MigrainePhase 2NCT02630459

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

A Phase 2 study testing Erenumab in people with Migraine, run by Amgen at 44 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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

Who is it for?: Ages 20 to 65 years
Conditions the study is for: Migraine
What is being tested?: Erenumab
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 475 participants
Where: 44 sitesJapan
Study dates: 6 Jan 2016to 5 Jun 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

None listed.

Who cannot join

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,

Show all 27Show fewer

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.
Unreliability as a study participant based on the investigator's (or designee's) knowledge of the subject (eg, unwillingness to adhere to the protocol, unwilling to self-inject using an autoinjector (AI)/pen after review of the Instructions for Use). Subjects receiving erenumab 70 mg in the open-label phase are not eligible.

Trial locations and contacts

44 sites in 1 country.

City, postcode or hospital

44 sites in 1 country

Japan44 sites

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

Other trials in Japan

About this study

Official title: A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Migraine Prevention

Read the detailed description

This is a Phase 2, randomized, double-blind, placebo-controlled study in participants with episodic migraine. The study's double blind treatment phase (DBTP) 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 OLTP where participants will continue to receive active treatment monthly.

The study also includes a clinical home use (CHU) sub-study to assess a participant's ability to self-administer 140 mg of erenumab. Participants will be randomized 1:1 to use either 2 pre-filled 70 mg/mL autoinjector (AI)/pens or 1 pre-filled 140 mg/mL AI/pen. Participation in the substudy is optional, and no additional samples will be collected for the sub-study.

After implementation of Protocol Amendment 2, the dose of erenumab in the OLTP increased from 70 mg to 140 mg QM. Participants who had already completed week 48 remain on 70 mg QM, participants not yet starting the OLTP, or not yet completing the week 48 visit receive erenumab 140 mg QM for the remainder of the OLTP.

Conditions: Migraine
Being tested: Placebo, Erenumab
Keywords: Migraine Prevention, Headache, Prophylaxis
Medical subject headings: Migraine Disorders, Headache

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
placebo via subcutaneous injection
ErenumabDrug
Also called AMG 334, Aimovig™
erenumab via subcutaneous injection
ErenumabDrug
Also called AMG 334, Aimovig™
erenumab via autoinjector (AI)/pen

Study groups in NCT02630459
Study group	Role	What they receive
Double Blind Treatment Phase (DBTP): Placebo	Placebo comparator	Participants received placebo by subcutaneous injection on day 1 and at weeks 4, 8, 12, 16, and 20 in the double-blind treatment phase. Receives: Drug: Placebo
DBTP: Erenumab 28 mg QM	Experimental	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. Receives: Drug: Erenumab
DBTP: Erenumab 70 mg QM	Experimental	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. Receives: Drug: Erenumab
DBTP: Erenumab 140 mg QM	Experimental	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. Receives: Drug: Erenumab
Open-Label Treatment Phase (OLTP): Erenumab 70-140 mg QM	Experimental	Participants received an erenumab dose of 70 and/or 140 mg QM SC (depending on the participant's visit completion status after Institutional Review Board [IRB] approval of Protocol Amendment 2) in the OLTP for a total of 76 weeks. Receives: Drug: Erenumab
CHU Sub-Study: Two 70 mg/mL AI/pens	Experimental	A subset of participants in the OLTP randomized to self administer erenumab via two 70 mg/mL autoinjector (AI)/pens on day 29 and day 57 of the CHU Sub-Study Receives: Drug: Erenumab
CHU Sub-Study: One 140 mg/mL AI/pen	Experimental	A subset of participants in the OLTP randomized to self administer erenumab via one 140 mg/mL AI/pen on day 29 and day 57 of the CHU Sub-Study Receives: Drug: Erenumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6
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 DBTP 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.
Measured: 4-week baseline phase and months 4, 5 and 6 of DBTP.
CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8)
On CHU day 29 and day 57, site staff interviewed sub-study participants and asked if they administered a full, partial, or no dose of erenumab (after explaining that a full dose means that the entire volume of the AI/pen was injected) and documented the participant's response in the electronic case report form. Data presented are the percentage of participants who reported "full administration," "not full administration," or "discontinued investigational product (ie, no dose)." (Day 1 of the CHU substudy occurred at any OLTP study visit [up to week 88] as long as the participant had previously received at least 1 OL dose of erenumab 140 mg.)
Measured: CHU day 29 (week 4) and day 57 (week 8)

Secondary outcomes (10)

Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days at Months 4, 5 and 6
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 DBTP minus baseline monthly migraine days) * 100 / baseline monthly migraine days, was less than or equal to -50%.
Measured: 4-week baseline phase and months 4, 5 and 6 of DBTP.
Change From Baseline in Mean Monthly Acute Migraine-Specific Medication Treatment Days at Months 4, 5 and 6
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 DBTP 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.
Measured: 4-week baseline phase and months 4, 5 and 6 of DBTP.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. A serious adverse event (SAE) is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening, grade 5=death).
Measured: From first dose of IP up to week 24
Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP
An AE is defined as any untoward medical occurrence in a clinical trial participant. An SAE is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Events were graded according to the NCI CTCAE version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening, grade 5=death).
Measured: From first dose of IP in the OLTP (week 24) through the end of the OLTP (week 100) plus 12 weeks
Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study
An AE is defined as any untoward medical occurrence in a clinical trial participant. An SAE is defined as an adverse event that meets at least 1 of the following serious criteria: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Events were graded according to the NCI CTCAE version 4.03 (grade 1=mild, grade 2=moderate, grade 3=severe, grade 4= life-threatening, grade 5=death). TEAEs leading to discontinuation of IP are TEAEs leading to complete discontinuation of erenumab regardless of CHU IP or parent study IP.
Measured: CHU sub-study day 1 through day 85 (end of CHU sub-study). Day 1 of the CHU substudy occurred at any OLTP study visit (up to week 88) as long as the participant had previously received at least 1 OL dose of erenumab 140 mg.
Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP
Post-baseline is defined as any assessment done after the first dose of IP. Liver Function tests included alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBL). ULN=upper limit of normal.
Measured: From the first dose of study IP through the end of the DBTP (up to week 24)
Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP
Post-baseline is defined as any assessment done after the first dose of OLTP IP. Liver Function tests included alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBL). ULN=upper limit of normal.
Measured: From the first dose of OLTP IP (week 24) through the end of the OLTP (up to week 100)
Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP
Participants with increases (↑) from baseline (BL) in diastolic blood pressure (DBP) and systolic blood pressure (SBP) at week 24 (Wk24) are presented.
Measured: Baseline (last assessment prior to first dose of IP), week 24
Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP
Participants with increases (↑) from baseline (BL) in diastolic blood pressure (DBP) and systolic blood pressure (SBP) at week 100 (Wk100) are presented.
Measured: Pre-OLTP Baseline (last assessment prior to first dose of IP in OLTP), week 100
Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab
Data are summarized by the treatment participants received during the double-blind treatment phase. Placebo participants may have received erenumab 70 mg or 140 mg during the OLTP. Baseline is defined as the last antibody assessment on or prior to the first dose of erenumab.
Transient binding/neutralizing antibody responses are defined as a negative (neg) result at the participant's last timepoint tested among participants who developed binding/neutralizing antibodies post-baseline.
Measured: Baseline (first dose of erenumab) up to end of study (week 100) plus 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Jan 20165 Jun 2019

First posted15 Dec 2015 (estimated)
Study start6 Jan 2016
Primary completion25 Sep 2017
Study completion5 Jun 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for MigraineStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 475 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02630459
Sponsor's protocol ID: 20120309
Status last verified: Oct 2022
First submitted: 11 Dec 2015
Last updated: 12 Oct 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Publications

Sakai F, Takeshima T, Tatsuoka Y, Hirata K, Lenz R, Wang Y, Cheng S, Hirama T, Mikol DD. A Randomized Phase 2 Study of Erenumab for the Prevention of Episodic Migraine in Japanese Adults. Headache. 2019 Nov;59(10):1731-1742. doi: 10.1111/head.13652. Epub 2019 Oct 14.
PubMed 31612482
Zhou Y, Zhang F, Starcevic Manning M, Hu Z, Hsu CP, Chen PW, Peng C, Loop B, Mytych DT, Paiva da Silva Lima G. Immunogenicity of erenumab: A pooled analysis of six placebo-controlled trials with long-term extensions. Cephalalgia. 2022 Jul;42(8):749-760. doi: 10.1177/03331024221075621. Epub 2022 Mar 10.
PubMed 35272533
Hiramatsu K, Onizuka Y, Hasebe M, Yoshida R, Numachi Y. Novel Drug for Migraine Prophylaxis: Mode of Action, Efficacy and Safety of Erenumab. Shinryo to Shinyaku (Med Cons New-Remed) 2021:58(11):797-832
Sakai F, Takeshima T, Tatsuoka Y, Hirata K, Cheng S, Numachi Y, Peng C, Xue F, Mikol DD. Long-term efficacy and safety during open-label erenumab treatment in Japanese patients with episodic migraine. Headache. 2021 Apr;61(4):653-661. doi: 10.1111/head.14096. Epub 2021 Mar 25.
PubMed 33764538

