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Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) Compared to Placebo in Migraine Prevention (ARISE)

Primary Purpose

Migraine

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Erenumab

Placebo

About this trial

This is an interventional treatment trial for Migraine focused on measuring Migraine, Headache, Episodic, Prevention, Prophylaxis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Erenumab

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Change From Baseline in Monthly Migraine Days at Week 12

Secondary Outcome Measures

Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Week 12

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

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

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

Number of Participants With Adverse Events

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

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.

Full Information

NCT ID

NCT02483585

First Posted

June 12, 2015

Last Updated

October 3, 2022

Sponsor

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT02483585

Brief Title

Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) Compared to Placebo in Migraine Prevention

Acronym

ARISE

Official Title

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Migraine Prevention

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Completed

Study Start Date

July 20, 2015 (Actual)

Primary Completion Date

July 11, 2016 (Actual)

Study Completion Date

March 20, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amgen

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Migraine

Keywords

Migraine, Headache, Episodic, Prevention, Prophylaxis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

577 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

Erenumab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Erenumab

Other Intervention Name(s)

AMG 334, Aimovig™

Intervention Description

Administered once a month by subcutaneous injection

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered once a month by subcutaneous injection

Primary Outcome Measure Information:

Title

Change From Baseline in Monthly Migraine Days at Week 12

Description

Time Frame