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A Safety and Efficacy Study to Evaluate AMG 334 in Migraine Prevention

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02630459
Recruitment Status : Active, not recruiting
First Posted : December 15, 2015
Results First Posted : March 13, 2019
Last Update Posted : March 13, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
Randomized, double-blind, placebo-controlled, parallel-group, multicenter study followed by an open-label treatment phase. To evaluate the effect of erenumab (AMG 334) compared to placebo on the change from baseline in monthly migraine days.

Condition or disease Intervention/treatment Phase
Migraine Drug: Placebo Drug: Erenumab Phase 2

Detailed Description:
This is a Phase 2, randomized, double-blind, placebo-controlled study in subjects with episodic migraine. The study is designed to evaluate if treatment with erenumab once a month for 6 months compared with placebo is effective in reducing the mean monthly migraine days. Additionally, this study will continue to evaluate the efficacy and safety of erenumab during the open label treatment phase where subjects will continue to receive active treatment monthly.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 475 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Migraine Prevention
Actual Study Start Date : January 6, 2016
Actual Primary Completion Date : September 25, 2017
Estimated Study Completion Date : June 3, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Migraine

Arm Intervention/treatment
Placebo Comparator: Placebo
Participants received placebo by subcutaneous injection on day 1 and atweeks 4, 8, 12, 16, and 20 in the double-blind treatment phase.
Drug: Placebo
Placebo Comparator

Experimental: Erenumab 28 mg QM
Participants received erenumab 28 mg by subcutaneous injection on day 1 and at weeks 4, 8, 12, 16, and 20 in the double-blind treatment phase.
Drug: Erenumab
Investigational Product was dosed once monthly (QM) by subcutaneous injections at day 1 and weeks 4, 8, 12, 16, and 20.
Other Name: AMG 334, Aimovig™

Experimental: Erenumab 70 mg QM
Participants received erenumab 70 mg by subcutaneous injection on day 1 and at weeks 4, 8, 12, 16, and 20 in the double-blind treatment phase.
Drug: Erenumab
Investigational Product was dosed once monthly (QM) by subcutaneous injections at day 1 and weeks 4, 8, 12, 16, and 20.
Other Name: AMG 334, Aimovig™

Experimental: Erenumab 140 mg QM
Participants received erenumab 140 mg by subcutaneous injection on day 1 and at weeks 4, 8, 12, 16, and 20 in the double-blind treatment phase.
Drug: Erenumab
Investigational Product was dosed once monthly (QM) by subcutaneous injections at day 1 and weeks 4, 8, 12, 16, and 20.
Other Name: AMG 334, Aimovig™




Primary Outcome Measures :
  1. Change From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6 [ Time Frame: 4-week baseline phase and months 4, 5 and 6 of double-blind treatment phase. ]
    A migraine day was defined as 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 a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: a) ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe, exacerbated with exercise/physical activity; b) ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia. Change from baseline was calculated using the mean monthly migraine days from months 4, 5 and 6 of the double-blind treatment phase minus the number of migraine days during the 4-week baseline phase. Least squares (LS) mean was estimated using a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (current, prior only, or no prior/current treatment), and baseline value as covariates.


Secondary Outcome Measures :
  1. Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6 [ Time Frame: 4-week baseline phase and months 4, 5 and 6 of double-blind treatment phase. ]

    A migraine day was defined as 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 a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: a) ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe, exacerbated with exercise/physical activity; b) ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia.

    At least a 50% reduction from baseline in monthly migraine days was determined if; (mean monthly migraine days over the last three months of the double-blind treatment phase minus baseline monthly migraine days) * 100 / baseline monthly migraine days, was less than or equal to -50%.


  2. Change From Baseline in Mean Monthly Acute Migraine-Specific Medication Treatment Days at Months 4, 5 and 6 [ Time Frame: 4-week baseline phase and months 4, 5 and 6 of double-blind treatment phase. ]

    An acute migraine-specific medication treatment day was defined as any calendar day during which the participant took a migraine-specific medication (ie, triptan or ergotamine-derivatives).

    The change from baseline was calculated using the mean monthly acute migraine-specific medication treatment days over the last three months (months 4, 5 and 6) of the double-blind treatment phase minus the baseline monthly acute migraine-specific medication treatment days.

    LS mean was estimated using a generalized linear mixed model which included treatment, visit, treatment by visit interaction, stratification factor (prior/current treatment), and baseline value as covariates.




Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria to be assessed prior to entering the subject into the initial screening and/or baseline phase:

  • Provided informed consent prior to initiation of any study-specific activities/procedures
  • History of migraine (with or without aura) for ≥ 12 months prior to screening according to the International Headache Society (IHS) Classification The International Classification of Headache Disorders (ICHD)-3 (Headache Classification Committee of the IHS, 2013),
  • Migraine frequency: ≥ 4 and < 15 migraine days per month on average across the 3 months prior to screening,
  • Headache frequency: < 15 headache days per month on average across the 3 months prior to screening.

Inclusion Criteria to be assessed during the baseline phase and confirmed prior to randomizing the subject into the double-blind treatment phase:

  • Demonstrated at least 80% compliance with the electronic Diary (eDiary),
  • Migraine frequency: ≥ 4 and < 15 migraine days during the baseline phase based on the eDiary calculations,
  • Headache frequency: < 15 headache days during the baseline phase based on the eDiary calculations.

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 of the following 7 medication categories for prophylactic treatment of migraine after an adequate therapeutic trial: Category 1: Divalproex sodium, sodium valproate, Category 2: Topiramate, Category 3: Beta blockers (for example: atenolol, bisoprolol, metoprolol, nadolol, nebivolol, pindolol, propranolol, timolol), Category 4: Tricyclic antidepressants (for example: amitriptyline, nortriptyline, protriptyline),Category 5: Serotonin-norepinephrine reuptake inhibitors (for example: venlafaxine, desvenlafaxine, duloxetine, milnacipran), Category 6: Flunarizine, verapamil, lomerizine, Category 7: Lisinopril, candesartan,
  • 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 in the head and/or neck region within 4 months prior to the start of the baseline phase or during the baseline phase,
  • Taken the following for any indication in any month during the 2 months prior to the start of the baseline phase: Ergotamines or triptans on ≥ 10 days per month, or Simple analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs], acetaminophen) on ≥ 15 days per month, or Opioid- or butalbital-containing analgesics on ≥ 4 days per month,
  • 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 (such as schizophrenia and bipolar disorder), or current evidence of depression based on a Beck Depression Inventory (BDI)-II total score > 19 at screening. Subjects with anxiety disorder and/or major depressive disorder are permitted in the study if they are considered by the investigator to be stable and are taking no more than 1 medication for each disorder. Subjects must have been on a stable dose within the 3 months prior to the start of the baseline phase,
  • History of seizure disorder or other significant neurological conditions other than migraine. Note: A single childhood febrile seizure is not exclusionary,
  • Malignancy within the 5 years prior to screening, except non melanoma skin cancers, cervical or breast ductal carcinoma in situ,
  • Human immunodeficiency virus (HIV) infection by history,
  • Hepatic disease by history, or total bilirubin (TBL) ≥ 2.0 x upper limit of normal (ULN) or alanine transaminase (ALT) or aspartate aminotransferase (AST) ≥ 3.0 x ULN, as assessed by the central laboratory at initial screening, or evidence of acute or chronic hepatitis B or hepatitis C virus. Hepatitis status will be evaluated by testing for hepatitis B surface antigen (HepBsAg), total hepatitis B core antibody (HepBcAb) and hepatitis C antibody by the central laboratory at initial screening. Polymerase chain reaction (PCR) should be performed to confirm active disease only if total HepBcAb is positive and HepBsAg is negative or if C antibody is positive,
  • Myocardial infarction, stroke, transient ischemic attack (TIA), unstable angina, or coronary artery bypass surgery or other revascularization procedure within 12 months prior to screening,
  • History or evidence of any other unstable or clinically significant medical condition that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion,
  • Subject has any clinically significant vital sign, laboratory, or electrocardiogram (ECG) abnormality during screening that, in the opinion of the investigator, could pose a risk to subject safety or interfere with the study evaluation,
  • The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior or endorsing items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) assessed at screening,
  • Evidence of drug or alcohol abuse or dependence within 12 months prior to screening, based on medical records, patient self-report, or positive urine drug test performed during screening (with the exception of prescribed medications such as opioids or barbiturates),
  • Pregnant or breastfeeding, or is a female expecting to conceive during the study, including through 16 weeks after the last dose of investigational product,
  • Female subject of childbearing potential who is unwilling to use an acceptable method of effective contraception during treatment with investigational product through 16 weeks after the last dose of investigational product,
  • Currently receiving treatment in another investigational device or drug study, or less than 90 days prior to screening since ending treatment on another investigational device or drug study(-ies),
  • Known sensitivity to any component of the investigational product (Refer to the Investigational Product Instruction Manual [IPIM] for details),
  • Previously randomized into an erenumab study,
  • Member of investigational site staff or relative of the investigator,
  • Unlikely to be able to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, independent completion of eDiary items) to the best of the subject's and investigator's knowledge.

