Episodic Migraine, Migraine
Conditions
Brief summary
The purpose of this study is to assess whether galcanezumab is superior to rimegepant in the prevention of migraine in participants with episodic migraine. The study duration will be approximately 6 months.
Interventions
DRUGGalcanezumab
Administered SC.
DRUGRimegepant
Administered orally.
DRUGPlacebo
Administered orally.
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of migraine, with or without aura, as determined by the study investigator and in consideration of International Headache Society International Classification of Headache Disorders - 3rd edition guidelines (ICHD-3 2018)
Exclusion criteria
* Have a known hypersensitivity to rimegepant or galcanezumab, and their excipients, monoclonal antibodies or other therapeutic proteins * Have acute cardiovascular events and/or serious cardiovascular risk, or have had myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft, or stroke within 6 months of screening, or have planned cardiovascular surgery or percutaneous coronary angioplasty. * Evidence of significant psychiatric disease by medical history, such as schizophrenia, personality disorders, or other serious mood or anxiety disorders. * Women who are pregnant or nursing * Current use or prior exposure to any calcitonin gene related peptide (CGRP) antagonist (small molecule or antibody) for any indication, including those who have previously completed or withdrawn from this study or any other study investigating a CGRP antagonist (small molecule or antibody)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With 50% Response Rate Across the 3-month Treatment Period. | Baseline, Month 1 through Month 3 | A migraine headache day is a calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of participants with at least a 50% reduction in monthly migraine headache days from baseline (50% response rate) using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly migraine headache day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With 100% Response Rate Across the 3-month Treatment Period. | Baseline, Month 1 through Month 3 | A migraine headache day is a calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of participants with at least a 100% reduction in monthly migraine headache days from baseline (100% response rate) using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly migraine headache day. |
| Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Across the 3-month Treatment Period. | Baseline, Month 1 through Month 3 | A migraine headache day is a calendar day on which a migraine headache or probable migraine headache occurred. Overall mean was derived from the average of month 1 through month 3. Least square (LS) mean was calculated using mixed model for repeated measures (MMRM) model with treatment, month, and treatment-by-month interaction as fixed effects and baseline number of migraine headache days, and baseline-by-month interaction as continuous variables. |
| Mean Change From Baseline in the Number of Monthly Migraine Headache Days at Month 1 | Baseline, Month 1 | A migraine headache day is a calendar day on which a migraine headache or probable migraine headache occurred. LS mean was calculated using MMRM model with treatment, month, and treatment-by-month interaction as fixed effects and baseline number of migraine headache days, and baseline-by-month interaction as continuous variables. |
| Mean Change From Baseline in the Number of Monthly Migraine Headache Days at Month 2 | Baseline, Month 2 | A migraine headache day is a calendar day on which a migraine headache or probable migraine headache occurred. LS mean was calculated using MMRM model with treatment, month, and treatment-by-month interaction as fixed effects and baseline number of migraine headache days, and baseline-by-month interaction as continuous variables. |
| Percentage of Participants With 75% Response Rate Across the 3-month Treatment Period. | Baseline, Month 1 through Month 3 | A migraine headache day is a calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of participants with at least a 75% reduction in monthly migraine headache days from baseline (75% response rate) using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly migraine headache day. |
| Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache Across the 3-month Treatment Period. | Baseline, Month 1 through Month 3 | Number of monthly migraine headache days requiring medication for the acute treatment of headache is defined as the number of calendar days in a 30-day period on which migraine or probable migraine occurs and acute medication is used. Overall mean was derived from the average of month 1 through month 3. LS mean was calculated using MMRM model with treatment, month, and treatment-by-month interaction as fixed effects and baseline number of migraine headache days with acute medications use, and baseline-by-month interaction as continuous variables. |
| Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) at Month 3 | Baseline, Month 3 | The MSQ v2.1 is a 14-item questionnaire, participant-rated scale with a 4-week recall period that measures the impact of migraine on work or daily activities, relationships with family & friends, leisure time, productivity, concentration, energy, tiredness & feelings. It consists of 14 items that address 3 domains: * Role Function-Restrictive (RF-R), items 1-7 * Role Function-Preventive (RF-P), items 8-11 * Emotional Function (EF), items 12-14 Each item is scored from 1 (none of the time) to 6 (all of the time) and are reverse coded (value 6 to 1). Raw scores for each domain are computed as a sum of item responses, with the collective sum providing a total raw score. These were transformed to a 0-100 scale, with higher scores indicating better quality of life. LS mean was calculated using Analysis of covariance (ANCOVA) with main effects of treatment, the baseline number of migraine headache days category (\<8 vs \>=8), and the continuous fixed covariate of the baseline endpoint. |
| Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score at Month 3 | Baseline, Month 3 | The MIDAS is a participant-rated scale that measures headache-related disability over a 3-month period. It consists of 5 items that measures number of days of work/school missed or days with productivity at work/school reduced to half or more; days with household work missed or days with productivity in household work reduced to half or more, and days of missed family/social/leisure activities. Each item has a numeric response range from 0 to 90 days; if days are missed from work/school or household work they are not counted as days with reduced productivity at work/school or household work. The numeric responses are summed to produce a total score ranging from 0 to 270. A higher value is indicative of more disability. LS mean was calculated using ANCOVA model with main effects of treatment, the baseline number of migraine headache days category (\<8 vs \>=8), and the continuous fixed covariate of the baseline endpoint. |
| Mean Change From Baseline in the Number of Monthly Migraine Headache Days at Month 3 | Baseline, Month 3 | A migraine headache day is a calendar day on which a migraine headache or probable migraine headache occurred. LS mean was calculated using MMRM model with treatment, month, and treatment-by-month interaction as fixed effects and baseline number of migraine headache days, and baseline-by-month interaction as continuous variables. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Galcanezumab Participants received a loading dose of 2 injections of 120 mg galcanezumab SC in the first month followed by 120 mg monthly for remaining 2 months.
1 placebo ODT every other day for 3 months was given to preserve blinding. | 287 |
| Rimegepant Participants received 75 mg Rimegepant ODT every other day for 3 months.
2 placebo SC injections loading dose, then 1 placebo SC injection monthly for remaining 2 months was given to preserve blinding. | 293 |
| Total | 580 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 4 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 5 | 8 |
| Overall Study | Physician Decision | 4 | 1 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Withdrawal by Subject | 14 | 13 |
Baseline characteristics
| Characteristic | Galcanezumab | Rimegepant | Total |
|---|---|---|---|
| Age, Continuous | 41.7 years STANDARD_DEVIATION 12.6 | 42.3 years STANDARD_DEVIATION 11.32 | 42.0 years STANDARD_DEVIATION 11.96 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 66 Participants | 65 Participants | 131 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 219 Participants | 223 Participants | 442 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 7 Participants |
| Number of Monthly Migraine Headache Days | 8.5 days per month STANDARD_DEVIATION 2.85 | 8.3 days per month STANDARD_DEVIATION 2.92 | 8.4 days per month STANDARD_DEVIATION 2.89 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 11 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 34 Participants | 44 Participants | 78 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 236 Participants | 232 Participants | 468 Participants |
| Region of Enrollment United States | 287 Participants | 293 Participants | 580 Participants |
| Sex: Female, Male Female | 244 Participants | 238 Participants | 482 Participants |
| Sex: Female, Male Male | 43 Participants | 55 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 287 | 0 / 293 |
| other Total, other adverse events | 28 / 287 | 28 / 293 |
| serious Total, serious adverse events | 0 / 287 | 1 / 293 |
Outcome results
Primary
Percentage of Participants With 50% Response Rate Across the 3-month Treatment Period.
A migraine headache day is a calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of participants with at least a 50% reduction in monthly migraine headache days from baseline (50% response rate) using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly migraine headache day.
Time frame: Baseline, Month 1 through Month 3
Population: All randomized participants who received at least one dose of study drug and had non-missing baseline value and at least one non-missing post-baseline value for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Galcanezumab | Percentage of Participants With 50% Response Rate Across the 3-month Treatment Period. | 62 percentage of participants |
| Rimegepant | Percentage of Participants With 50% Response Rate Across the 3-month Treatment Period. | 61 percentage of participants |
p-value: 0.69595% CI: [0.81, 1.38]pseudo likelihood-based repeated measure
Secondary
Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) at Month 3
The MSQ v2.1 is a 14-item questionnaire, participant-rated scale with a 4-week recall period that measures the impact of migraine on work or daily activities, relationships with family & friends, leisure time, productivity, concentration, energy, tiredness & feelings. It consists of 14 items that address 3 domains: * Role Function-Restrictive (RF-R), items 1-7 * Role Function-Preventive (RF-P), items 8-11 * Emotional Function (EF), items 12-14 Each item is scored from 1 (none of the time) to 6 (all of the time) and are reverse coded (value 6 to 1). Raw scores for each domain are computed as a sum of item responses, with the collective sum providing a total raw score. These were transformed to a 0-100 scale, with higher scores indicating better quality of life. LS mean was calculated using Analysis of covariance (ANCOVA) with main effects of treatment, the baseline number of migraine headache days category (\<8 vs \>=8), and the continuous fixed covariate of the baseline endpoint.
