Reduction in Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase
The criteria for a migraine headache was adapted from the standard International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta definition. The definition of a migraine headache was a headache with or without aura, of ≥30 minutes (min) duration, and with both (A and B) required features from the IHS ICHD-3 beta definition. Required feature A includes at least 2 of the following headache characteristics: unilateral location, pulsatile quality, moderate or severe pain intensity, or aggravation by or causing avoidance of routine physical activity. Required feature B includes at least 1 of the following during the headache: nausea and/or vomiting, or photophobia and phonophobia.
Time frame: Week 12
Population: All participants with a valid 28-day baseline assessment of migraine headache days who received at least 1 dose of study treatment and had evaluable postbaseline headache data during the time period of analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With ≥50% Reduction in Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | 60.9 Percentage of participants |
| 5mg Galcanezumab | Percentage of Participants With ≥50% Reduction in Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | 75.4 Percentage of participants |
| 50mg Galcanezumab | Percentage of Participants With ≥50% Reduction in Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | 65.5 Percentage of participants |
| 120mg Galcanezumab | Percentage of Participants With ≥50% Reduction in Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | 76.5 Percentage of participants |
| 300mg Galcanezumab | Percentage of Participants With ≥50% Reduction in Number of Migraine Headache Days in the Last 28-Day Period of the 12-Week Treatment Phase | 70.1 Percentage of participants |
Secondary
Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores
The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The scale includes suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. Some questions are binary responses (yes/no) and some are on a scale of 1 (low severity) to 5 (high severity). Suicidal behavior: a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide.
Time frame: Baseline through Week 12
Population: All randomized participants who received at least 1 dose of study drug and with non-missing baseline and postbaseline C-SSRS assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | Suicidal Behavior | 0 Percentage of Participants |
| Placebo | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | Suicidal Ideation | 0 Percentage of Participants |
| 5mg Galcanezumab | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | Suicidal Behavior | 0 Percentage of Participants |
| 5mg Galcanezumab | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | Suicidal Ideation | 0 Percentage of Participants |
| 50mg Galcanezumab | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | Suicidal Ideation | 0 Percentage of Participants |
| 50mg Galcanezumab | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | Suicidal Behavior | 0 Percentage of Participants |
| 120mg Galcanezumab | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | Suicidal Ideation | 0 Percentage of Participants |
| 120mg Galcanezumab | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | Suicidal Behavior | 0 Percentage of Participants |
| 300mg Galcanezumab | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | Suicidal Behavior | 0 Percentage of Participants |
| 300mg Galcanezumab | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores | Suicidal Ideation | 1.52 Percentage of Participants |
Secondary
Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)
CGRP has been shown to be involved in the pathophysiology of migraine through dilation of cerebral and dural blood vessels, release of inflammatory mediators, and transmission of nociceptive (pain) information from intracranial blood vessels to the nervous system (Villalón and Olesen 2009). In migraineurs, serum concentrations of CGRP are significantly elevated during migraine attacks (Goadsby et al. 1990; Goadsby and Edvinsson 1993).
Time frame: 12 Weeks
Population: All randomized participants who received at least 1 dose of study drug with non-missing baseline and postbaseline measures for CGRP plasma concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | 0.1810 nanomoles per litre (nmol/L) | Standard Deviation 0.103 |
| 5mg Galcanezumab | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | 0.4750 nanomoles per litre (nmol/L) | Standard Deviation 0.394 |
| 50mg Galcanezumab | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | 1.5700 nanomoles per litre (nmol/L) | Standard Deviation 0.701 |
| 120mg Galcanezumab | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | 2.8000 nanomoles per litre (nmol/L) | Standard Deviation 1.22 |
| 300mg Galcanezumab | Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) | 3.8300 nanomoles per litre (nmol/L) | Standard Deviation 1.31 |
Secondary
Serum Concentration of Galcanezumab
Blood serum concentrations of galcanezumab.
Time frame: 12 Weeks
Population: All randomized participants who received at least 1 dose of study drug with non-missing baseline and postbaseline measures for serum concentration of galcanezumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Serum Concentration of Galcanezumab | 840 nanomoles per litre (nmol/L) | Standard Deviation 602 |
| 5mg Galcanezumab | Serum Concentration of Galcanezumab | 4650 nanomoles per litre (nmol/L) | Standard Deviation 2430 |
| 50mg Galcanezumab | Serum Concentration of Galcanezumab | 13200 nanomoles per litre (nmol/L) | Standard Deviation 7060 |
| 120mg Galcanezumab | Serum Concentration of Galcanezumab | 32100 nanomoles per litre (nmol/L) | Standard Deviation 19100 |