Migraine
Conditions
Keywords
AMG334, erenumab, migraine, chronic, headache, Chinese
Brief summary
The purpose of this study was to evaluate the efficacy and safety of erenumab in patients with chronic migraine in Asian population.
Detailed description
This study used a single-cohort, 2-treatment arms, randomized (1:1 (70 mg:placebo)), double-blind study design in adult subjects with chronic migraine. A screening period of 2 weeks was used to assess initial eligibility, followed by a 4-week baseline period to assess diary compliance and headache frequency. Eligible patients were then randomized to either erenumab 70 mg or placebo for 12 weeks, followed by an open-label treatment period to last until end of PTA determined by the product launch in the country or the country's decision not to launch. A safety follow-up visit occurred 12 weeks after the last treatment for subjects who discontinue the double-blind treatment or who completed the double-blind treatment period without continuing in the open-label treatment period.
Interventions
BIOLOGICALErenumab
Administered by pre-filled syringe
OTHERPlacebo
Administered by pre-filled syringe
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
key inclusion Criteria: 1. History of at least 5 attacks of migraine 2. ≥ 15 headache days of which ≥ 8 headache days meet criteria as migraine days during the baseline period 3. \>=80% diary compliance during the baseline period Key
Exclusion criteria
1. Older than 50 years of age at migraine onset 2. History of cluster or hemiplegic headache 3. Evidence of seizure or major psychiatric disorder 4. Cardiac or active hepatic disease 5. Pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Monthly Migraine Days During the Last 4 Weeks of the 12-week Treatment Period | baseline (4 weeks period prior to start of study drug), week 9 to 12 | A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined as a migraine with or without aura, lasting for ≥4 continuous hours, and meeting at least one of the following criteria: 1. ≥2 of the following pain features: * Unilateral * Throbbing * Moderate to severe * Exacerbated with exercise/physical activity 2. ≥1 of the following associated symptoms: * Nausea and/or vomiting * Photophobia and phonophobia |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Migraine-related Disability and Productivity as Measured by the mMIDAS During the Last 4 Weeks of the 12-week Treatment Period | baseline (4 weeks period prior to start of study drug), week 9 to 12 | The modified MIDAS is a 5-item self-administered questionnaire that sums the number of productive days lost over the past month in two settings: the workplace and the home. The MIDAS also assesses disability in family, social, and leisure activities. The MIDAS score is the sum of missed days due to a headache from paid work, housework, and non-work (family, social, leisure) activities; and days at paid work or housework where productivity was reduced by at least half. |
| Number of Participants With at Least 50% Reduction From Baseline in Monthly Migraine Days During the Last 4 Weeks of the 12-week Treatment Period | baseline (4 weeks period prior to start of study drug), week 9 to 12 | A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined as a migraine with or without aura, lasting for ≥4 continuous hours, and meeting at least one of the following criteria: 1. ≥2 of the following pain features: * Unilateral * Throbbing * Moderate to severe * Exacerbated with exercise/physical activity 2. ≥1 of the following associated symptoms: * Nausea and/or vomiting * Photophobia and phonophobia |
| Change From Baseline in Monthly Acute Headache Medication Days During the Last 4 Weeks of the 12-week Treatment Period | baseline (4 weeks period prior to start of study drug), week 9 to 12 | An acute headache medication day was defined as a day when medication was taken to treat acute headache. |
| Number of Subjects With Adverse Events as a Measure of Safety | DBTP: 12 weeks for participants entering the OLTP. 20 weeks for participants NOT entering the OLTP. OLTP: From week 12 until up to approximately 4 years. | Number of subjects with adverse events was assessed separately in the double-blind treatment period (DBTP) and the open-label treatment period (OLTP). |
| Number of Subjects With Anti-AMG 334 Antibodies | baseline, 20 weeks | anti-AMG 334 antibodies assessed for binding and neutralizing) |
Countries
China, India, Malaysia, Philippines, Singapore, South Korea, Taiwan, Thailand, Vietnam
Participant flow
Pre-assignment details
A screening period of 2 weeks was used to assess initial eligibility, followed by a 4-week baseline period to assess diary compliance and headache frequency.