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Migraine trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Migraine Prevention
ClinicalTrials.gov ID: NCT02630459
Acronym / sponsor ID: 20120309
Conditions: Migraine
Keywords: Migraine Prevention, Headache, Prophylaxis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 475 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: 6 Jan 2016 (actual)
Primary completion: 25 Sep 2017 (actual)
Study completion: 5 Jun 2019 (actual)
First posted: 15 Dec 2015 (estimated)
Results: Posted 13 Mar 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 7

Arm	Type	Receives
Double Blind Treatment Phase (DBTP): Placebo	Placebo comparator	Drug: PlaceboParticipants received placebo by subcutaneous injection on day 1 and at weeks 4, 8, 12, 16, and 20 in the double-blind treatment phase.
DBTP: Erenumab 28 mg QM	Experimental	Drug: ErenumabParticipants 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.
DBTP: Erenumab 70 mg QM	Experimental	Drug: ErenumabParticipants 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.
DBTP: Erenumab 140 mg QM	Experimental	Drug: ErenumabParticipants 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.
Open-Label Treatment Phase (OLTP): Erenumab 70-140 mg QM	Experimental	Drug: ErenumabParticipants received an erenumab dose of 70 and/or 140 mg QM SC (depending on the participant's visit completion status after Institutional Review Board [IRB] approval of Protocol Amendment 2) in the OLTP for a total of 76 weeks.
CHU Sub-Study: Two 70 mg/mL AI/pens	Experimental	Drug: ErenumabA subset of participants in the OLTP randomized to self administer erenumab via two 70 mg/mL autoinjector (AI)/pens on day 29 and day 57 of the CHU Sub-Study
CHU Sub-Study: One 140 mg/mL AI/pen	Experimental	Drug: ErenumabA subset of participants in the OLTP randomized to self administer erenumab via one 140 mg/mL AI/pen on day 29 and day 57 of the CHU Sub-Study

Who may qualify

Ages: 20 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (0 listed)

Key exclusion criteria (27 listed)

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,

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Placeboplacebo via subcutaneous injection	Drug	Double Blind Treatment Phase (DBTP): Placebo
ErenumabAlso: AMG 334, Aimovig™erenumab via subcutaneous injection	Drug	DBTP: Erenumab 140 mg QM, DBTP: Erenumab 28 mg QM, DBTP: Erenumab 70 mg QM, Open-Label Treatment Phase (OLTP): Erenumab 70-140 mg QM
ErenumabAlso: AMG 334, Aimovig™erenumab via autoinjector (AI)/pen	Drug	CHU Sub-Study: One 140 mg/mL AI/pen, CHU Sub-Study: Two 70 mg/mL AI/pens

Primary outcome

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 DBTP.
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 DBTP 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.
CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8)
Time frame: CHU day 29 (week 4) and day 57 (week 8)
On CHU day 29 and day 57, site staff interviewed sub-study participants and asked if they administered a full, partial, or no dose of erenumab (after explaining that a full dose means that the entire volume of the AI/pen was injected) and documented the participant's response in the electronic case report form. Data presented are the percentage of participants who reported "full administration," "not full administration," or "discontinued investigational product (ie, no dose)." (Day 1 of the CHU substudy occurred at any OLTP study visit [up to week 88] as long as the participant had previously received at least 1 OL dose of erenumab 140 mg.)

10 secondary outcomes

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 DBTP.
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 DBTP.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the DBTP
Time frame: From first dose of IP up to week 24
Number of Participants With TEAEs, Serious TEAEs, Discontinuations Due to TEAEs, and Fatal TEAEs During the OLTP
Time frame: From first dose of IP in the OLTP (week 24) through the end of the OLTP (week 100) plus 12 weeks
Number of Participants With TEAEs, Serious TEAEs, Discotninuations Due to TEAEs, Fatal TEAEs, and Adverse Device Effects During the CHU Sub-Study
Time frame: CHU sub-study day 1 through day 85 (end of CHU sub-study). Day 1 of the CHU substudy occurred at any OLTP study visit (up to week 88) as long as the participant had previously received at least 1 OL dose of erenumab 140 mg.
Number of Participants With Post-Baseline Liver Function Test Abnormalities During the DBTP
Time frame: From the first dose of study IP through the end of the DBTP (up to week 24)
Number of Participants With Post-Baseline Liver Function Test Abnormalities During the OLTP
Time frame: From the first dose of OLTP IP (week 24) through the end of the OLTP (up to week 100)
Number of Participants With Blood Pressure Changes From Baseline in Categories at Week 24 During the DBTP
Time frame: Baseline (last assessment prior to first dose of IP), week 24
Number of Participants With Blood Pressure Changes From Pre-OLTP Baseline in Categories at Week 100 During the OLTP
Time frame: Pre-OLTP Baseline (last assessment prior to first dose of IP in OLTP), week 100
Number of Participants With Anti-Erenumab Antibodies During the Entire Study for Participants Who Received ≥ 1 Dose of Erenumab
Time frame: Baseline (first dose of erenumab) up to end of study (week 100) plus 12 weeks

Results and safety

Results posted to the registry on 13 Mar 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
DBTP: Placebo	136	133
DBTP: Erenumab 28 mg QM	67	65
DPTP: Erenumab 70 mg QM	135	130
DBTP: Erenumab 140 mg QM	137	134
OLTP: Erenumab 70 mg QM (Initial OL Dose)	0	0
OLTP: Erenumab 140 mg QM (Initial OL Dose)	0	0
CHU Sub-Study: Two 70 mg/mL AI/Pens	0	0
CHU Sub-Study: One 140 mg/mL AI/Pen	0	0

Primary outcome: 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 DBTP.. Least squares mean (95% Confidence Interval). Unit: Days

Measure	DBTP: Placebo n = 136	DBTP: Erenumab 28 mg QM n = 66	DPTP: Erenumab 70 mg QM n = 135	DBTP: Erenumab 140 mg QM n = 136
Value	0.06 (-0.46 to 0.58)	-1.19 (-1.91 to -0.47)	-2.25 (-2.78 to -1.73)	-1.83 (-2.35 to -1.31)

DBTP: Placebo vs DBTP: Erenumab 140 mg QM: LS Mean Difference: -1.89 (95% CI -2.58 to -1.20), p <0.001, Generalized Linear Mixed Model
DBTP: Placebo vs DPTP: Erenumab 70 mg QM: LS Mean Difference: -2.31 (95% CI -3.00 to -1.62), p <0.001, Generalized Linear Mixed Model
DBTP: Placebo vs DBTP: Erenumab 28 mg QM: LS Mean Difference: -1.25 (95% CI -2.10 to -0.41), p = 0.004, Generalized Linear Mixed Model

Population analysed: Efficacy Analysis Set: Participants who received at least 1 dose of the investigational product (IP) and had at least 1 change from baseline measurement in monthly migraine days during the DBTP.

Primary outcome: CHU Sub-Study: Participant-Reported Outcome of Attempted Full-Dose Administration at Day 29 (Week 4) and Day 57 (Week 8)

Time frame: CHU day 29 (week 4) and day 57 (week 8). Number (95% Confidence Interval). Unit: percentage of participants

Measure	CHU Sub-Study: Two 70 mg/mL AI/Pens n = 24	CHU Sub-Study: One 140 mg/mL AI/Pen n = 25
Week 4: Full Administration	100.0 (86.2 to 100.0)	100.0 (86.7 to 100.0)
Week 4: Not Full Administration	0.0 (0.0 to 13.8)	0.0 (0.0 to 13.3)
Week 4: Discontinued Investigational Product	0.0 (0.0 to 13.8)	0.0 (0.0 to 13.3)
Week 8: Full Administration	100.0 (86.2 to 100.0)	100.0 (86.7 to 100.0)
Week 8: Not Full Administration	0.0 (0.0 to 13.8)	0.0 (0.0 to 13.3)
Week 8: Discontinued Investigational Product	0.0 (0.0 to 13.8)	0.0 (0.0 to 13.3)

CHU Sub-Study: Two 70 mg/mL AI/Pens vs CHU Sub-Study: One 140 mg/mL AI/Pen: Treatment Difference: 0.0 (95% CI -13.3 to 13.8)
CHU Sub-Study: Two 70 mg/mL AI/Pens vs CHU Sub-Study: One 140 mg/mL AI/Pen: Treatment Difference: 0.0 (95% CI -13.8 to 13.3)
CHU Sub-Study: Two 70 mg/mL AI/Pens vs CHU Sub-Study: One 140 mg/mL AI/Pen: Treatment Difference: 0.0 (95% CI -13.8 to 13.3)

Population analysed: CHU Sub-Study Analysis Set: all participants randomized into the CHU substudy who received at least one dose of CHU investigational product (IP).

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-cause mortality: from randomization through the end of study (up to 116 weeks). Treatment-emergent serious and non-serious events: - DBTP: from first dose of IP up to week 24 (end of DBTP) - OLTP: from first dose of OL IP (week 24) up to week 100 (end of OLTP) plus 12 weeks - CHU sub-study: from first dose of sub-study IP up to day 85 (end of sub-study). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
DBTP: Placebo	4 of 136 (2.9%)	55 of 136 (40.4%)	0 of 136
DBTP: Erenumab 28 mg QM	1 of 66 (1.5%)	28 of 66 (42.4%)	0 of 67
DPTP: Erenumab 70 mg QM	1 of 135 (0.7%)	67 of 135 (49.6%)	0 of 135
DBTP: Erenumab 140 mg QM	1 of 137 (0.7%)	58 of 137 (42.3%)	0 of 137
OLTP: Erenumab 70 mg QM	18 of 386 (4.7%)	231 of 386 (59.8%)	0 of 386
OLTP: Erenumab 140 mg QM	9 of 189 (4.8%)	133 of 189 (70.4%)	0 of 189
OLTP Total: Erenumab 70/140 mg QM	27 of 459 (5.9%)	343 of 459 (74.7%)	0 of 459
CHU Sub-Study: Two Erenumab 70 mg/mL AI/Pens	1 of 24 (4.2%)	7 of 24 (29.2%)	0 of 24
CHU Sub-Study: One Erenumab 140 mg/mL AI/Pen	0 of 25 (0%)	7 of 25 (28%)	0 of 25
CHU Sub-Study Total	1 of 49 (2%)	14 of 49 (28.6%)	0 of 49

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 31612482Sakai F, Takeshima T, Tatsuoka Y, Hirata K, Lenz R, Wang Y, Cheng S, Hirama T, Mikol DD. A Randomized Phase 2 Study of Erenumab for the Prevention of Episodic Migraine in Japanese Adults. Headache. 2019 Nov;59(10):1731-1742. doi: 10.1111/head.13652. Epub 2019 Oct 14.
Background: PubMed 35272533Zhou Y, Zhang F, Starcevic Manning M, Hu Z, Hsu CP, Chen PW, Peng C, Loop B, Mytych DT, Paiva da Silva Lima G. Immunogenicity of erenumab: A pooled analysis of six placebo-controlled trials with long-term extensions. Cephalalgia. 2022 Jul;42(8):749-760. doi: 10.1177/03331024221075621. Epub 2022 Mar 10.
BackgroundHiramatsu K, Onizuka Y, Hasebe M, Yoshida R, Numachi Y. Novel Drug for Migraine Prophylaxis: Mode of Action, Efficacy and Safety of Erenumab. Shinryo to Shinyaku (Med Cons New-Remed) 2021:58(11):797-832
Background: PubMed 33764538Sakai F, Takeshima T, Tatsuoka Y, Hirata K, Cheng S, Numachi Y, Peng C, Xue F, Mikol DD. Long-term efficacy and safety during open-label erenumab treatment in Japanese patients with episodic migraine. Headache. 2021 Apr;61(4):653-661. doi: 10.1111/head.14096. Epub 2021 Mar 25.
AmgenTrials clinical trials websiteLink provided by the sponsor.
Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

44 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Erenumab in people with Migraine, run by Amgen at 44 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 44 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 DBTP.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02630459, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2022.