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

Migraine Clinical Trial

— STRIVE  

Official title:

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Migraine Prevention

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02456740
• Other study ID #: 20120296
• Secondary ID: 2014-004464-38
• Status: Completed
• Phase: Phase 3
• Start date: July 17, 2015
• Est. completion date: June 19, 2017

Study information

• Verified date: October 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study was to evaluate the effect of erenumab compared to placebo on the change from baseline in monthly migraine days.

Description:

This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. The trial consisted of four phases: screening (≤ 3 weeks of initial screening and a 4-week baseline phase); the double-blind treatment phase (24 weeks) in which participants received placebo or erenumab 70 mg or 140 mg daily; the active-treatment phase, in which participants underwent repeat randomization and were assigned to receive 70 mg or 140 mg of erenumab (28 weeks); and a safety follow-up phase (12 weeks).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 955
• Est. completion date: June 19, 2017
• Est. primary completion date: September 5, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• History of migraine (with or without aura) for = 12 months prior to screening according to the International Headache Society (IHS) International Classification of Headache Disorders (ICHD-3) classification

• Migraine frequency: = 4 and < 15 migraine days per month on average across the 3 months prior to screening and during baseline

• Headache frequency: < 15 headache days per month on average across the 3 months prior to screening and baseline

• Demonstrated at least 80% compliance with the eDiary.

Exclusion Criteria:

• Older than 50 years of age at migraine onset

• History of cluster headache or hemiplegic migraine headache

• Unable to differentiate migraine from other headache

• No therapeutic response with > 2 medication categories for prophylactic treatment of migraine after an adequate therapeutic trial

• Used a prohibited medication, device, or procedure within 2 months prior to the start of the baseline phase or during the baseline phase

• Concomitant use of 2 or more medications with possible migraine prophylactic effects within 2 months prior to the start of the baseline phase or during the baseline phase. If only 1 prophylactic medication is used, the dose must be stable within 2 months prior to the start of the baseline phase and throughout the study

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

Intervention

Drug:
• Erenumab
Administered by subcutaneous injection once a month
• Placebo
Administered by subcutaneous injection once a month

Locations

Country	Name	City	State
Austria	Research Site	Innsbruck
Austria	Research Site	Linz
Austria	Research Site	Wien
Austria	Research Site	Wien
Belgium	Research Site	Brussel
Belgium	Research Site	Gent
Belgium	Research Site	Hasselt
Belgium	Research Site	Liege
Belgium	Research Site	Lodelinsart
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Levis	Quebec
Canada	Research Site	Markham	Ontario
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Surrey	British Columbia
Czechia	Research Site	Brno
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Olomouc
Czechia	Research Site	Pardubice
Czechia	Research Site	Praha 2
Czechia	Research Site	Praha 4
Finland	Research Site	Helsinki
Finland	Research Site	Kuopio
Finland	Research Site	Oulu
Finland	Research Site	Turku
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin (Hellersdorf)
Germany	Research Site	Bochum
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hüttenberg
Germany	Research Site	Kiel
Germany	Research Site	Köln
Germany	Research Site	Leipzig
Germany	Research Site	Leipzig
Germany	Research Site	München
Germany	Research Site	Wiesbaden
Germany	Research Site	Würzburg
Netherlands	Research Site	Leiden
Poland	Research Site	Krakow
Poland	Research Site	Lodz
Poland	Research Site	Lublin
Poland	Research Site	Poznan
Poland	Research Site	Swidnik
Poland	Research Site	Warszawa
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Komarno
Slovakia	Research Site	Lucenec
Sweden	Research Site	Falköping
Sweden	Research Site	Helsingborg
Sweden	Research Site	Stockholm
Sweden	Research Site	Stockholm
Sweden	Research Site	Uddevalla
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Antalya
Turkey	Research Site	Bursa
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Izmir
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Northwood
United Kingdom	Research Site	Oxford
United Kingdom	Research Site	Sidcup
United Kingdom	Research Site	Stoke on Trent
United States	Research Site	Amherst	New York
United States	Research Site	Anaheim	California
United States	Research Site	Atlanta	Georgia
United States	Research Site	Austin	Texas
United States	Research Site	Bedford	Texas
United States	Research Site	Boise	Idaho
United States	Research Site	Boulder	Colorado
United States	Research Site	Bradenton	Florida
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Cleveland	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Cumberland	Rhode Island
United States	Research Site	Des Moines	Iowa
United States	Research Site	Durham	North Carolina
United States	Research Site	East Hartford	Connecticut
United States	Research Site	Edgewood	Kentucky
United States	Research Site	Encino	California
United States	Research Site	Evansville	Indiana
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Irvine	California
United States	Research Site	Irving	Texas
United States	Research Site	Jacksonville	Florida
United States	Research Site	Kansas City	Missouri
United States	Research Site	Leesburg	Florida
United States	Research Site	Los Alamitos	California
United States	Research Site	Memphis	Tennessee
United States	Research Site	Metairie	Louisiana
United States	Research Site	Miami	Florida
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Bedford	Massachusetts
United States	Research Site	New Orleans	Louisiana
United States	Research Site	Newport Beach	California
United States	Research Site	Newton	Kansas
United States	Research Site	Ocala	Florida
United States	Research Site	Orlando	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Plainview	New York
United States	Research Site	Plymouth	Minnesota
United States	Research Site	Port Royal	South Carolina
United States	Research Site	Portland	Oregon
United States	Research Site	Rancho Mirage	California
United States	Research Site	Redlands	California
United States	Research Site	Rochester	New York
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Salt Lake City	Utah
United States	Research Site	San Antonio	Texas
United States	Research Site	Sherman Oaks	California
United States	Research Site	Simi Valley	California
United States	Research Site	Spring Valley	California
United States	Research Site	Springfield	Missouri
United States	Research Site	Stamford	Connecticut
United States	Research Site	Sunrise	Florida
United States	Research Site	Waterbury	Connecticut
United States	Research Site	West Jordan	Utah
United States	Research Site	West Palm Beach	Florida
United States	Research Site	Wichita	Kansas
United States	Research Site	Willoughby Hills	Ohio
United States	Research Site	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Czechia,  Finland,  Germany,  Netherlands,  Poland,  Slovakia,  Sweden,  Turkey,  United Kingdom, 

References & Publications (10)

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. — View Citation

Buse DC, Lipton RB, Hallström Y, Reuter U, Tepper SJ, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. Migraine-related disability, impact, and health-related quality of life among patients with episodic migraine receiving preventive treatment with erenumab. Cephalalgia. 2018 Sep;38(10):1622-1631. doi: 10.1177/0333102418789072. Epub 2018 Aug 7. — View 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.

Goadsby PJ, Reuter U, Hallström Y, Broessner G, Bonner JH, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. A Controlled Trial of Erenumab for Episodic Migraine. N Engl J Med. 2017 Nov 30;377(22):2123-2132. doi: 10.1056/NEJMoa1705848. — View Citation

Kawata AK, Ladd MK, Lipton RB, Buse DC, Bensink M, Shah S, Hareendran A, Mannix S, Mikol D. Reducing the physical, social, and emotional impact of episodic migraine: Results from erenumab STRIVE and ARISE phase III randomized trials. Headache. 2022 Feb;62(2):159-168. doi: 10.1111/head.14258. Epub 2022 Feb 8. — View 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. Erratum in: Neurology. 2020 Jun 9;94(23):1052. — View Citation

Lipton RB, Dodick DW, Kudrow D, Reuter U, Tenenbaum N, Zhang F, Lima GPDS, Chou DE, Mikol DD. Reduction in migraine pain intensity in patients treated with erenumab: A post hoc analysis of two pivotal randomized studies. Cephalalgia. 2021 Dec;41(14):1458-1466. doi: 10.1177/03331024211028966. Epub 2021 Aug 18. — View Citation

McAllister PJ, Turner I, Reuter U, Wang A, Scanlon J, Klatt J, Chou DE, Paiva da Silva Lima G. Timing and durability of response to erenumab in patients with episodic migraine. Headache. 2021 Nov;61(10):1553-1561. doi: 10.1111/head.14233. Epub 2021 Nov 28. — View Citation

Yucel A, Thach A, Kumar S, Loden C, Bensink M, Goldfarb N. Estimating the economic burden of migraine on US employers. Am J Manag Care. 2020 Dec 1;26(12):e403-e408. doi: 10.37765/ajmc.2020.88547. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Mean Monthly Migraine Days to the Last 3 Months 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.; 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 phase - the number of migraine days during the 4-week baseline phase.	4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase
Secondary	Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days in the Last 3 Months of the Double-blind Treatment Phase	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 without aura or a migraine with aura.; At least a 50% reduction from baseline in monthly migraine days was determined if the change in monthly migraine days from the 4-week baseline phase to the last 3 months (mean of months 4, 5 and 6) of the 24-week double-blind treatment phase * 100 / baseline monthly migraine days was less than or equal to -50%.	4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase
Secondary	Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days to the Last 3 Months of the Double-blind Treatment Period	Monthly acute migraine-specific medication treatment days is the number of days on which migraine specific medications were used between monthly doses of study drug. Migraine-specific medications includes two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications.; 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 phase - the number of migraine-specific treatment days during the 4-week baseline phase.	4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase
Secondary	Change From Baseline in Mean Monthly Average Physical Impairment Domain Score Measured by MPFID in the Last 3 Months of the Double-blind Treatment Phase	The Migraine Physical Function Impact Diary (MPFID) is a self-administered 13-item instrument measuring physical functioning. It has two domains, Impact on Everyday Activities (7 items) and Physical Impairment (5 items), and one stand-alone global question. Participants completed the MPFID daily in an electronic diary based on the past 24 hours. Participants responded to each item on a 5-point scale, with difficulty items ranging from "Without any difficulty" (1) to "Unable to do" (5) and frequency items ranging from "None of the time" (1) to "All of the time" (5). For each domain, the scores were calculated as the sum of the responses and rescaled to 0 - 100, with higher scores representing greater impact of migraine.; Change from baseline was calculated as (mean monthly average physical impairment scores as measured by the MPFID over the last 3 months of the double-blind treatment period) - (baseline monthly average physical impairment scores as measured by the MPFID).	4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase
Secondary	Change From Baseline in Mean Monthly Average Impact on Everyday Activities Score Measured by MPFID in the Last 3 Months of the Double-blind Treatment Phase	The Migraine Physical Function Impact Diary (MPFID) is a self-administered 13-item instrument measuring physical functioning. It has two domains, Impact on Everyday Activities (7 items) and Physical Impairment (5 items), and one stand-alone global question. Participants completed the MPFID daily in an electronic diary based on the past 24 hours. Participants responded to each item on a 5-point scale, with difficulty items ranging from "Without any difficulty" (1) to "Unable to do" (5) and frequency items ranging from "None of the time" (1) to "All of the time" (5). For each domain, the scores were calculated as the sum of the responses and rescaled to 0 - 100, with higher scores representing greater impact of migraine.; Change from baseline was calculated as (mean monthly impact on everyday activities scores as measured by the MPFID over the last 3 months of the double-blind treatment period) - (baseline monthly impact on everyday activities scores as measured by the MPFID).	4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase

External Links

•   AmgenTrials clinical trials website