Participants by arm
| Arm | Count |
|---|---|
| Erenumab 70 mg Administered by pre-filled syringe at Day 1 and Weeks 4 and 8 | 279 |
| Placebo Administered by pre-filled syringe at Day 1 and Weeks 4 and 8 | 278 |
| Total | 557 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Period Until Week 12 | Adverse Event | 2 | 1 |
| Double-Blind Period Until Week 12 | Lack of Efficacy | 1 | 0 |
| Double-Blind Period Until Week 12 | Pregnancy | 1 | 1 |
| Double-Blind Period Until Week 12 | Protocol Violation | 1 | 2 |
| Double-Blind Period Until Week 12 | Withdrawal by Subject | 1 | 2 |
| Open-Label Period From Week 12 | Adverse Event | 5 | 11 |
| Open-Label Period From Week 12 | Lost to Follow-up | 1 | 0 |
| Open-Label Period From Week 12 | New Therapy for Study Indication | 1 | 0 |
| Open-Label Period From Week 12 | No longer clinically benefiting | 12 | 10 |
| Open-Label Period From Week 12 | Physician Decision | 6 | 3 |
| Open-Label Period From Week 12 | Pregnancy | 2 | 2 |
| Open-Label Period From Week 12 | Protocol Violation | 2 | 0 |
| Open-Label Period From Week 12 | Withdrawal by Subject | 90 | 85 |
Baseline characteristics
| Characteristic | Placebo | Total | Erenumab 70 mg |
|---|---|---|---|
| Age, Continuous | 41.9 years STANDARD_DEVIATION 10.9 | 41.7 years STANDARD_DEVIATION 10.9 | 41.4 years STANDARD_DEVIATION 10.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 275 Participants | 552 Participants | 277 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 237 Participants | 454 Participants | 217 Participants |
| Sex: Female, Male Male | 41 Participants | 103 Participants | 62 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 | 0 / 279 | 0 / 278 | 0 / 224 | 0 / 232 |
| other Total, other adverse events | 58 / 279 | 59 / 278 | 92 / 224 | 120 / 232 |
| serious Total, serious adverse events | 7 / 279 | 7 / 278 | 21 / 224 | 24 / 232 |
Outcome results
Primary
Change From Baseline in Monthly Migraine Days During the Last 4 Weeks of the 12-week Treatment Period
A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined as a migraine with or without aura, lasting for ≥4 continuous hours, and meeting at least one of the following criteria: 1. ≥2 of the following pain features: * Unilateral * Throbbing * Moderate to severe * Exacerbated with exercise/physical activity 2. ≥1 of the following associated symptoms: * Nausea and/or vomiting * Photophobia and phonophobia
Time frame: baseline (4 weeks period prior to start of study drug), week 9 to 12
Population: Full Analysis Set. All randomized participants with evaluable measurements at the respective timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Erenumab 70 mg | Change From Baseline in Monthly Migraine Days During the Last 4 Weeks of the 12-week Treatment Period | -8.19 days | Standard Error 0.46 |
| Placebo | Change From Baseline in Monthly Migraine Days During the Last 4 Weeks of the 12-week Treatment Period | -6.62 days | Standard Error 0.45 |
p-value: 0.01595% CI: [-2.83, -0.3]Mixed Models Analysis
Secondary
Change From Baseline in Migraine-related Disability and Productivity as Measured by the mMIDAS During the Last 4 Weeks of the 12-week Treatment Period
The modified MIDAS is a 5-item self-administered questionnaire that sums the number of productive days lost over the past month in two settings: the workplace and the home. The MIDAS also assesses disability in family, social, and leisure activities. The MIDAS score is the sum of missed days due to a headache from paid work, housework, and non-work (family, social, leisure) activities; and days at paid work or housework where productivity was reduced by at least half.
Time frame: baseline (4 weeks period prior to start of study drug), week 9 to 12
Population: Full Analysis Set. All randomized participants with evaluable measurements at the respective timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Erenumab 70 mg | Change From Baseline in Migraine-related Disability and Productivity as Measured by the mMIDAS During the Last 4 Weeks of the 12-week Treatment Period | -14.67 days | Standard Error 1.2 |
| Placebo | Change From Baseline in Migraine-related Disability and Productivity as Measured by the mMIDAS During the Last 4 Weeks of the 12-week Treatment Period | -12.93 days | Standard Error 1.19 |
Secondary
Change From Baseline in Monthly Acute Headache Medication Days During the Last 4 Weeks of the 12-week Treatment Period
An acute headache medication day was defined as a day when medication was taken to treat acute headache.
