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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
Recruitment Status : Completed
First Posted : June 29, 2015
Results First Posted : June 25, 2018
Last Update Posted : November 29, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
To evaluate the effect of erenumab compared to placebo on the change from baseline in monthly migraine days, in adults with episodic migraine.

Condition or disease Intervention/treatment Phase
Migraine Drug: Erenumab Drug: Placebo Phase 3

Detailed Description:
Adults with a history of migraine with or without aura for ≥ 12 months and who experience ≥ 4 to < 15 migraine days per month with < 15 headache days per month will be randomized 1:1 to placebo or erenumab. Double-blind erenumab or placebo will be administered during the 12-week double-blind treatment phase and open-label erenumab will be administered during the 28-week open-label treatment phase.

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 19, 2015
Actual Primary Completion Date : July 11, 2016
Actual Study Completion Date : March 20, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Migraine

Arm Intervention/treatment
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.
Drug: Placebo
Administered once a month by subcutaneous injection

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.
Drug: Erenumab
Administered once a month by subcutaneous injection
Other Names:
  • AMG 334
  • Aimovig™




Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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%.


  2. 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.


  3. 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.


  4. 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.


  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.


  6. 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.




Information from the National Library of Medicine

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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
Criteria

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.

Information from the National Library of Medicine

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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Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen

Additional Information:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02483585     History of Changes
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: November 29, 2018
Last Verified: November 2018

Keywords provided by Amgen:
Migraine
Headache
Episodic
Prevention
Prophylaxis

Additional relevant MeSH terms:
Migraine Disorders
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases