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

NCT01952574 | Completed Phase 2 Results

• 2 other identifiers: 201201782012-005331-90
• Study Type: interventional
• Target: 483
• Locations: 7 countries
• Sites: 66

Brief Summary

A study to evaluate the effect of erenumab compared to placebo on the change from baseline in monthly migraine days in participants with episodic migraine.

Conditions

Migraine

Keywords

migraine, headache, prevention, prophylaxis

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Monthly Migraine Days at Week 12

  A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined as a migraine with or without aura. The change from baseline in monthly migraine days was calculated as the number of migraine days during the last 4 weeks of the 12-week double-blind treatment phase - the number of migraine days during the 4-week baseline phase.

  4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase

• CHU Substudy: Number of Participants Who Self-administered a Full Dose, Partial Dose, or No Dose of Erenumab

  To assess participants ability to administer a full dose of erenumab in home-use at day 29 (week 4) and day 57 (week 8), site staff called participants and asked whether the participant administered a full, partial, or no dose of erenumab. A full dose means that the entire volume of both prefilled syringes or autoinjector/pens were injected. Discontinued prior to dosing day indicates participants who had discontinued the investigational product and did not attempt to self-administer on day 29 or 57.

  CHU substudy day 29 (week 4) and day 57 (week 8)

Secondary Outcomes (7)

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

  4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase

• Change From Baseline in Monthly Migraine Attacks at Week 12

  4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase

• Number of Participants With Treatment-emergent Adverse Events in the Double-blind Treatment Phase

  From first dose of study drug in the double-blind treatment phase until the first dose of study drug in the open-label treatment phase (12 weeks) or up to 12 weeks after last dose for participants who did not enter the open-label treatment phase.

• Number of Participants With Treatment-emergent Adverse Events in the Open-label Treatment Phase

  From first dose in the open-label treatment phase up to 12 weeks (participants receiving 70 mg only) or 16 weeks (participants with dose increased to 140 mg) after the last dose; a maximum of 268 weeks.

• CHU Substudy: Number of Participants With Treatment-emergent Adverse Events During the CHU Substudy

  From first dose in the CHU substudy to end of substudy (up to 12 weeks)

Study Arms (6)

Placebo

PLACEBO COMPARATOR

Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.

Drug: Erenumab; Drug: Placebo

Erenumab 7 mg QM

EXPERIMENTAL

Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.

Drug: Erenumab

Erenumab 21 mg QM

EXPERIMENTAL

Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.

Drug: Erenumab

Erenumab 70 mg QM

EXPERIMENTAL

Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.

Drug: Erenumab

CHU Substudy: Erenumab 140 mg PFS

EXPERIMENTAL

Participants in the open-label treatment phase in the United States randomized to self-administer 140 mg erenumab via two 70 mg injections using a prefilled syringe (PFS) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).

Drug: Erenumab PFS

CHU Substudy: Erenumab 140 mg AI/Pen

EXPERIMENTAL

Participants in the open-label treatment phase in the United States randomized to self-administer 140 mg erenumab via two 70 mg injections using an autoinjector/pen (AI)/pen) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).

Drug: Erenumab AI/Pen

Interventions

Erenumab DRUG

Administered by study site staff once a month (QM) as a subcutaneous injection

Also known as: AMG 334, Aimovig™

Erenumab 21 mg QM; Erenumab 7 mg QM; Erenumab 70 mg QM; Placebo

Placebo DRUG

Administered by study site staff once a month (QM) as a subcutaneous injection

Placebo

Erenumab PFS DRUG

Erenumab supplied in a single-use prefilled syringe for self-administration in the CHU substudy

CHU Substudy: Erenumab 140 mg PFS

Erenumab AI/Pen DRUG

Erenumab supplied in a single-use autoinjector/pen for self-administration in the CHU substudy

CHU Substudy: Erenumab 140 mg AI/Pen

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• History of migraine for more than12 months prior to screening
• Migraine frequency: ≥ 4 and ≤ 14 migraine days per month in each of the 3 months prior to screening and during baseline phase
• Headache frequency: \< 15 headache days per month (with \> 50% of the headache days being migraine days) in each of the 3 months prior to screening and during baseline phase
• Demonstrated at least 80% compliance with the eDiary during baseline phase

You may not qualify if:

• Older than 50 years of age at migraine onset
• History of cluster headache or basilar or hemiplegic migraine headache
• Unable to differentiate migraine from other headaches
• No therapeutic response with \> 2 of the following eight medication categories for prophylactic treatment of migraine after an adequate therapeutic trial. Medication categories are:
• 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: Venlafaxine, desvenlafaxine, duloxetine, milnacipran
• Category 6: Flunarizine, verapamil
• Category 7: Lisinopril, candesartan
• Category 8: Butterbur, feverfew, magnesium (≥ 600 mg/day), riboflavin (≥ 100 mg/day)
• Overuse of acute migraine medications in any month during the 3 months prior to screening or during screening

Sponsors & Collaborators

• Amgen: lead

Study Sites (66)

Research Site

Phoenix, Arizona, 85032, United States

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Long Beach, California, 90806, United States

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National City, California, 91950, United States

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Newport Beach, California, 92663, United States

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San Francisco, California, 94109, United States

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Santa Monica, California, 90404, United States

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Sherman Oaks, California, 91403, United States

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Spring Valley, California, 91978, United States

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Danbury, Connecticut, 06810, United States

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Fairfield, Connecticut, 06824, United States

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Stamford, Connecticut, 06905, United States

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Bradenton, Florida, 34205, United States

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Melbourne, Florida, 32935, United States

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Palm Beach Gardens, Florida, 33410, United States

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West Palm Beach, Florida, 33407, United States

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Decatur, Georgia, 30033, United States

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Wichita, Kansas, 67207, United States

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Lexington, Kentucky, 40513, United States

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Louisville, Kentucky, 40213, United States

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Watertown, Massachusetts, 02472, United States

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Worcester, Massachusetts, 01605, United States

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Ann Arbor, Michigan, 48104, United States

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Kalamazoo, Michigan, 49009, United States

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Southfield, Michigan, 48034, United States

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Plymouth, Minnesota, 55441, United States

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Springfield, Missouri, 65807, United States

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St Louis, Missouri, 63141, United States

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Rochester, New York, 14609, United States

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Greensboro, North Carolina, 27405, United States

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Raleigh, North Carolina, 27612, United States

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Philadelphia, Pennsylvania, 19107, United States

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Nashville, Tennessee, 37203, United States

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Arlington, Texas, 76017, United States

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Austin, Texas, 78731, United States

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Dallas, Texas, 75214, United States

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Dallas, Texas, 75231, United States

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Houston, Texas, 77074, United States

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Salt Lake City, Utah, 84106, United States

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Salt Lake City, Utah, 84124, United States

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Falls Church, Virginia, 22042, United States

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Virginia Beach, Virginia, 23454, United States

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Toronto, Ontario, M4S 1Y2, Canada

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Montreal, Quebec, H2L 4M1, Canada

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Aarhus C, 8000, Denmark

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Glostrup Municipality, 2600, Denmark

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Helsinki, 00100, Finland

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Mikkeli, 50100, Finland

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Oulu, 90220, Finland

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Tampere, 33100, Finland

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Turku, 20100, Finland

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Berlin, 10117, Germany

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Berlin, 10409, Germany

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Berlin, 10435, Germany

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Bochum, 44789, Germany

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Essen, 45133, Germany

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Hamburg, 20246, Germany

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Leipzig, 04107, Germany

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Ålesund, 6003, Norway

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Hamar, 2317, Norway

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Sandvika, 1337, Norway

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Stavanger, 4005, Norway

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Falköping, 521 37, Sweden

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Lund, 222 22, Sweden

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Stockholm, 112 45, Sweden

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Stockholm, 114 33, Sweden

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Vällingby, 162 68, Sweden

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Related Publications (10)

• Sun H, Dodick DW, Silberstein S, Goadsby PJ, Reuter U, Ashina M, Saper J, Cady R, Chon Y, Dietrich J, Lenz R. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Apr;15(4):382-90. doi: 10.1016/S1474-4422(16)00019-3. Epub 2016 Feb 12.

  PMID: 26879279 BACKGROUND

• Ashina M, Dodick D, Goadsby PJ, Reuter U, Silberstein S, Zhang F, Gage JR, Cheng S, Mikol DD, Lenz RA. Erenumab (AMG 334) in episodic migraine: Interim analysis of an ongoing open-label study. Neurology. 2017 Sep 19;89(12):1237-1243. doi: 10.1212/WNL.0000000000004391. Epub 2017 Aug 23.

  PMID: 28835404 BACKGROUND

• Ashina M, Goadsby PJ, Reuter U, Silberstein S, Dodick D, Rippon GA, Klatt J, Xue F, Chia V, Zhang F, Cheng S, Mikol DD. Long-term safety and tolerability of erenumab: Three-plus year results from a five-year open-label extension study in episodic migraine. Cephalalgia. 2019 Oct;39(11):1455-1464. doi: 10.1177/0333102419854082. Epub 2019 May 30.

  PMID: 31146544 BACKGROUND

• Cheng S, Picard H, Zhang F, Eisele O, Mikol DD. Efficacy and safety of erenumab for migraine prevention: an overview. Japanese Journal of Headache. 2019; 45 : 493-505.

  BACKGROUND

• Ashina M, Goadsby PJ, Reuter U, Silberstein S, Dodick DW, Xue F, Zhang F, Paiva da Silva Lima G, Cheng S, Mikol DD. Long-term efficacy and safety of erenumab in migraine prevention: Results from a 5-year, open-label treatment phase of a randomized clinical trial. Eur J Neurol. 2021 May;28(5):1716-1725. doi: 10.1111/ene.14715. Epub 2021 Jan 20.

  PMID: 33400330 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

• Ashina M, Kudrow D, Reuter U, Dolezil D, Silberstein S, Tepper SJ, Xue F, Picard H, Zhang F, Wang A, Zhou Y, Hong F, Klatt J, Mikol DD. Long-term tolerability and nonvascular safety of erenumab, a novel calcitonin gene-related peptide receptor antagonist for prevention of migraine: A pooled analysis of four placebo-controlled trials with long-term extensions. Cephalalgia. 2019 Dec;39(14):1798-1808. doi: 10.1177/0333102419888222. Epub 2019 Nov 10.

  PMID: 31707815 BACKGROUND

• Kudrow D, Pascual J, Winner PK, Dodick DW, Tepper SJ, Reuter U, Hong F, Klatt J, Zhang F, Cheng S, Picard H, Eisele O, Wang J, Latham JN, Mikol DD. Vascular safety of erenumab for migraine prevention. Neurology. 2020 Feb 4;94(5):e497-e510. doi: 10.1212/WNL.0000000000008743. Epub 2019 Dec 18.

  PMID: 31852816 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

• Ashina M, Goadsby PJ, Dodick DW, Tepper SJ, Xue F, Zhang F, Brennan F, Paiva da Silva Lima G. Assessment of Erenumab Safety and Efficacy in Patients With Migraine With and Without Aura: A Secondary Analysis of Randomized Clinical Trials. JAMA Neurol. 2022 Feb 1;79(2):159-168. doi: 10.1001/jamaneurol.2021.4678.

  PMID: 34928306 DERIVED

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, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In the DBTP participants were randomized to one of four arms. In the optional CHU substudy participants were randomized into one of two treatment groups.

Study Record Dates

• First Submitted: August 30, 2013
• First Posted: September 30, 2013
• Study Start: August 6, 2013
• Primary Completion: September 25, 2014
• Study Completion: November 12, 2019
• Last Updated: October 12, 2022
• Results First Posted: July 10, 2018

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 URL below.

Locations

NO (4); DE (7); CA (2); US (41); SE (5); DK (2); FI (5)