Clinical trial NCT02614183: Evaluation of Galcanezumab in the Prevention of Episodic Migraine- the EVOLVE-1 Study
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients With Episodic Migraine - the EVOLVE-1 Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Migraine
Keywords: prevention
prophylaxis
headache
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2015-11-25
Enrollment: 862
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the efficacy of the study drug known as galcanezumab in participants with episodic migraine.


Eligibility criteria: Inclusion Criteria:

* Have a diagnosis of episodic migraine as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta guidelines (1.1 or 1.2) (ICHD-3 2013), with a history of migraine headaches of at least 1 year prior to screening, migraine onset prior to age 50 and MONTHLY frequency of 4-14 Migraine Headache Days (MHD).

Exclusion Criteria:

* Are currently enrolled in or have participated within the last 30 days or within 5 half-lives (whichever is longer) in a clinical trial involving an investigational product.
* Current use or prior exposure to Galcanezumab or another CGRP antibody.
* Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic proteins, or to Galcanezumab.
* History of persistent daily headache, cluster headache or migraine subtypes including hemiplegic (sporadic or familial) migraine, ophthalmoplegic migraine, and migraine with brainstem aura (basilar-type migraine) defined by IHS ICHD-3 beta.

Primary outcomes:
measure: Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days
timeFrame: Baseline, Month 1 through Month 6
Secondary outcomes:
measure: Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75% and 100% in Monthly Migraine Headache Days
timeFrame: Baseline, Month 1 through Month 6
measure: Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 (v2.1) Role Function Restrictive Domain
timeFrame: Baseline, Month 4 through Month 6
measure: Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache
timeFrame: Baseline, Month 1 through Month 6
measure: Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S) Rating
timeFrame: Baseline, Month 4 through Month 6
measure: Overall Mean Change From Baseline in Headache Hours
timeFrame: Baseline, Month 1 through Month 6
measure: Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score
timeFrame: Baseline, Month 6
measure: Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab
timeFrame: Month 1 through Month 6
measure: Pharmacokinetics (PK): Serum Concentrations of Galcanezumab
timeFrame: Month 6
measure: Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)
timeFrame: Month 6
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Territory Neurology & Research Institute
state: Arizona
city: Tucson
country: United States
facility: Orange Grove Family Practice
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Clinical Research
state: Arkansas
city: Carmichael
country: United States
facility: Advanced Clinical Research
state: California
city: Encino
country: United States
facility: Pharmacology Research Institute, Newport Beach
state: California
city: Encino
country: United States
facility: Tooraj Joseph Raoof M.D., Inc.
state: California
city: Fullerton
country: United States
facility: Fullerton Neurology and Headache Center
state: California
city: Imperial
country: United States
facility: Sun Valley Research Center
state: California
city: Irvine
country: United States
facility: Irvine Clinical Research Center
state: California
city: Los Alamitos
country: United States
facility: Pharmacology Research Institute, Newport Beach
state: California
city: Newport Beach
country: United States
facility: Pharmacology Research Institute, Newport Beach
state: California
city: Rancho Mirage
country: United States
facility: Desert Valley Research
state: California
city: Redlands
country: United States
facility: Anderson Clinical Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: San Diego
country: United States
facility: Medical Center for Clinical Research
state: California
city: Boulder
country: United States
facility: Alpine Clinical Research Center
state: Colorado
city: Colorado Springs
country: United States
facility: MCB Clinical Research Centers
state: Colorado
city: Denver
country: United States
facility: Mile High Research Center
state: Colorado
city: Englewood
country: United States
facility: Colorado Neurological Institute
state: Colorado
city: Fort Collins
country: United States
facility: Advanced Neurosciences Research, LLC
state: Colorado
city: Waterbury
country: United States
facility: Chase Medical Research, LLC
state: Connecticut
city: Bradenton
country: United States
facility: Meridien Research
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Ocoee
country: United States
facility: Sensible Healthcare
state: Florida
city: Orlando
country: United States
facility: Psychiatric Inst of Florida-Clinical Neuroscience Solutions
state: Florida
city: Oviedo
country: United States
facility: Compass Research
state: Florida
city: Port Orange
country: United States
facility: Accord Clinical Research, LLC
state: Florida
city: Sarasota
country: United States
facility: Roskamp Institute
state: Florida
city: Sunrise
country: United States
facility: Infinity Clinical Reserach . LLC
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute at Palm Beach Neurology
state: Florida
city: Meridian
country: United States
facility: Advanced Clinical Research LLC
state: Idaho
city: Blue Island
country: United States
facility: Healthcare Research Network - Blue Island
state: Illinois
city: Anderson
country: United States
facility: Community Clinical Research Center
state: Indiana
city: Elwood
country: United States
facility: Investigative Clinical Research of Indiana, LLC
state: Indiana
city: Indianapolis
country: United States
facility: Midwest Institute for Clinical Research
state: Indiana
city: Newburgh
country: United States
facility: Deaconess Clinic Inc
state: Indiana
city: West Des Moines
country: United States
facility: Integrated Clinical Trial Services, Inc.
state: Iowa
city: Prairie Village
country: United States
facility: Phoenix Medical Research, Inc
state: Kansas
city: Edgewood
country: United States
facility: Otri-Med Corporation
state: Kentucky
city: Louisville
country: United States
facility: L-Marc Research Center
state: Kentucky
city: Baltimore
country: United States
facility: PharmaSite Research Inc
state: Maryland
city: Boston
country: United States
facility: Boston Clinical Trials Inc
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Head, Pain and Neurological Institute
state: Michigan
city: Minneapolis
country: United States
facility: Clinical Research Institute
state: Minnesota
city: Springfield
country: United States
facility: ClinVest
state: Missouri
city: Nashua
country: United States
facility: Healthy Perspectives Innovative Mental Health Services, PL
state: New Hampshire
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials
state: New Mexico
city: Amherst
country: United States
facility: Dent Neurological Institute
state: New York
city: Manlius
country: United States
facility: Central New York Clinical Research
state: New York
city: New York
country: United States
facility: NYU Langone
state: New York
city: New York
country: United States
facility: Fieve Clincial Services
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc.
state: New York
city: Charlotte
country: United States
facility: Metrolina Neurological Associates, PA
state: North Carolina
city: Greensboro
country: United States
facility: Headache Wellness Center
state: North Carolina
city: Cleveland
country: United States
facility: Rapid Medical Research Inc
state: Ohio
city: Toledo
country: United States
facility: Medical College of Ohio at Toledo
state: Ohio
city: Tulsa
country: United States
facility: Healthcare Research Consultant
state: Oklahoma
city: Portland
country: United States
facility: Summit Research Network Inc
state: Oregon
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians
state: Pennsylvania
city: Willow Grove
country: United States
facility: Abington Neurological Associates
state: Pennsylvania
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Charleston
country: United States
facility: Clinical Trials of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: 8 Medical Park
state: South Carolina
city: Chattanooga
country: United States
facility: ClinSearch
state: Tennessee
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Clinical Research Associates
state: Tennessee
city: Austin
country: United States
facility: FutureSearch Trials
state: Texas
city: Hurst
country: United States
facility: Protenium Clinical Research
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: San Antonio
country: United States
facility: Radiant Research - San Antonio
state: Texas
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
city: Charlottesville
country: United States
facility: Charlottesville Medical Research
state: Virginia
city: Norfolk
country: United States
facility: Clinical Research Associates of Tidewater
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research - Richmond
state: Virginia
city: Spokane
country: United States
facility: Premier Clinical Research
state: Washington
city: Vancouver
country: United States
facility: Vancouver Clinic
state: Washington
city: Kenosha
country: United States
facility: Clinical Investigation Specialists Inc
state: Wisconsin
city: Brampton
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
city: Kelowna
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
city: Mississauga
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
city: Montreal
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
city: Ottawa
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
city: Sherbrooke
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
city: Toronto
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
city: Vancouver
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
city: Waterloo
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
city: Manati
country: Puerto Rico
facility: Office of Dr. Ruddy Guerra
city: Rio Piedras
country: Puerto Rico
facility: NuFrontiers Clinical Research LLC
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico, Inc.
city: San Juan
country: Puerto Rico
facility: GCM Medical Group PSC