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): NCT02630459


Locations
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Japan
Research Site
Kamogawa-shi, Chiba, Japan, 296-0041
Research Site
Saijo-shi, Ehime, Japan, 793-0030
Research Site
Ota-shi, Gunma, Japan, 373-8585
Research Site
Hiroshima-shi, Hiroshima, Japan, 730-8518
Research Site
Sapporo-shi, Hokkaido, Japan, 060-0004
Research Site
Sapporo-shi, Hokkaido, Japan, 060-8570
Research Site
Sapporo-shi, Hokkaido, Japan, 063-0005
Research Site
Kobe-shi, Hyogo, Japan, 658-0064
Research Site
Tsukuba-shi, Ibaraki, Japan, 305-8576
Research Site
Kahoku-gun, Ishikawa, Japan, 929-0342
Research Site
Morioka-shi, Iwate, Japan, 020-8505
Research Site
Kagoshima-shi, Kagoshima, Japan, 892-0844
Research Site
Kawasaki-shi, Kanagawa, Japan, 211-8533
Research Site
Kawasaki-shi, Kanagawa, Japan, 211-8588
Research Site
Kawasaki-shi, Kanagawa, Japan, 216-8511
Research Site
Kumamoto-shi, Kumamoto, Japan, 861-2101
Research Site
Kumamoto-shi, Kumamoto, Japan, 862-8505
Research Site
Kyoto-shi, Kyoto, Japan, 600-8811
Research Site
Sendai-shi, Miyagi, Japan, 982-0014
Research Site
Osaka-shi, Osaka, Japan, 556-0017
Research Site
Osakasayama-shi, Osaka, Japan, 589-8511
Research Site
Toyonaka-shi, Osaka, Japan, 560-0012
Research Site
Saga-shi, Saga, Japan, 840-0806
Research Site
Iruma-gun, Saitama, Japan, 350-0495
Research Site
Saitama-shi, Saitama, Japan, 338-8577
Research Site
Tokorozawa-shi, Saitama, Japan, 359-1141
Research Site
Shizuoka-shi, Shizuoka, Japan, 420-0853
Research Site
Shimotsuga-gun, Tochigi, Japan, 321-0293
Research Site
Bunkyo-ku, Tokyo, Japan, 113-8431
Research Site
Bunkyo-ku, Tokyo, Japan, 113-8603
Research Site
Chofu-shi, Tokyo, Japan, 182-0006
Research Site
Chuo-ku, Tokyo, Japan, 104-8560
Research Site
Hachioji-shi, Tokyo, Japan, 192-0032
Research Site
Minato-ku, Tokyo, Japan, 106-6106
Research Site
Minato-ku, Tokyo, Japan, 108-8642
Research Site
Shibuya-ku, Tokyo, Japan, 151-0051
Research Site
Shinjuku-ku, Tokyo, Japan, 160-0017
Research Site
Shinjuku-ku, Tokyo, Japan, 160-8582
Research Site
Yonago-city, Tottori, Japan, 683-8504
Research Site
Toyama-shi, Toyama, Japan, 930-0194
Research Site
Toyama-shi, Toyama, Japan, 930-0803
Research Site
Hofu-shi, Yamaguchi, Japan, 747-0802
Research Site
Yamaguchi-shi, Yamaguchi, Japan, 754-0002
Research Site
Kai-shi, Yamanashi, Japan, 400-0124
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
  Study Documents (Full-Text)

Documents provided by Amgen:
Study Protocol  [PDF] June 5, 2017
Statistical Analysis Plan  [PDF] February 14, 2016


Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02630459     History of Changes
Other Study ID Numbers: 20120309
First Posted: December 15, 2015    Key Record Dates
Results First Posted: March 13, 2019
Last Update Posted: March 13, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Amgen:
Migraine Prevention
Headache
Prophylaxis

Additional relevant MeSH terms:
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Migraine Disorders
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Erenumab
Antibodies, Monoclonal
Calcitonin Gene-Related Peptide Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Immunologic Factors