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

NCT02630459 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 20120309
• Study Type: interventional
• Target: 475
• Locations: 1 country
• Sites: 44

Brief 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.

Conditions

Migraine

Keywords

Migraine Prevention; Headache; Prophylaxis

Outcome Measures

Primary Outcomes (2)

• 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.

  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.)

  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

  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

  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

  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

  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

  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.

Study Arms (7)

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.

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.

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.

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.

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.

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

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

Drug: Erenumab

Interventions

Placebo DRUG

placebo via subcutaneous injection

Double Blind Treatment Phase (DBTP): Placebo

Erenumab DRUG

erenumab via subcutaneous injection

Also known as: AMG 334, Aimovig™

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

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• \- Subjects must have provided informed consent for the substudy. Subjects enrolling in the CHU substudy must have received open-label 140 mg erenumab for at least 1 dose.

You may not qualify if:

• 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,
• 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,

Sponsors & Collaborators

• Amgen: lead

Study Sites (44)

Research Site

Kamogawa-shi, Chiba, 296-0041, Japan

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Saijo-shi, Ehime, 793-0030, Japan

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Ota-shi, Gunma, 373-8585, Japan

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Hiroshima, Hiroshima, 730-8518, Japan

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Sapporo, Hokkaido, 060-0004, Japan

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Sapporo, Hokkaido, 060-8570, Japan

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Sapporo, Hokkaido, 063-0005, Japan

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Kobe, Hyōgo, 658-0064, Japan

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Tsukuba, Ibaraki, 305-8576, Japan

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Kahoku-gun, Ishikawa-ken, 929-0342, Japan

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Morioka, Iwate, 020-8505, Japan

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Kagoshima, Kagoshima-ken, 892-0844, Japan

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Kawasaki-shi, Kanagawa, 211-8533, Japan

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Kawasaki-shi, Kanagawa, 211-8588, Japan

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Kawasaki-shi, Kanagawa, 216-8511, Japan

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Kumamoto, Kumamoto, 861-2101, Japan

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Kumamoto, Kumamoto, 862-8505, Japan

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Kyoto, Kyoto, 600-8811, Japan

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Sendai, Miyagi, 982-0014, Japan

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Osaka, Osaka, 556-0017, Japan

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Osakasayama-shi, Osaka, 589-8511, Japan

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Toyonaka-shi, Osaka, 560-0012, Japan

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Saga, Saga-ken, 840-0806, Japan

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Iruma-gun, Saitama, 350-0495, Japan

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Saitama-shi, Saitama, 338-8577, Japan

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Tokorozawa-shi, Saitama, 359-1141, Japan

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Shizuoka, Shizuoka, 420-0853, Japan

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Shimotsuga-gun, Tochigi, 321-0293, Japan

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Bunkyo-ku, Tokyo, 113-8431, Japan

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Bunkyo-ku, Tokyo, 113-8603, Japan

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Chofu-shi, Tokyo, 182-0006, Japan

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Chuo-ku, Tokyo, 104-8560, Japan

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Hachioji-shi, Tokyo, 192-0032, Japan

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Minato-ku, Tokyo, 106-6106, Japan

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Minato-ku, Tokyo, 108-8642, Japan

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Shibuya-ku, Tokyo, 151-0051, Japan

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Shinjuku-ku, Tokyo, 160-0017, Japan

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Shinjuku-ku, Tokyo, 160-8582, Japan

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Yonago, Tottori, 683-8504, Japan

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Toyama, Toyama, 930-0194, Japan

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Toyama, Toyama, 930-0803, Japan

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Hofu-shi, Yamaguchi, 747-0802, Japan

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Yamaguchi, Yamaguchi, 754-0002, Japan

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Kai-shi, Yamanashi, 400-0124, Japan

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Related Publications (4)

• 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.

  PMID: 31612482 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.

  PMID: 35272533 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

  BACKGROUND

• 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.

  PMID: 33764538 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Migraine Disorders; Headache

Interventions

erenumab

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2015
• First Posted: December 15, 2015
• Study Start: January 6, 2016
• Primary Completion: September 25, 2017
• Study Completion: June 5, 2019
• Last Updated: October 12, 2022
• Results First Posted: March 13, 2019

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

JP (44)