Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) Compared to Placebo in Migraine Prevention (ARISE)
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| ClinicalTrials.gov Identifier: NCT02483585 |
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Recruitment Status :
Completed
First Posted : June 29, 2015
Results First Posted : June 25, 2018
Last Update Posted : October 12, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Migraine | Drug: Erenumab Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 577 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Migraine Prevention |
| Actual Study Start Date : | July 20, 2015 |
| Actual Primary Completion Date : | July 11, 2016 |
| Actual Study Completion Date : | March 20, 2017 |
| Arm | Intervention/treatment |
|---|---|
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Placebo Comparator: Placebo
Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. At week 12 participants began treatment with erenumab 70 mg administered by subcutaneous injection at weeks 12, 16, 20, 24, 28, 32, and 36 in the open-label treatment phase.
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Drug: Placebo
Administered once a month by subcutaneous injection |
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Experimental: Erenumab
Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. Participants continued to receive erenumab 70 mg administered by subcutaneous injection at weeks 12, 16, 20, 24, 28, 32, and 36 in the open-label treatment phase.
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Drug: Erenumab
Administered once a month by subcutaneous injection
Other Names:
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- Change From Baseline in Monthly Migraine Days at Week 12 [ Time Frame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase ]
A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine with or without aura.
The change from baseline in monthly migraine days was calculated as the number of migraine days during the last 4 weeks of the 12-week double-blind treatment phase - the number of migraine days during the 4-week baseline phase.
- Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Week 12 [ Time Frame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase ]
A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine without aura or a migraine with aura. Monthly migraine days were calculated as the number of migraine days in the 4-week baseline phase and during the last 4 weeks of double-blind treatment.
At least a 50% reduction from baseline in monthly migraine days was determined if the change in monthly migraine days from the 4-week baseline phase to the last 4 weeks of the 12-week double-blind treatment phase * 100 / baseline monthly migraine days was less than or equal to -50%.
- Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days at Week 12 [ Time Frame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase ]
Monthly acute migraine-specific medication treatment days is the number of days on which migraine specific medications were used between monthly doses of study drug. Migraine-specific medications includes two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications.
The change from baseline in monthly acute migraine-specific treatment days was calculated as the number of migraine-specific treatment days during the last 4 weeks of the 12-week double-blind treatment phase - the number of migraine-specific treatment days during the 4-week baseline phase.
- Percentage of Participants With at Least a 5-point Reduction From Baseline in Average Impact on Everyday Activities Domain Score Measured by MPFID at Week 12 [ Time Frame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase ]
The Migraine Physical Function Impact Diary (MPFID) is a self-administered 13-item instrument measuring physical functioning. It has two domains, Impact on Everyday Activities (7 items) and Physical Impairment (5 items), and one stand-alone global question. Participants completed the MPFID daily in an electronic diary based on the past 24 hours. Participants responded to each item on a 5-point scale, with difficulty items ranging from "Without any difficulty" (1) to "Unable to do" (5) and frequency items ranging from "None of the time" (1) to "All of the time" (5). For each domain, the scores were calculated as the sum of the responses and rescaled to 0 - 100, with higher scores representing greater impact of migraine.
Achievement of at least a 5 point reduction from baseline in the monthly average domain score was calculated as (monthly average domain score during the last 4 weeks of the 12-week double-blind treatment phase - baseline monthly average domain score) was ≤ -5.
- Percentage of Participants With at Least a 5-Point Reduction From Baseline in Average Impact on Physical Impairment Domain Score Measured by MPFID at Week 12 [ Time Frame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase ]
The Migraine Physical Function Impact Diary (MPFID) is a self-administered 13-item instrument measuring physical functioning. It has two domains, Impact on Everyday Activities (7 items) and Physical Impairment (5 items), and one stand-alone global question. Participants completed the MPFID daily in an electronic diary based on the past 24 hours. Participants responded to each item on a 5-point scale, with difficulty items ranging from "Without any difficulty" (1) to "Unable to do" (5) and frequency items ranging from "None of the time" (1) to "All of the time" (5). For each domain, the scores were calculated as the sum of the responses and rescaled to 0 - 100, with higher scores representing greater impact of migraine.