Time frame: Baseline, Month 3
Population: All randomized participants who received at least one dose of study drug and had non-missing baseline value and at least one non-missing post-baseline value for this outcome.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Galcanezumab | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) at Month 3 | Total score | 28.92 score on a scale | Standard Error 1.07 |
| Galcanezumab | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) at Month 3 | RF-R | 31.90 score on a scale | Standard Error 1.2 |
| Galcanezumab | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) at Month 3 | RF-P | 24.62 score on a scale | Standard Error 1.02 |
| Galcanezumab | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) at Month 3 | EF | 27.76 score on a scale | Standard Error 1.17 |
| Rimegepant | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) at Month 3 | EF | 24.58 score on a scale | Standard Error 1.17 |
| Rimegepant | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) at Month 3 | Total score | 24.53 score on a scale | Standard Error 1.07 |
| Rimegepant | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) at Month 3 | RF-P | 20.74 score on a scale | Standard Error 1.02 |
| Rimegepant | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) at Month 3 | RF-R | 26.66 score on a scale | Standard Error 1.2 |
Comparison: Total score95% CI: [1.42, 7.37]ANCOVA
Comparison: RF-R95% CI: [1.9, 8.58]ANCOVA
Comparison: RF-P95% CI: [1.06, 6.71]ANCOVA
Comparison: EF95% CI: [-0.08, 6.44]ANCOVA
Secondary
Mean Change From Baseline in the Number of Monthly Migraine Headache Days at Month 1
A migraine headache day is a calendar day on which a migraine headache or probable migraine headache occurred. LS mean was calculated using MMRM model with treatment, month, and treatment-by-month interaction as fixed effects and baseline number of migraine headache days, and baseline-by-month interaction as continuous variables.
Time frame: Baseline, Month 1
Population: All randomized participants who received at least one dose of study drug and had non-missing baseline value and at least one non-missing post-baseline value for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Galcanezumab | Mean Change From Baseline in the Number of Monthly Migraine Headache Days at Month 1 | -4.33 days per month | Standard Error 0.2 |
| Rimegepant | Mean Change From Baseline in the Number of Monthly Migraine Headache Days at Month 1 | -3.77 days per month | Standard Error 0.2 |
95% CI: [-1.11, 0]Mixed Models Analysis
Secondary
Mean Change From Baseline in the Number of Monthly Migraine Headache Days at Month 2
A migraine headache day is a calendar day on which a migraine headache or probable migraine headache occurred. LS mean was calculated using MMRM model with treatment, month, and treatment-by-month interaction as fixed effects and baseline number of migraine headache days, and baseline-by-month interaction as continuous variables.
Time frame: Baseline, Month 2
Population: All randomized participants who received at least one dose of study drug and had non-missing baseline value and at least one non-missing post-baseline value for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Galcanezumab | Mean Change From Baseline in the Number of Monthly Migraine Headache Days at Month 2 | -4.81 days per month | Standard Error 0.2 |
| Rimegepant | Mean Change From Baseline in the Number of Monthly Migraine Headache Days at Month 2 | -4.44 days per month | Standard Error 0.19 |
95% CI: [-0.9, 0.18]Mixed Models Analysis
Secondary
Mean Change From Baseline in the Number of Monthly Migraine Headache Days at Month 3
A migraine headache day is a calendar day on which a migraine headache or probable migraine headache occurred. LS mean was calculated using MMRM model with treatment, month, and treatment-by-month interaction as fixed effects and baseline number of migraine headache days, and baseline-by-month interaction as continuous variables.
Time frame: Baseline, Month 3
Population: All randomized participants who received at least one dose of study drug and had non-missing baseline value and at least one non-missing post-baseline value for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Galcanezumab | Mean Change From Baseline in the Number of Monthly Migraine Headache Days at Month 3 | -5.13 days per month | Standard Error 0.2 |
| Rimegepant | Mean Change From Baseline in the Number of Monthly Migraine Headache Days at Month 3 | -4.94 days per month | Standard Error 0.2 |
95% CI: [-0.73, 0.37]Mixed Models Analysis
Secondary
Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score at Month 3
The MIDAS is a participant-rated scale that measures headache-related disability over a 3-month period. It consists of 5 items that measures number of days of work/school missed or days with productivity at work/school reduced to half or more; days with household work missed or days with productivity in household work reduced to half or more, and days of missed family/social/leisure activities. Each item has a numeric response range from 0 to 90 days; if days are missed from work/school or household work they are not counted as days with reduced productivity at work/school or household work. The numeric responses are summed to produce a total score ranging from 0 to 270. A higher value is indicative of more disability. LS mean was calculated using ANCOVA model with main effects of treatment, the baseline number of migraine headache days category (\<8 vs \>=8), and the continuous fixed covariate of the baseline endpoint.
