Treatment for Prevention of Chronic Migraine Clinical Trial
Official title:
A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Chronic Migraine Prevention
| Verified date | October 2022 |
| Source | Amgen |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
To evaluate the effect of erenumab compared to placebo on the change from baseline in the number of monthly migraine days in adults with chronic migraine.
| Status | Completed |
| Enrollment | 667 |
| Est. completion date | April 28, 2016 |
| Est. primary completion date | February 24, 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 65 Years |
| Eligibility | Inclusion Criteria: - History of at least 5 attacks of migraine without aura and/or migraine with visual sensory, speech and/or language, retinal or brainstem aura. - History of = 15 headache days per month of which = 8 headache days were assessed by the subject as migraine day. - = 4 distinct headache episodes, each lasting = 4 hours OR if shorter, associated with use of a triptan or ergot-derivative on the same calendar day based on the eDiary calculations. - Demonstrated at least 80% compliance with the eDiary. Exclusion Criteria: - History of cluster headache or hemiplegic migraine headache - Unable to differentiate migraine from other headaches - Failed > 3 medication categories due to lack of efficacy for prophylactic treatment of migraine . - Received botulinum toxinin head or neck region within 4 months prior to screening. - Used a prohibited migraine prophylactic medication, device or procedure within 2 months prior to the start of the baseline phase |
| Country | Name | City | State |
|---|---|---|---|
| Canada | Research Site | Calgary | Alberta |
| Canada | Research Site | Montreal | Quebec |
| Czechia | Research Site | Brno | |
| Czechia | Research Site | Brno | |
| Czechia | Research Site | Praha 2 | |
| Czechia | Research Site | Praha 4 | |
| Denmark | Research Site | Glostrup | |
| Finland | Research Site | Helsinki | |
| Finland | Research Site | Jyväskylä | |
| Finland | Research Site | Oulu | |
| Finland | Research Site | Tampere | |
| Finland | Research Site | Turku | |
| Germany | Research Site | Berlin | |
| Germany | Research Site | Berlin | |
| Germany | Research Site | Bochum | |
| Germany | Research Site | Essen | |
| Germany | Research Site | Hamburg | |
| Germany | Research Site | Kiel | |
| Germany | Research Site | Königstein im Taunus | |
| Norway | Research Site | Ålesund | |
| Norway | Research Site | Lillehammar | |
| Norway | Research Site | Sandvika | |
| Norway | Research Site | Stavanger | |
| Poland | Research Site | Krakow | |
| Poland | Research Site | Lodz | |
| Poland | Research Site | Lublin | |
| Poland | Research Site | Poznan | |
| Poland | Research Site | Swidnik | |
| Poland | Research Site | Warszawa | |
| Poland | Research Site | Warszawa | |
| Poland | Research Site | Warszawa | |
| Sweden | Research Site | Falköping | |
| Sweden | Research Site | Stockholm | |
| Sweden | Research Site | Stockholm | |
| Sweden | Research Site | Stockholm | |
| Sweden | Research Site | Vällingby | |
| United Kingdom | Research Site | Glasgow | |
| United Kingdom | Research Site | Hull | |
| United Kingdom | Research Site | London | |
| United Kingdom | Research Site | Stoke on Trent | |
| United States | Research Site | Amherst | New York |
| United States | Research Site | Ann Arbor | Michigan |
| United States | Research Site | Atlanta | Georgia |
| United States | Research Site | Austin | Texas |
| United States | Research Site | Cleveland | Ohio |
| United States | Research Site | Dallas | Texas |
| United States | Research Site | Dallas | Texas |
| United States | Research Site | Decatur | Georgia |
| United States | Research Site | Greensboro | North Carolina |
| United States | Research Site | Indianapolis | Indiana |
| United States | Research Site | Jacksonville | Florida |
| United States | Research Site | Kalamazoo | Michigan |
| United States | Research Site | La Jolla | California |
| United States | Research Site | Milwaukee | Wisconsin |
| United States | Research Site | Nashville | Tennessee |
| United States | Research Site | Newport Beach | California |
| United States | Research Site | Orlando | Florida |
| United States | Research Site | Palm Beach Gardens | Florida |
| United States | Research Site | Philadelphia | Pennsylvania |
| United States | Research Site | Pikesville | Maryland |
| United States | Research Site | Reno | Nevada |
| United States | Research Site | Saint Louis | Missouri |
| United States | Research Site | San Francisco | California |
| United States | Research Site | Santa Monica | California |
| United States | Research Site | Seattle | Washington |
| United States | Research Site | Sherman Oaks | California |
| United States | Research Site | Springfield | Missouri |
| United States | Research Site | Stamford | Connecticut |
| United States | Research Site | Stanford | California |
| United States | Research Site | Temple | Texas |
| United States | Research Site | Virginia Beach | Virginia |
| United States | Research Site | Watertown | Massachusetts |
| United States | Research Site | West Palm Beach | Florida |
| United States | Research Site | Worcester | Massachusetts |
| Lead Sponsor | Collaborator |
|---|---|
| Amgen |
United States, Canada, Czechia, Denmark, Finland, Germany, Norway, Poland, Sweden, United Kingdom,
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
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.
