Clinical trial NCT01952574: Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Migraine Prevention
Official title: A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Migraine Prevention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Migraine
Keywords: migraine, headache, prevention, prophylaxis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-09-30
Enrollment: 483
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: PREVENTION

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Monthly Migraine Days at Week 12
timeFrame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
measure: CHU Substudy: Number of Participants Who Self-administered a Full Dose, Partial Dose, or No Dose of Erenumab
timeFrame: CHU substudy day 29 (week 4) and day 57 (week 8)
Secondary outcomes:
measure: Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Week 12
timeFrame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
measure: Change From Baseline in Monthly Migraine Attacks at Week 12
timeFrame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
measure: Number of Participants With Treatment-emergent Adverse Events in the Double-blind Treatment Phase
timeFrame: 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.
measure: Number of Participants With Treatment-emergent Adverse Events in the Open-label Treatment Phase
timeFrame: 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.
measure: CHU Substudy: Number of Participants With Treatment-emergent Adverse Events During the CHU Substudy
timeFrame: From first dose in the CHU substudy to end of substudy (up to 12 weeks)
measure: Number of Participants Who Developed Anti-erenumab Antibodies During the Double-blind Treatment Phase
timeFrame: 12 weeks
measure: Number of Participants Who Developed Anti-erenumab Antibodies During the Open-label Treatment Phase
timeFrame: From week 12 up to 12 weeks (participants receiving 70 mg only) or 16 weeks (participants with dose increased to 140 mg) after the last dose; maximum 268 weeks.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Long Beach
country: United States
facility: Research Site
state: California
city: National City
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Santa Monica
country: United States
facility: Research Site
state: California
city: Sherman Oaks
country: United States
facility: Research Site
state: California
city: Spring Valley
country: United States
facility: Research Site
state: California
city: Danbury
country: United States
facility: Research Site
state: Connecticut
city: Fairfield
country: United States
facility: Research Site
state: Connecticut
city: Stamford
country: United States
facility: Research Site
state: Connecticut
city: Bradenton
country: United States
facility: Research Site
state: Florida
city: Melbourne
country: United States
facility: Research Site
state: Florida
city: Palm Beach Gardens
country: United States
facility: Research Site
state: Florida
city: West Palm Beach
country: United States
facility: Research Site
state: Florida
city: Decatur
country: United States
facility: Research Site
state: Georgia
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Watertown
country: United States
facility: Research Site
state: Massachusetts
city: Worcester
country: United States
facility: Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Kalamazoo
country: United States
facility: Research Site
state: Michigan
city: Southfield
country: United States
facility: Research Site
state: Michigan
city: Plymouth
country: United States
facility: Research Site
state: Minnesota
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Springfield
country: United States
facility: Research Site
state: Missouri
city: Rochester
country: United States
facility: Research Site
state: New York
city: Greensboro
country: United States
facility: Research Site
state: North Carolina
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Arlington
country: United States
facility: Research Site
state: Texas
city: Austin
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Falls Church
country: United States
facility: Research Site
state: Virginia
city: Virginia Beach
country: United States
facility: Research Site
state: Virginia
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Aarhus C
country: Denmark
facility: Research Site
city: Glostrup
country: Denmark
facility: Research Site
city: Helsinki
country: Finland
facility: Research Site
city: Mikkeli
country: Finland
facility: Research Site
city: Oulu
country: Finland
facility: Research Site
city: Tampere
country: Finland
facility: Research Site
city: Turku
country: Finland
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bochum
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Hamar
country: Norway
facility: Research Site
city: Sandvika
country: Norway
facility: Research Site
city: Stavanger
country: Norway
facility: Research Site
city: Ålesund
country: Norway
facility: Research Site
city: Falköping
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Vällingby
country: Sweden
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.