Migraine
Conditions
Keywords
Episodic and Chronic Migraine, Link between clinical response and biomarker, Phase 4
Brief summary
To explore the relationship between clinical response to erenumab and genetic biomarkers
Detailed description
This is a phase 4 open-label study aiming to explore the relationship between clinical response to erenumab and genetic biomarkers. Subjects with episodic or chronic migraine will be treated with Erenumab 70mg or 140mg for a 4-week baseline/screening period, followed by a 24-week treatment period. Subjects will collect migraine-related parameters daily using an eDiary and blood samples will be collected for biomarker research. All analysis will be descriptive in nature.
Interventions
DRUGErenumab
Erenumab 70 mg or 140 mg packed in a SureClick® Autoinjector Pen (AI).
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Subject has provided informed consent prior to initiation of any study-specific activities/procedures * Age greater than or equal to 18 years upon entry into screening * History of migraine (with or without aura) for greater than or equal to 12 months before screening according to the International Headache Society (IHS) Classification ICHD-3 (Headache Classification Committee of the International Headache Society, 2018) based on medical records and/or patient self report * Greater than or equal to 4 headache days that meet criteria as migraine days per month on average across the 3 months before screening After baseline period * Must have demonstrated greater than or equal to 75% compliance in eDiary usage during baseline period
Exclusion criteria
Subjects are excluded from the study if any of the following criteria apply: Disease Related * Greater than 50 years of age at migraine onset * History of cluster headache or hemiplegic migraine headache * Inability to differentiate between migraine from other headaches. Other Medical Conditions * The subject is at risk of self-harm or harm to others as evidenced by past suicidal behaviour * History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. Prior/Concomitant Therapy * Previously received erenumab (Aimovig®) * Received an anti-CGRP monoclonal antibody within 3 months prior to the start of the baseline period * Initiation, discontinuation, or change of dosing of migraine prophylactic medications within 2 months prior to the start of the baseline period, during the baseline period or planned during the study. Prior/Concurrent Clinical Study Experience • Currently receiving treatment in another investigational device or drug study, or less than 30 days or 5 half-lives since ending treatment on another investigational device or drug study (ies). Other investigational procedures while participating in this study are excluded. Other Exclusions * Female subjects of childbearing potential with a positive pregnancy test assessed at screening or day 1 by a urine pregnancy test * Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 16 weeks after the last dose of investigational product * Female subjects of childbearing potential unwilling to use 1 acceptable method of effective contraception during treatment and for an additional 16 weeks after the last dose of investigational product * Evidence of current pregnancy or breastfeeding per subject self-report or medical records * Subject has known sensitivity to any of the products or components to be administered during dosing * Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (e.g, Clinical Outcome Assessments) to the best of the subject and investigator's knowledge
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Mean MMDs Over Months 4, 5, and 6 in Relation to mPRS | 4-week Baseline Period and the last 3 months (Months 4, 5, and 6) of the 24-week Open-label Treatment Period | A migraine day was defined as a calendar day (00:00 to 23:59) in which the participant reports any migraine headache or takes any triptan-based acute migraine-specific medication. At least a 50% reduction from Baseline in MMDs was determined if: (average number of migraine days per month during the last 3 months \[months 4, 5, and 6\] of the 24-week Open-label Treatment Period minus number of migraine days during the 4-week Baseline Period) / number of migraine days during the 4-week Baseline Period \* 100, was less than or equal to -50%. |
Countries
Denmark, Iceland
Participant flow
Recruitment details
A total of 1406 participants were enrolled in Denmark and Iceland between October 2020 and January 2023. As pre-specified, the primary objective of the study was to assess the relationship between migraine polygenic risk score (mPRS) and the reduction in mean monthly migraine days (MMD) after using erenumab, regardless of erenumab dose received.
Pre-assignment details
The study consisted of the following: * A Screening Period of up to 3 weeks. * A Baseline Period of 4 - 5 weeks to collect data on migraine headaches and acute headache medication use. * A 24-week, Open-label Treatment Period.
Participants by arm
| Arm | Count |
|---|---|
| Erenumab 70 mg/140 mg Participants were enrolled into the Open-label Treatment Period and received erenumab 70 mg or 140 mg administered SC Q4W at the discretion of the investigator. Per protocol, dose switching between erenumab 70 mg and 140 mg was permitted at Week 12. However, participants could switch dose before or after Week 12 if needed based on investigator discretion.
Dose comparison was not pre-specified. | 1,406 |
| Total | 1,406 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Decision by sponsor | 2 |
| Overall Study | Lost to Follow-up | 11 |
| Overall Study | Withdrawal by Subject | 39 |
Baseline characteristics
| Characteristic | Erenumab 70 mg/140 mg |
|---|---|
| Age, Continuous | 42.5 years STANDARD_DEVIATION 11.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1384 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| MMDs During the Baseline Period | 12.82 days / month STANDARD_DEVIATION 5.92 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants |
| Race/Ethnicity, Customized Asian | 17 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants |
| Race/Ethnicity, Customized Multiple | 9 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Other | 23 Participants |
| Race/Ethnicity, Customized White | 1353 Participants |
| Sex: Female, Male Female | 1228 Participants |
| Sex: Female, Male Male | 178 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 214 | 0 / 497 | 0 / 7 | 0 / 688 |
| other Total, other adverse events | 172 / 214 | 391 / 497 | 7 / 7 | 417 / 688 |
| serious Total, serious adverse events | 8 / 214 | 8 / 497 | 1 / 7 | 14 / 688 |
Outcome results
Primary
Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Mean MMDs Over Months 4, 5, and 6 in Relation to mPRS
A migraine day was defined as a calendar day (00:00 to 23:59) in which the participant reports any migraine headache or takes any triptan-based acute migraine-specific medication. At least a 50% reduction from Baseline in MMDs was determined if: (average number of migraine days per month during the last 3 months \[months 4, 5, and 6\] of the 24-week Open-label Treatment Period minus number of migraine days during the 4-week Baseline Period) / number of migraine days during the 4-week Baseline Period \* 100, was less than or equal to -50%.
Time frame: 4-week Baseline Period and the last 3 months (Months 4, 5, and 6) of the 24-week Open-label Treatment Period
Population: Efficacy Analysis Set: consisted of a subset of participants in FAS who received at least 1 dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erenumab 70 mg/140 mg | Percentage of Participants Achieving at Least a 50% Reduction From Baseline in Mean MMDs Over Months 4, 5, and 6 in Relation to mPRS | 54.9 percentage of participants |
Comparison: Odds of achieving at least 50% reduction from Baseline in mean MMD over months 4, 5, and 6 in relation to mPRS.p-value: 0.8695% CI: [0.9, 1.13]Regression, Logistic