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The purpose of this study was to assess the efficacy and safety of erenumab for prevention of migraine in Japanese adults with episodic migraine (EM) and chronic migraine (CM).
Migraine prevention is an area of a large unmet medical need, with existing therapies often having modest efficacy and poor tolerability. Calcitonin gene-related peptide (CGRP) receptor antagonism is a novel approach to migraine preventive therapy. Erenumab is a human monoclonal antibody against canonical CGRP receptor. The present study is a phase 3 trial intended to assess the efficacy and safety of erenumab for prevention of migraine in Japanese adults with episodic migraine (EM) and chronic migraine (CM).
The study consists of a screening period (up to 7 weeks, including a 4-week baseline period), a 24-week double-blind treatment period (DBTP), a 28-week open-label treatment period (OLTP), and an 8-week safety follow-up period (12 weeks after the last dose of investigational product).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Erenumab | Experimental | Participants were to receive erenumab 70 mg once a month for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period. |
|
| Placebo | Placebo Comparator | Participants were to receive placebo to erenumab once a month for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Erenumab | Drug | Administered by subcutaneous injection once a month |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Mean Monthly Migraine Days (MMD) Over Months 4, 5, and 6 of the Double-blind Treatment Period | 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, lasting for ≥ 4 hours, and meeting at least 1 of the following criteria:
The change from baseline in monthly migraine days was calculated as the average number of migraine days per month during the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period minus the number of migraine days during the 4-week baseline period. | 4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days Over Months 4, 5, and 6 of the DBTP | 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, lasting for ≥ 4 hours, and meeting at least 1 of the following criteria:
|
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Inclusion Criteria:
Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures.
Japanese subjects greater than or equal to 20 to less than or equal to 65 years of age upon entry into screening.
History of migraine (with or without aura) for greater than or equal to 12 months before screening according to the International Headache Society Classification ICHD-3 (Headache Classification Committee of the International Headache Society, 2018) based on medical records and/or patient self-report
Migraine frequency: Chronic Migraine (CM) or Episodic Migraine (EM) over the 3 months before screening based on the following criteria:
Exclusion Criteria:
Other exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Matsuyama | Ehime | 790-0925 | Japan | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35272533 | Background | 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. | |
| 35201674 | Background |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either
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.
Eligible participants were randomized 1:1 to erenumab 70 mg or placebo. Randomization was stratified by migraine type (episodic migraine [EM] / chronic migraine [CM]) and migraine preventive treatment status (ever used [prior and/or current] or never used).
This study was conducted at 41 centers in Japan. The study consisted of a 24-week double-blind treatment period (DBTP), a 28-week open-label treatment period (OLTP), followed by an 8-week safety follow-up (12 weeks after the last dose of investigational product).
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo QM | Participants randomized to receive placebo once a month (QM) for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period. |
| FG001 | Erenumab 70 mg QM |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Double-blind Treatment Period |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 2, 2019 | Jan 29, 2021 |
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| Placebo | Drug | Administered by subcutaneous injection once a month |
|
| 4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period |
| Change From Baseline in Mean Monthly Acute Migraine-specific Medication Treatment Days Over Months 4, 5, and 6 of the DBTP | An acute migraine-specific medication treatment day is any calendar day during which a participant took a migraine-specific medication (e.g., triptan or ergotamine). The change from baseline in monthly acute migraine-specific treatment days was calculated as the average number of migraine-specific treatment days per month during the last 3 months of the 24-week double-blind treatment period minus the number of migraine-specific treatment days during the 4-week baseline period. | 4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period |
| Kasuga-shi |
| Fukuoka |
| 816-0802 |
| Japan |
| Research Site | Kasuga-shi | Fukuoka | 816-0824 | Japan |
| Research Site | Hiroshima | Hiroshima | 730-0031 | Japan |
| Research Site | Hiroshima | Hiroshima | 730-0845 | Japan |
| Research Site | Sapporo | Hokkaido | 003-0003 | Japan |
| Research Site | Sapporo | Hokkaido | 007-0836 | Japan |
| Research Site | Sapporo | Hokkaido | 060-8570 | Japan |
| Research Site | Kobe | Hyōgo | 658-0064 | Japan |
| Research Site | Kahoku-gun | Ishikawa-ken | 929-0342 | Japan |
| Research Site | Morioka | Iwate | 020-8505 | Japan |
| Research Site | Takamatsu | Kagawa-ken | 769-0103 | Japan |
| Research Site | Kagoshima | Kagoshima-ken | 892-0844 | Japan |
| Research Site | Kawasaki-shi | Kanagawa | 211-8588 | Japan |
| Research Site | Kawasaki-shi | Kanagawa | 216-8511 | Japan |
| Research Site | Kochi | Kochi | 780-8011 | Japan |
| Research Site | Kumamoto | Kumamoto | 861-2101 | Japan |
| Research Site | Kumamoto | Kumamoto | 862-8505 | Japan |
| Research Site | Kyoto | Kyoto | 600-8811 | Japan |
| Research Site | Sendai | Miyagi | 982-0014 | Japan |
| Research Site | Ōita | Oita Prefecture | 870-0831 | Japan |
| Research Site | Osaka | Osaka | 556-0017 | Japan |
| Research Site | Toyonaka-shi | Osaka | 560-0012 | Japan |
| Research Site | Saga | Saga-ken | 840-0806 | Japan |
| Research Site | Iruma-gun | Saitama | 350-0495 | Japan |
| Research Site | Saitama-shi | Saitama | 338-8577 | Japan |
| Research Site | Tokorozawa-shi | Saitama | 359-1141 | Japan |
| Research Site | Shizuoka | Shizuoka | 420-0853 | Japan |
| Research Site | Shimotsuga-gun | Tochigi | 321-0293 | Japan |
| Research Site | Chofu-shi | Tokyo | 182-0006 | Japan |
| Research Site | Hachioji-shi | Tokyo | 192-0032 | Japan |
| Research Site | Minato-ku | Tokyo | 108-0075 | Japan |
| Research Site | Minato-ku | Tokyo | 108-8642 | Japan |
| Research Site | Shibuya-ku | Tokyo | 151-0051 | Japan |
| Research Site | Shinjuku-ku | Tokyo | 160-0017 | Japan |
| Research Site | Tottori-shi | Tottori | 680-0045 | Japan |
| Research Site | Yonago-shi | Tottori | 683-0033 | Japan |
| Research Site | Toyama | Toyama | 930-0803 | Japan |
| Research Site | Hofu-shi | Yamaguchi | 747-0802 | Japan |
| Research Site | Yamaguchi | Yamaguchi | 754-0002 | Japan |
| Research Site | Kai-shi | Yamanashi | 400-0124 | Japan |
| Hirata K, Takeshima T, Sakai F, Imai N, Matsumori Y, Tatsuoka Y, Numachi Y, Yoshida R, Peng C, Mikol DD, Lima GPDS, Cheng S. Early onset of efficacy with erenumab for migraine prevention in Japanese patients: Analysis of two randomized, double-blind, placebo-controlled studies. Brain Behav. 2022 Mar;12(3):e2526. doi: 10.1002/brb3.2526. Epub 2022 Feb 24. |
| Background | 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 |
| 34537006 | Background | Hirata K, Sakai F, Takeshima T, Imai N, Matsumori Y, Yoshida R, Numachi Y, Peng C, Mikol DD, Cheng S. Efficacy and safety of erenumab in Japanese migraine patients with prior preventive treatment failure or concomitant preventive treatment: subgroup analyses of a phase 3, randomized trial. J Headache Pain. 2021 Sep 18;22(1):110. doi: 10.1186/s10194-021-01313-8. |
| 34153117 | Background | Takeshima T, Sakai F, Hirata K, Imai N, Matsumori Y, Yoshida R, Peng C, Cheng S, Mikol DD. Erenumab treatment for migraine prevention in Japanese patients: Efficacy and safety results from a Phase 3, randomized, double-blind, placebo-controlled study. Headache. 2021 Jun;61(6):927-935. doi: 10.1111/head.14138. Epub 2021 Jun 21. |
| 37597868 | Background | Hirata K, Takeshima T, Sakai F, Numachi Y, Yoshida R, Koukakis R, Hasebe M, Yui D, da Silva Lima GP, Cheng S. Long-term efficacy and safety of erenumab in Japanese patients with episodic and chronic migraine: results from a 28-week open-label treatment period of a randomised trial. BMJ Open. 2023 Aug 18;13(8):e068616. doi: 10.1136/bmjopen-2022-068616. |
| 37698837 | Background | Kitamura S, Takeshima T, Yui D, da Silva Lima GP, Koukakis R, Peng C, Yoshida R, Numachi Y, Hasebe M. Efficacy of Erenumab for Migraine Prevention in Japanese Patients with Episodic and Chronic Migraine: Results of a Post-Hoc Pooled Analysis. Neurol Ther. 2023 Dec;12(6):1993-2006. doi: 10.1007/s40120-023-00538-w. Epub 2023 Sep 12. |
| 41991782 | Derived | Dias-Barbosa C, Igarashi H, Duenas A, Hareendran A, Kitamura S, Tanaka S, Sanno N, Doi H, Nagamitsu T, Tatsuoka Y, Matsumori Y, Hasebe M, Takeshima T. Experiences of Migraine and Erenumab Treatment in Japan: Qualitative Interviews with Clinical Trial Participants. Patient. 2026 Apr 16. doi: 10.1007/s40271-026-00813-6. Online ahead of print. |
Participants randomized to receive erenumab 70 mg once a month for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period. |
| COMPLETED |
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| NOT COMPLETED |
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| Open-label Treatment Period |
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The full analysis set (FAS) included all participants who were randomized in the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo QM | Participants randomized to receive placebo once a month (QM) for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period. |
| BG001 | Erenumab 70 mg QM | Participants randomized to receive erenumab 70 mg once a month for 24 weeks during the double-blind treatment period followed by erenumab 70 mg once a month for 28 weeks during the open-label treatment period. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Migraine Type | Episodic migraine is characterized by migraine with fewer than 15 headache days per month. Chronic migraine is characterized by 15 or more headache days per month (where at least 8 of those days are migraine days). | Count of Participants | Participants |