Achievement of at least a 5 point reduction from baseline in the monthly average domain score was calculated as (monthly average domain score during the last 4 weeks of the 12-week double-blind treatment phase - baseline monthly average domain score) was ≤ -5.
- Number of Participants With Adverse Events [ Time Frame: From first dose of study drug up to 12 weeks after the last dose. The double-blind treatment phase was 12 weeks and the open-label treatment phase was 28 weeks. ]
Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4, where:
Grade 1 = Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2 = Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL; Grade 4 = Life-threatening consequences; urgent intervention indicated Grade 5 = Death related to AE.
- Number of Participants Who Developed Antibodies to Erenumab [ Time Frame: Baseline (the period prior to the first dose erenumab 70 mg) and post-baseline (the period after the first dose of erenumab 70 mg until 12 weeks after last dose, up to 48 weeks total) ]
Blood samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect anti-drug antibodies (ADA) against erenumab. Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based bioassay to determine neutralizing activity against erenumab (Neutralizing Antibody Assay).
Developing antibody incidence indicates participants with a negative or no result at baseline and a positive result at any time post-baseline.
If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies.
Transient indicates a negative result at the participant's last time point tested, for those participants with a positive binding/neutralizing result post-baseline.
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| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- History of migraines (with or without aura) for ≥ 12 months
- Migraine frequency: ≥ 4 and < 15 migraine days per month on average acrossthe 3 months prior to screening
- Headache (ie, migraine and non-migraine headache) frequency: < 15 headache days per month on average across the 3 months prior to screening
- Demonstrated compliance with the eDiary
Exclusion Criteria:
- Older than 50 years of age at migraine onset.
- History of cluster headache or hemiplegic migraine headache.
- Unable to differentiate migraine from other headaches
- No therapeutic response with > 2 categories for prophylactic treatment of migraine after an adequate therapeutic trial.
- Concomitant use of 2 or more medications with possible migraine prophylactic effects within 2 months prior to the start of the baseline phase or during the baseline phase. If only 1 prophylactic medication is used, the dose must be stable within 2 months prior to the start of the baseline phase and throughout the study
- Used a prohibited medication, device, or procedure within 2 months prior to the start of the baseline phase or during the baseline phase.
- Received botulinum toxin
- Anticipated to require any excluded medication, device, or procedure during the study.
- Active chronic pain syndromes (such as fibromyalgia and chronic pelvic pain).
- History of major psychiatric disorder.
- History of seizure disorder or other significant neurological conditions other than migraine.
- Human immunodeficiency virus (HIV) infection by history.
- Myocardial infarction (MI), stroke, transient ischemic attack (TIA), unstable angina, or coronary artery bypass surgery or other revascularization procedure within 12 months prior to screening.
- The subject is at risk of self-harm or harm to others. Previously randomized into an AMG 334 study.
- Unlikely to be able to complete all protocol required study visits or procedures, and/or to comply with all required study procedures.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02483585
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| Study Director: | MD | Amgen |
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Amgen |
| ClinicalTrials.gov Identifier: | NCT02483585 |
| Other Study ID Numbers: |
20120297 2014-004463-20 ( EudraCT Number ) |
| First Posted: | June 29, 2015 Key Record Dates |
| Results First Posted: | June 25, 2018 |
| Last Update Posted: | October 12, 2022 |
| Last Verified: | October 2022 |
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Migraine Headache Episodic Prevention Prophylaxis |
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Migraine Disorders Headache Disorders, Primary Headache Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Erenumab |
Calcitonin Gene-Related Peptide Receptor Antagonists Molecular Mechanisms of Pharmacological Action Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs |