Episodic Migraine
Conditions
Keywords
AMG334, erenumab, episodic migraine, headache, CGRP, Calcitonin Gene-related, migraine, adult
Brief summary
This study is to evaluate the efficacy and safety of AMG334 in adult patients with episodic migraine
Detailed description
This study used a single-cohort, 3-treatment arm, randomized, double-blind study design in adult patients with episodic migraine. The subjects were randomized to receive either erenumab or placebo in a 2:3:3 ratio (erenumab 140 mg: erenumab 70 mg: placebo). A screening period of 2 weeks was used to assess initial eligibility, followed by a 4-week baseline period. After randomization/Day 1, visits occurred at four week intervals until Week 12, which was the End of Treatment. The final visit, Last Patient Last Visit was a Safety Follow-Up visit, which occurred 12 weeks later, at Week 24.
Interventions
BIOLOGICALErenumab
70 mg/mL pre-filled syringe administered subcutaneously
OTHERPlacebo
Matching placebo in pre-filled syringe administered subcutaneously
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key inclusion criteria: 1. Documented history of migraine in the 12 months prior to screening 2. 4-14 days per month of migraine symptoms 3. \>=80% diary compliance during the Baseline period Key
Exclusion criteria
1. \>50 years old at migraine onset 2. Pregnant or nursing 3. History of cluster or hemiplegic headache 4. Evidence of seizure or major psychiatric disorder 5. Score of 19 or higher on the BDI 6. Active chronic pain syndrome 7. Cardiac or hepatic disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Monthly Migraine Days at the Last Month (Month 3) of the Double-blind Treatment Period (DBTP) | Baseline up to Month 3 | A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: 1. ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity 2. ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Month 3 | Baseline and at Month 3 | Achievement of at least a 50% reduction from baseline in monthly migraine days at Month 3. A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: 1. ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity 2. ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia |
| Change From Baseline in Acute Migraine-specific Medication Treatment Days at Month 3 | Baseline up to Month 3 | Number of days on which acute migraine-specific medications were used were recorded in eDiary between each monthly IP dose. Migraine-Specific medications include two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications. Monthly migraine-specific medication use at baseline is the number of migraine-specific medication treatment days in the baseline period. |
| Change From Baseline in Headache Impact Scores as Measured by the Headache Impact Test (HIT-6) at Month 3 | Baseline up to Month 3 | The HIT-6 is a short-form self-administered questionnaire based on the internet-HIT question pool. The HIT-6 was developed as a global measure of adverse headache impact to assess headache severity in the previous month and change in a patient's clinical status over a short period of time. Six items assess the frequency of pain severity, headaches limiting daily activity (household, work, school, and social). Each of the 6 questions is responded to using 1 of 5 response categories: never, rarely, sometimes, very often, or always. For each HIT-6 item, 6, 8, 10, 11, or 13 points, respectively, are assigned to the response provided. These points were summed to produce a total HIT-6 score that ranges from 36 to 78. Scores were categorized into 4 grades, representing little or no impact (49 or less), some impact (50-55), substantial impact (56-59), and severe impact (60-78) due to headache. Lower values represent better outcomes, therefore negative change denotes improveme |
Countries
Argentina, India, Lebanon, Malaysia, Mexico, Philippines, Singapore, South Korea, Taiwan, Thailand, Vietnam
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AMG334 70 mg AMG334 70 mg: one pre-filled syringe containing 70 mg of erenumab plus one pre-filled syringe of identical placebo administered subcutaneous every 28 days | 338 |
| AMG334 140 mg AMG334 140 mg: two pre-filled syringe containing 70 mg each of erenumab administered subcutaneous every 28 days | 224 |
| Placebo Two pre-filled syringes containing placebo identical in appearance to erenumab | 338 |
| Total | 900 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Treatment Period (DBTP) | Adverse Event | 0 | 0 | 2 |
| Double-blind Treatment Period (DBTP) | Lost to Follow-up | 0 | 0 | 1 |
| Double-blind Treatment Period (DBTP) | Physician Decision | 4 | 0 | 1 |
| Double-blind Treatment Period (DBTP) | Pregnancy | 1 | 0 | 0 |
| Double-blind Treatment Period (DBTP) | Randomized but not treated | 3 | 0 | 3 |
| Double-blind Treatment Period (DBTP) | Withdrawal by Subject | 9 | 6 | 5 |
| Safety Follow-up Period | Lost to Follow-up | 6 | 2 | 1 |
| Safety Follow-up Period | Withdrawal by Subject | 7 | 2 | 12 |
Baseline characteristics
| Characteristic | AMG334 70 mg | AMG334 140 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 37.3 years STANDARD_DEVIATION 10 | 37.1 years STANDARD_DEVIATION 9.6 | 38.0 years STANDARD_DEVIATION 10.1 | 37.5 years STANDARD_DEVIATION 9.9 |
| Monthly Migraine Days at Baseline | 8.09 Migraine days/month STANDARD_DEVIATION 2.62 | 8.27 Migraine days/month STANDARD_DEVIATION 3.14 | 8.35 Migraine days/month STANDARD_DEVIATION 2.76 | 8.23 Migraine days/month STANDARD_DEVIATION 2.81 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 participants | 0 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Asian | 278 participants | 184 participants | 269 participants | 731 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Multiple | 9 participants | 8 participants | 5 participants | 22 participants |
| Race/Ethnicity, Customized Other | 9 participants | 13 participants | 13 participants | 35 participants |
| Race/Ethnicity, Customized White | 58 participants | 35 participants | 60 participants | 153 participants |
| Sex: Female, Male Female | 272 Participants | 184 Participants | 281 Participants | 737 Participants |
| Sex: Female, Male Male | 66 Participants | 40 Participants | 57 Participants | 163 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 335 | 0 / 224 | 0 / 335 |
| other Total, other adverse events | 83 / 335 | 58 / 224 | 85 / 335 |
| serious Total, serious adverse events | 10 / 335 | 0 / 224 | 5 / 335 |
Outcome results
Primary
Change From Baseline in Monthly Migraine Days at the Last Month (Month 3) of the Double-blind Treatment Period (DBTP)
A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: 1. ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity 2. ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia
Time frame: Baseline up to Month 3
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AMG334 70 mg | Change From Baseline in Monthly Migraine Days at the Last Month (Month 3) of the Double-blind Treatment Period (DBTP) | -4.20 Migraine days/month | Standard Error 0.25 |
| AMG334 140 mg | Change From Baseline in Monthly Migraine Days at the Last Month (Month 3) of the Double-blind Treatment Period (DBTP) | -4.79 Migraine days/month | Standard Error 0.3 |
| Placebo | Change From Baseline in Monthly Migraine Days at the Last Month (Month 3) of the Double-blind Treatment Period (DBTP) | -3.10 Migraine days/month | Standard Error 0.25 |
p-value: 0.00295% CI: [-1.77, -0.42]Mixed Models Analysis
p-value: <0.00195% CI: [-2.45, -0.93]Mixed Models Analysis
Secondary
Change From Baseline in Acute Migraine-specific Medication Treatment Days at Month 3
Number of days on which acute migraine-specific medications were used were recorded in eDiary between each monthly IP dose. Migraine-Specific medications include two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications. Monthly migraine-specific medication use at baseline is the number of migraine-specific medication treatment days in the baseline period.
Time frame: Baseline up to Month 3
Population: Analysis set included participants with at least one acute migraine-specific medication use during baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AMG334 70 mg | Change From Baseline in Acute Migraine-specific Medication Treatment Days at Month 3 | -1.84 Migraine days/month | Standard Error 0.26 |
| AMG334 140 mg | Change From Baseline in Acute Migraine-specific Medication Treatment Days at Month 3 | -2.39 Migraine days/month | Standard Error 0.33 |
| Placebo | Change From Baseline in Acute Migraine-specific Medication Treatment Days at Month 3 | -0.49 Migraine days/month | Standard Error 0.26 |
p-value: <0.00195% CI: [-2.07, -0.64]Mixed Models Analysis
p-value: <0.00195% CI: [-2.71, -1.09]Mixed Models Analysis
Secondary
Change From Baseline in Headache Impact Scores as Measured by the Headache Impact Test (HIT-6) at Month 3
The HIT-6 is a short-form self-administered questionnaire based on the internet-HIT question pool. The HIT-6 was developed as a global measure of adverse headache impact to assess headache severity in the previous month and change in a patient's clinical status over a short period of time. Six items assess the frequency of pain severity, headaches limiting daily activity (household, work, school, and social). Each of the 6 questions is responded to using 1 of 5 response categories: never, rarely, sometimes, very often, or always. For each HIT-6 item, 6, 8, 10, 11, or 13 points, respectively, are assigned to the response provided. These points were summed to produce a total HIT-6 score that ranges from 36 to 78. Scores were categorized into 4 grades, representing little or no impact (49 or less), some impact (50-55), substantial impact (56-59), and severe impact (60-78) due to headache. Lower values represent better outcomes, therefore negative change denotes improveme
Time frame: Baseline up to Month 3
Population: Analysis included participants with a non-missing value at the corresponding time point of interest
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AMG334 70 mg | Change From Baseline in Headache Impact Scores as Measured by the Headache Impact Test (HIT-6) at Month 3 | -8.39 scores on a scale | Standard Error 0.45 |
| AMG334 140 mg | Change From Baseline in Headache Impact Scores as Measured by the Headache Impact Test (HIT-6) at Month 3 | -9.34 scores on a scale | Standard Error 0.54 |
| Placebo | Change From Baseline in Headache Impact Scores as Measured by the Headache Impact Test (HIT-6) at Month 3 | -6.62 scores on a scale | Standard Error 0.44 |
p-value: 0.00495% CI: [-2.99, -0.56]Mixed Models Analysis
p-value: <0.00195% CI: [-4.07, -1.36]Mixed Models Analysis
Secondary
Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Month 3
Achievement of at least a 50% reduction from baseline in monthly migraine days at Month 3. A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: 1. ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity 2. ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia
Time frame: Baseline and at Month 3
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AMG334 70 mg | Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Month 3 | 55.3 percentage of participants |
| AMG334 140 mg | Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Month 3 | 63.9 percentage of participants |
| Placebo | Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Month 3 | 44.8 percentage of participants |
p-value: 0.00795% CI: [1.12, 2.07]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [1.55, 3.15]Cochran-Mantel-Haenszel