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| Prior Migraine Preventive Treatment Status | Count of Participants | Participants |
| ||||||||||||||||
| Monthly Migraine Days | 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, lasting for ≥ 4 hours and meeting protocol-specified criteria. Monthly migraine days were calculated as the number of migraine days in the 4-week baseline period. | Mean | Standard Deviation | days / month |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Mean Monthly Migraine Days (MMD) Over Months 4, 5, and 6 of the Double-blind Treatment Period | 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, lasting for ≥ 4 hours, and meeting at least 1 of the following criteria:
The change from baseline in monthly migraine days was calculated as the average number of migraine days per month during the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period minus the number of migraine days during the 4-week baseline period. | The efficacy analysis set included randomized participants who received at least 1 dose of investigational product and had at least 1 change from baseline measurement in MMD during the DBTP. Observed data. | Posted | Least Squares Mean | 95% Confidence Interval | migraine days / month | 4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period |
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| Secondary | Percentage of Participants With at Least a 50% Reduction From Baseline in Mean Monthly Migraine Days Over Months 4, 5, and 6 of the DBTP | 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, lasting for ≥ 4 hours, and meeting at least 1 of the following criteria:
| Efficacy analysis set; participants with missing data were counted as non-responders. | Posted | Number | percentage of participants | 4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period |
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| Secondary | Change From Baseline in Mean Monthly Acute Migraine-specific Medication Treatment Days Over Months 4, 5, and 6 of the DBTP | An acute migraine-specific medication treatment day is any calendar day during which a participant took a migraine-specific medication (e.g., triptan or ergotamine). The change from baseline in monthly acute migraine-specific treatment days was calculated as the average number of migraine-specific treatment days per month during the last 3 months of the 24-week double-blind treatment period minus the number of migraine-specific treatment days during the 4-week baseline period. | Efficacy analysis set; observed data | Posted | Least Squares Mean | 95% Confidence Interval | days / month | 4-week baseline period and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment period |
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DBTP: From first dose of study drug up to the first dose of open-label study drug (24 weeks) for participants who entered the OLTP, or up to 12 weeks after the last dose (up to 32 weeks) for participants who did not enter the OLTP. OLTP: From first dose of study drug in the OLTP up to 12 weeks after last dose (up to 36 weeks).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Double-blind Treatment Period: Placebo QM | Participants received placebo once a month for 24 weeks during the double-blind treatment period. | 0 | 131 | 2 | 131 | 40 | 131 |
| EG001 | Double-blind Treatment Period: Erenumab 70 mg QM | Participants received erenumab 70 mg once a month for 24 weeks during the double-blind treatment period. | 0 | 130 | 2 | 130 | 44 | 130 |
| EG002 | Open-label Treatment Period: Erenumab 70 mg QM | Participants received erenumab 70 mg once a month for 28 weeks during the open-label treatment period. | 0 | 254 | 7 | 254 | 62 | 254 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Appendicitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Brain contusion | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Clavicle fracture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Skull fracture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Wound | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Ovarian adenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
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| Subarachnoid haemorrhage | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Foot fracture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Meniscus injury | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Tendon rupture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Spinal osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Laryngeal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 | medinfo@amgen.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 15, 2020 | Jan 29, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D008881 | Migraine Disorders |
| ID | Term |
|---|---|
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C000605816 | erenumab |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Chronic migraine |
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| Never used |
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