Time frame: Baseline, Month 3
Population: All randomized participants who received at least one dose of study drug and had non-missing baseline value and at least one non-missing post-baseline value for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Galcanezumab | Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score at Month 3 | -22.54 score on a scale | Standard Error 1.63 |
| Rimegepant | Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score at Month 3 | -20.11 score on a scale | Standard Error 1.63 |
95% CI: [-6.94, 2.08]ANCOVA
Secondary
Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Across the 3-month Treatment Period.
A migraine headache day is a calendar day on which a migraine headache or probable migraine headache occurred. Overall mean was derived from the average of month 1 through month 3. Least square (LS) mean was calculated using mixed model for repeated measures (MMRM) model with treatment, month, and treatment-by-month interaction as fixed effects and baseline number of migraine headache days, and baseline-by-month interaction as continuous variables.
Time frame: Baseline, Month 1 through Month 3
Population: All randomized participants who received at least one dose of study drug and had non-missing baseline value and at least one non-missing post-baseline value for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Galcanezumab | Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Across the 3-month Treatment Period. | -4.75 days per month | Standard Error 0.17 |
| Rimegepant | Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Across the 3-month Treatment Period. | -4.39 days per month | Standard Error 0.16 |
95% CI: [-0.82, 0.09]Mixed Models Analysis
Secondary
Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache Across the 3-month Treatment Period.
Number of monthly migraine headache days requiring medication for the acute treatment of headache is defined as the number of calendar days in a 30-day period on which migraine or probable migraine occurs and acute medication is used. Overall mean was derived from the average of month 1 through month 3. LS mean was calculated using MMRM model with treatment, month, and treatment-by-month interaction as fixed effects and baseline number of migraine headache days with acute medications use, and baseline-by-month interaction as continuous variables.
Time frame: Baseline, Month 1 through Month 3
Population: All randomized participants who received at least one dose of study drug and had non-missing baseline value and at least one non-missing post-baseline value for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Galcanezumab | Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache Across the 3-month Treatment Period. | -3.95 days per month | Standard Error 0.14 |
| Rimegepant | Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache Across the 3-month Treatment Period. | -3.47 days per month | Standard Error 0.13 |
95% CI: [-0.86, -0.11]Mixed Models Analysis
Secondary
Percentage of Participants With 100% Response Rate Across the 3-month Treatment Period.
A migraine headache day is a calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of participants with at least a 100% reduction in monthly migraine headache days from baseline (100% response rate) using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly migraine headache day.
Time frame: Baseline, Month 1 through Month 3
Population: All randomized participants who received at least one dose of study drug and had non-missing baseline value and at least one non-missing post-baseline value for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Galcanezumab | Percentage of Participants With 100% Response Rate Across the 3-month Treatment Period. | 18 percentage of participants |
| Rimegepant | Percentage of Participants With 100% Response Rate Across the 3-month Treatment Period. | 15 percentage of participants |
95% CI: [0.89, 1.79]pseudo likelihood-based repeated measure
Secondary
Percentage of Participants With 75% Response Rate Across the 3-month Treatment Period.
A migraine headache day is a calendar day on which a migraine headache or probable migraine headache occurred. Overall mean percentage across months 1 through 3 of participants with at least a 75% reduction in monthly migraine headache days from baseline (75% response rate) using a categorical pseudo likelihood-based repeated measures model for binary responder indicator with fixed, categorical effects of treatment, month, treatment by month, and continuous, fixed covariate of baseline monthly migraine headache day.
Time frame: Baseline, Month 1 through Month 3
Population: All randomized participants who received at least one dose of study drug and had non-missing baseline value and at least one non-missing post-baseline value for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Galcanezumab | Percentage of Participants With 75% Response Rate Across the 3-month Treatment Period. | 37 percentage of participants |
| Rimegepant | Percentage of Participants With 75% Response Rate Across the 3-month Treatment Period. | 33 percentage of participants |
95% CI: [0.89, 1.56]pseudo likelihood-based repeated measure