Time frame: baseline (4 weeks period prior to start of study drug), week 9 to 12
Population: Full Analysis Set. All randomized participants with evaluable measurements at the respective timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Erenumab 70 mg | Change From Baseline in Monthly Acute Headache Medication Days During the Last 4 Weeks of the 12-week Treatment Period | -5.34 days | Standard Error 0.39 |
| Placebo | Change From Baseline in Monthly Acute Headache Medication Days During the Last 4 Weeks of the 12-week Treatment Period | -4.66 days | Standard Error 0.39 |
Secondary
Number of Participants With at Least 50% Reduction From Baseline in Monthly Migraine Days During the Last 4 Weeks of the 12-week Treatment Period
A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined as a migraine with or without aura, lasting for ≥4 continuous hours, and meeting at least one of the following criteria: 1. ≥2 of the following pain features: * Unilateral * Throbbing * Moderate to severe * Exacerbated with exercise/physical activity 2. ≥1 of the following associated symptoms: * Nausea and/or vomiting * Photophobia and phonophobia
Time frame: baseline (4 weeks period prior to start of study drug), week 9 to 12
Population: Full Analysis Set. All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Erenumab 70 mg | Number of Participants With at Least 50% Reduction From Baseline in Monthly Migraine Days During the Last 4 Weeks of the 12-week Treatment Period | 131 Participants |
| Placebo | Number of Participants With at Least 50% Reduction From Baseline in Monthly Migraine Days During the Last 4 Weeks of the 12-week Treatment Period | 102 Participants |
Secondary
Number of Subjects With Adverse Events as a Measure of Safety
Number of subjects with adverse events was assessed separately in the double-blind treatment period (DBTP) and the open-label treatment period (OLTP).
Time frame: DBTP: 12 weeks for participants entering the OLTP. 20 weeks for participants NOT entering the OLTP. OLTP: From week 12 until up to approximately 4 years.
Population: Safety Set (for DBTP). Number of participants entering the OLTP (for OLTP).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Erenumab 70 mg | Number of Subjects With Adverse Events as a Measure of Safety | Double-Blind Treatment Period: Number of subjects with at least one AE | 127 Participants |
| Erenumab 70 mg | Number of Subjects With Adverse Events as a Measure of Safety | Open-Label Treatment Period: Number of subjects with at least one AE | 152 Participants |
| Placebo | Number of Subjects With Adverse Events as a Measure of Safety | Double-Blind Treatment Period: Number of subjects with at least one AE | 132 Participants |
| Placebo | Number of Subjects With Adverse Events as a Measure of Safety | Open-Label Treatment Period: Number of subjects with at least one AE | 176 Participants |
Secondary
Number of Subjects With Anti-AMG 334 Antibodies
anti-AMG 334 antibodies assessed for binding and neutralizing)
Time frame: baseline, 20 weeks
Population: FAS including participants with a valid assessment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Erenumab 70 mg | Number of Subjects With Anti-AMG 334 Antibodies | Neutralizing antibody positive at any time from baseline to week 20 | 1 Participants |
| Erenumab 70 mg | Number of Subjects With Anti-AMG 334 Antibodies | Binding antibody positive at baseline | 0 Participants |
| Erenumab 70 mg | Number of Subjects With Anti-AMG 334 Antibodies | Neutralizing antibody positive at baseline | 0 Participants |
| Erenumab 70 mg | Number of Subjects With Anti-AMG 334 Antibodies | Binding antibody positive at any time from baseline to week 20 | 9 Participants |
| Placebo | Number of Subjects With Anti-AMG 334 Antibodies | Binding antibody positive at any time from baseline to week 20 | 0 Participants |
| Placebo | Number of Subjects With Anti-AMG 334 Antibodies | Neutralizing antibody positive at any time from baseline to week 20 | 0 Participants |
| Placebo | Number of Subjects With Anti-AMG 334 Antibodies | Neutralizing antibody positive at baseline | 0 Participants |
| Placebo | Number of Subjects With Anti-AMG 334 Antibodies | Binding antibody positive at baseline | 0 Participants |