city: San Juan
country: Puerto Rico
facility: Instituto de Neurologia Dra. Ivonne Fraga
city: San Juan
country: Puerto Rico
facility: Neuro GI Wellness Center
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Ailani J, Kuruppu DK, Rettiganti M, Oakes T, Schroeder K, Wietecha L, Port M, Blumenfeld AM. Does "wearing off" of efficacy occur in galcanezumab-treated patients at the end of the monthly treatment cycle? Post hoc analyses of four phase III randomized trials. Headache. 2022 Feb;62(2):198-207. doi: 10.1111/head.14257. Epub 2022 Jan 25.
citation: Citrome L, Sanchez Del Rio M, Dong Y, Nichols RM, Tockhorn-Heidenreich A, Foster SA, Stauffer VL. Benefit-Risk Assessment of Galcanezumab Versus Placebo for the Treatment of Episodic and Chronic Migraine Using the Metrics of Number Needed to Treat and Number Needed to Harm. Adv Ther. 2021 Aug;38(8):4442-4460. doi: 10.1007/s12325-021-01848-x. Epub 2021 Jul 15.
citation: Jedynak J, Eross E, Gendolla A, Rettiganti M, Stauffer VL. Shift from high-frequency to low-frequency episodic migraine in patients treated with Galcanezumab: results from two global randomized clinical trials. J Headache Pain. 2021 May 28;22(1):48. doi: 10.1186/s10194-021-01222-w.
citation: Pozo-Rosich P, Samaan KH, Schwedt TJ, Nicholson RA, Rettiganti M, Pearlman EM. Galcanezumab Provides Consistent Efficacy Throughout the Dosing Interval Among Patients with Episodic and Chronic Migraine: A Post Hoc Analysis. Adv Ther. 2021 Jun;38(6):3154-3165. doi: 10.1007/s12325-021-01708-8. Epub 2021 May 5.
citation: Ament M, Day K, Stauffer VL, Skljarevski V, Rettiganti M, Pearlman E, Aurora SK. Effect of galcanezumab on severity and symptoms of migraine in phase 3 trials in patients with episodic or chronic migraine. J Headache Pain. 2021 Feb 6;22(1):6. doi: 10.1186/s10194-021-01215-9.
citation: Kuruppu DK, North JM, Kovacik AJ, Dong Y, Pearlman EM, Hutchinson SL. Onset, Maintenance, and Cessation of Effect of Galcanezumab for Prevention of Migraine: A Narrative Review of Three Randomized Placebo-Controlled Trials. Adv Ther. 2021 Mar;38(3):1614-1626. doi: 10.1007/s12325-021-01632-x. Epub 2021 Feb 5.
citation: Dodick DW, Doty EG, Aurora SK, Ruff DD, Stauffer VL, Jedynak J, Dong Y, Pearlman EM. Medication overuse in a subgroup analysis of phase 3 placebo-controlled studies of galcanezumab in the prevention of episodic and chronic migraine. Cephalalgia. 2021 Mar;41(3):340-352. doi: 10.1177/0333102420966658. Epub 2020 Nov 3.
citation: Ailani J, Andrews JS, Rettiganti M, Nicholson RA. Impact of galcanezumab on total pain burden: findings from phase 3 randomized, double-blind, placebo-controlled studies in patients with episodic or chronic migraine (EVOLVE-1, EVOLVE-2, and REGAIN trials). J Headache Pain. 2020 Oct 17;21(1):123. doi: 10.1186/s10194-020-01190-7.
citation: Stauffer VL, Turner I, Kemmer P, Kielbasa W, Day K, Port M, Quinlan T, Camporeale A. Effect of age on pharmacokinetics, efficacy, and safety of galcanezumab treatment in adult patients with migraine: results from six phase 2 and phase 3 randomized clinical trials. J Headache Pain. 2020 Jun 23;21(1):79. doi: 10.1186/s10194-020-01148-9.
citation: Bangs ME, Kudrow D, Wang S, Oakes TM, Terwindt GM, Magis D, Yunes-Medina L, Stauffer VL. Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies. BMC Neurol. 2020 Jan 17;20(1):25. doi: 10.1186/s12883-020-1609-7.
citation: Kielbasa W, Quinlan T. Population Pharmacokinetics of Galcanezumab, an Anti-CGRP Antibody, Following Subcutaneous Dosing to Healthy Individuals and Patients With Migraine. J Clin Pharmacol. 2020 Feb;60(2):229-239. doi: 10.1002/jcph.1511. Epub 2019 Sep 4.
citation: Silberstein SD, Stauffer VL, Day KA, Lipsius S, Wilson MC. Galcanezumab in episodic migraine: subgroup analyses of efficacy by high versus low frequency of migraine headaches in phase 3 studies (EVOLVE-1 & EVOLVE-2). J Headache Pain. 2019 Jun 28;20(1):75. doi: 10.1186/s10194-019-1024-x.
citation: Stauffer VL, Wang S, Voulgaropoulos M, Skljarevski V, Kovacik A, Aurora SK. Effect of Galcanezumab Following Treatment Cessation in Patients With Migraine: Results From 2 Randomized Phase 3 Trials. Headache. 2019 Jun;59(6):834-847. doi: 10.1111/head.13508. Epub 2019 Apr 3.
citation: Forderreuther S, Zhang Q, Stauffer VL, Aurora SK, Lainez MJA. Preventive effects of galcanezumab in adult patients with episodic or chronic migraine are persistent: data from the phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2, and REGAIN studies. J Headache Pain. 2018 Dec 29;19(1):121. doi: 10.1186/s10194-018-0951-2.
citation: Nichols R, Doty E, Sacco S, Ruff D, Pearlman E, Aurora SK. Analysis of Initial Nonresponders to Galcanezumab in Patients With Episodic or Chronic Migraine: Results From the EVOLVE-1, EVOLVE-2, and REGAIN Randomized, Double-Blind, Placebo-Controlled Studies. Headache. 2019 Feb;59(2):192-204. doi: 10.1111/head.13443. Epub 2018 Nov 21.
citation: Stauffer VL, Dodick DW, Zhang Q, Carter JN, Ailani J, Conley RR. Evaluation of Galcanezumab for the Prevention of Episodic Migraine: The EVOLVE-1 Randomized Clinical Trial. JAMA Neurol. 2018 Sep 1;75(9):1080-1088. doi: 10.1001/jamaneurol.2018.1212.