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, Burstein R, Buse DC, Dodick DW, Koukakis R, Klatt J, Cheng S, Chou DE. Efficacy of erenumab in chronic migraine patients with and without ictal allodynia. Cephalalgia. 2021 Oct;41(11-12):1152-1160. doi: 10.1177/03331024211010305. Epub 2021 May 13. — 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
Lipton RB, Tepper SJ, Reuter U, Silberstein S, Stewart WF, Nilsen J, Leonardi DK, Desai P, Cheng S, Mikol DD, Lenz R. Erenumab in chronic migraine: Patient-reported outcomes in a randomized double-blind study. Neurology. 2019 May 7;92(19):e2250-e2260. doi: 10.1212/WNL.0000000000007452. Epub 2019 Apr 17. — View Citation
Lipton RB, Tepper SJ, Silberstein SD, Kudrow D, Ashina M, Reuter U, Dodick DW, Zhang F, Rippon GA, Cheng S, Mikol DD. Reversion from chronic migraine to episodic migraine following treatment with erenumab: Results of a post-hoc analysis of a randomized, 12-week, double-blind study and a 52-week, open-label extension. Cephalalgia. 2021 Jan;41(1):6-16. doi: 10.1177/0333102420973994. Epub 2020 Dec 3. — View Citation
Tepper S, Ashina M, Reuter U, Brandes JL, Doležil D, Silberstein S, Winner P, Leonardi D, Mikol D, Lenz R. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017 Jun;16(6):425-434. doi: 10.1016/S1474-4422(17)30083-2. Epub 2017 Apr 28. — View Citation
Tepper SJ, Diener HC, Ashina M, Brandes JL, Friedman DI, Reuter U, Cheng S, Nilsen J, Leonardi DK, Lenz RA, Mikol DD. Erenumab in chronic migraine with medication overuse: Subgroup analysis of a randomized trial. Neurology. 2019 May 14;92(20):e2309-e2320. doi: 10.1212/WNL.0000000000007497. Epub 2019 Apr 17. — 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
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change From Baseline in Monthly Migraine Days | 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 number of migraine days during the last 4 weeks of the 12-week 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 treatment phase | |
| Secondary | Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Baseline | 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. Monthly migraine days were calculated as the number of migraine days in the 4-week baseline phase and during the last 4 weeks of treatment. 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 4 weeks of the 12-week treatment phase * 100 / baseline monthly migraine days was less than or equal to -50%. |
4-week baseline phase and the last 4 weeks of the 12-week treatment phase | |
| Secondary | Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days | 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. | 4-week baseline phase and the last 4 weeks of the 12-week treatment phase | |
| Secondary | Change From Baseline in Cumulative Monthly Headache Hours | The cumulative duration of any qualified headache between monthly doses of study drug regardless of acute treatment use. A qualified headache was defined as follows: a qualified migraine headache (including an aura-only event that is treated with acute migraine-specific medication), or a qualified non-migraine headache, which is a headache that lasted continuously for = 4 hours and was not a qualified migraine headache, or a headache of any duration for which acute headache treatment was administered. |
4-week baseline phase and the last 4 weeks of the 12-week treatment phase | |
| Secondary | Number of Participants With Adverse Events | Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4, where: Grade 1 = Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2 = Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL; Grade 4 = Life-threatening consequences; urgent intervention indicated Grade 5 = Death related to AE. |
From the first dose of study drug up to 16 weeks after the last dose (24 weeks) | |
| Secondary | Number of Participants Who Developed Antibodies to Erenumab | Blood samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect anti-drug antibodies (ADA) against erenumab. Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based bioassay to determine neutralizing activity against erenumab (Neutralizing Antibody Assay). Developing antibody incidence indicates participants with a negative or no result at baseline and a positive result at any time post-baseline. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies. |
Baseline and weeks 2, 4, 8, 12 and 24 |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02174861 -
A Study to Assess the Long-term Safety and Efficacy of Erenumab (AMG 334) in Chronic Migraine Prevention.
|
Phase 2 |