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

NCT ID: NCT01952574

Last Updated: 2022-10-12

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

483 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-08-06

Study Completion Date

2019-11-12

Brief Summary

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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.

Detailed Description

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The study is composed of an initial screening phase (up to 3 weeks), a 4-week baseline phase, a 12-week double-blind treatment phase (DBTP), an open-label treatment phase (OLTP) for up to 256 weeks, and an 8-week safety follow-up (12 weeks after the last dose of investigational product \[IP\]).

In the DBTP participants were to be randomized in a 3:2:2:2 ratio to placebo, erenumab 7 mg, erenumab 21 mg, or erenumab 70 mg.

During the open-label treatment phase, participants were to receive erenumab 70 mg QM from week 12 to week 264. After implementation of Protocol Amendment 3 (07 April 2016), participants remaining in the OLTP increased their dose to erenumab 140 mg QM up to week 264. The safety follow-up increased from an 8-week safety follow-up to a 12-week safety follow-up (16 weeks after the last dose of investigational product).

During the OLTP participants enrolled at sites in the United States could enroll in an optional clinical home use (CHU) substudy, per a country-specific protocol amendment dated 20 June 2016. Participants in the CHU substudy were to be randomized 1:1 into 1 of 2 treatment groups: erenumab 140 mg using a prefilled syringe or erenumab 140 mg using an autoinjector/pen. Day 1 of the CHU substudy corresponded with any OLTP study visit up through Week 256, as long as the participant had received at least 2 doses of erenumab 140 mg. During the CHU substudy, participants initially self-administered IP under site supervision on substudy day 1, and then self-administered IP at home on substudy days 29 and 57.

Conditions

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Migraine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Placebo

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.

Group Type PLACEBO_COMPARATOR

Erenumab

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

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

Erenumab 7 mg QM

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.

Group Type EXPERIMENTAL

Erenumab

Intervention Type DRUG

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

Erenumab 21 mg QM

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.

Group Type EXPERIMENTAL

Erenumab

Intervention Type DRUG

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

Erenumab 70 mg QM

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.

Group Type EXPERIMENTAL

Erenumab

Intervention Type DRUG

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

CHU Substudy: Erenumab 140 mg PFS

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).

Group Type EXPERIMENTAL

Erenumab PFS

Intervention Type DRUG

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

CHU Substudy: Erenumab 140 mg AI/Pen

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).

Group Type EXPERIMENTAL

Erenumab AI/Pen

Intervention Type DRUG

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

Interventions

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Erenumab

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Erenumab PFS

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

Intervention Type DRUG

Erenumab AI/Pen

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

Intervention Type DRUG

Other Intervention Names

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AMG 334 Aimovig™

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Research Site

Phoenix, Arizona, United States

Site Status

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Long Beach, California, United States

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National City, California, United States

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Newport Beach, California, United States

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San Francisco, California, United States

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Santa Monica, California, United States

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Sherman Oaks, California, United States

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Spring Valley, California, United States

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Danbury, Connecticut, United States

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Fairfield, Connecticut, United States

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Stamford, Connecticut, United States

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Bradenton, Florida, United States

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Melbourne, Florida, United States

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Palm Beach Gardens, Florida, United States

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West Palm Beach, Florida, United States

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Decatur, Georgia, United States

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Wichita, Kansas, United States

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Lexington, Kentucky, United States

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Louisville, Kentucky, United States

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Watertown, Massachusetts, United States

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Worcester, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Kalamazoo, Michigan, United States

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Southfield, Michigan, United States

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Plymouth, Minnesota, United States

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Springfield, Missouri, United States

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St Louis, Missouri, United States

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Rochester, New York, United States

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Greensboro, North Carolina, United States

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Raleigh, North Carolina, United States

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Philadelphia, Pennsylvania, United States

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Nashville, Tennessee, United States

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Arlington, Texas, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Salt Lake City, Utah, United States

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Salt Lake City, Utah, United States

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Falls Church, Virginia, United States

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Virginia Beach, Virginia, United States

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Aarhus C, , Denmark

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Glostrup Municipality, , Denmark

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Helsinki, , Finland

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Mikkeli, , Finland

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Oulu, , Finland

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Tampere, , Finland

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Turku, , Finland

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Berlin, , Germany

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Berlin, , Germany

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Berlin, , Germany

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Bochum, , Germany

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Essen, , Germany

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Hamburg, , Germany

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Leipzig, , Germany

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Ålesund, , Norway

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Hamar, , Norway

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Sandvika, , Norway

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Stavanger, , Norway

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Falköping, , Sweden

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Lund, , Sweden

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Stockholm, , Sweden

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Stockholm, , Sweden

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Vällingby, , Sweden

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Countries

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United States Canada Denmark Finland Germany Norway Sweden

References

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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.

Reference Type BACKGROUND
PMID: 26879279 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28835404 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31146544 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 33400330 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35272533 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31707815 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31852816 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33764538 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34928306 (View on PubMed)

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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2012-005331-90

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20120178

Identifier Type: -

Identifier Source: org_study_id

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