A Safety Study of Galcanezumab in Participants With Migraine, With or Without Aura

A Phase 3, Long-Term, Open-Label Safety Study of LY2951742 in Patients With Migraine

The main purpose of this study is to evaluate the longer term safety of the study drug known as galcanezumab in participants with episodic or chronic migraine.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Galcanezumab

• Study Type: Interventional
• Enrollment (Actual): 270
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brugge, Belgium, 8000
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Brussel, Belgium, 1090
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Liege, Belgium, 4000
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Canada
  • Calgary, Canada, T3M 1M4
    • 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.
  • Sherbrooke, Canada, J1H1Z1
    • 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.
  • Toronto, Canada, M4S 1Y2
    • 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.
• France
  • Marseille, France, 13385
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Nice, France, 6000
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Paris, France, 75010
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Saint Etienne, France, 42055
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Hungary
  • Budapest, Hungary, 1083
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Esztergom, Hungary, 2500
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Gyor, Hungary, 9023
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Ponce School of Medicine CAIMED Center
• United States
  • California
    • Santa Monica, California, United States, 90404
      • California Medical Clinic for Headache
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • New England Institute for Clinical Research
  • Florida
    • Hollywood, Florida, United States, 33021
      • Sunrise Clinical Research
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Mercy Health Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Albuquerque Neurosciences
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Wilmington, North Carolina, United States, 28401
      • Wilmington Health Associates
  • Pennsylvania
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Associates
  • Texas
    • Waxahachie, Texas, United States, 75165
      • Clinpoint Trial, LLC
  • Utah
    • Clinton, Utah, United States, 84015
      • Ericksen Research and Development
  • Virginia
    • Roanoke, Virginia, United States, 24018
      • Blue Ridge Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have a diagnosis of episodic or chronic migraine as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta guidelines (1.1, 1.2 or 1.3) (ICHD-3 2013), with a history of migraine headaches of at least 1 year prior to screening, and migraine onset prior to age 50.
• Prior to baseline, a history of 4 or more migraine headache days per month on average for the past 3 months.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Galcanezumab 120 mg; Galcanezumab 240mg given as loading dose at first dosing visit followed by 120 mg given by subcutaneous (SC) injection once a month for up to 11 months by auto injector or pre-filled syringe.	Drug: Galcanezumab; Administered SC; Other Names: LY2951742
EXPERIMENTAL: Galcanezumab 240 mg; Galcanezumab 240 mg given by SC injection once a month for up to 12 months by auto injector or pre-filled syringe.	Drug: Galcanezumab; Administered SC; Other Names: LY2951742

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Discontinued Due to Adverse Event	Adverse Event: Any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A summary of other non-serious AEs, and all SAE's, regardless of causality, is reported in the Adverse Events section.	Baseline through Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Galcanezumab	Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Galcanezumab	Baseline through Month 12
Serum Concentrations of Galcanezumab	Serum Concentrations of Galcanezumab.	Month 12
Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)	Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)	Month 12
Percentage of Participants Developing Anti-Drug Antibodies to Galcanezumab	A Treatment Emergent Anti-drug Antibody (TE ADA) evaluable participant is considered to be TE ADA+ if the participant has at least one post-baseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the participant is TE ADA+ if there is at least one post-baseline result of ADA Present with titer >= 1: 20 (treatment-induced). There were 6 participants in the 120 mg arm who discontinued after receiving loading dose of 240mg, these participants were moved to 240mg arm for safety analysis.	Month 1 through Month 12
Overall Mean Change From Baseline in the Number of Migraine Headache Days (MHD)	MHD: A calendar day on which a migraine headache or probable migraine headache occurred. Overall mean is derived from the average of months 1 to 12 from MMRM model. Least squares mean (LSMean) was calculated using mixed model repeated measures (MMRM) model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month as fixed effects.	Baseline, Month 1 through Month 12
Overall Mean Change From Baseline in the Number of Headache Days	Headache Day: A calendar day on which any type of headache occurred (including migraine, probable migraine, and non-migraine headache). Overall mean is derived from the average of months 1 to 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month as fixed effects.	Baseline, Month 1 through Month 12
Percentage of Participants With Overall Reduction From Baseline ≥50% in Monthly Migraine Headache Days	Migraine Headache Day: A calendar day on which a migraine headache or probable migraine headache occurred. Overall percentage of participants with a given response rate were estimated from the generalized linear mixed models (GLIMMIX) model.	Baseline, Month 1 through Month 12
Overall Mean Change From Baseline in the Frequency of Medication Use for the Acute Treatment of Migraines or Headaches	Overall mean is derived from the average of months 1 to 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month as fixed effects.	Baseline, Month 1 through Month 12
Overall Mean Patient Global Impression-Improvement (PGI-I) Score	The Patient Global Impression of Improvement (PGI -I) scale is a participant-rated instrument that measures the participants own global impression of their symptom improvement. The participant was instructed as follows: "Mark the box that best describes your migraine headache condition since you started taking this medicine." Response options were on a 7-point scale in which a score of 1 indicates that the participant's condition is "very much better," a score of 4 indicates that the participant has experienced "no change," and a score of 7 indicates that the participant is "very much worse." Overall mean is derived from the average of months 1 to 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline PGI-S, and baseline PGI-S by month as fixed effects.	Month 1 through Month 12
Overall Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score	The MIDAS is a participant-rated scale which was designed to quantify headache-related disability over a 3-month period. This instrument consists of five items that reflect the number of days reported as missing or with reduced productivity at work or home, and the number of days of missed social events. Each item has a numeric response range from 0 to 90 days, if days are missed from work or home they are not counted as days with reduced productivity at work or home. The numeric responses are summed to produce a total score ranging from 0 to 270, in which a higher value is indicative of more disability. Overall mean is derived from the average of months 1 to 12 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled investigative site, month, and treatment by month, baseline, and baseline by month.	Baseline, Month 1 through Month 12
Overall Mean Change From Baseline on the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1	MSQv2.1 is a health status instrument,with a 4-week recall period, developed to address physical & emotional limitations of specific concern to individuals with migraine. Addressing the impact of migraine on work or daily activities, relationships with family & friends, leisure time, productivity, concentration, energy, tiredness & feelings.It consists of 14 items addressing 3 domains:(1)Role Function-Restrictive (items 1-7);(2)Role Function- Preventive (items 8-11);&(3)Emotional Function (items 12-14).Response options range from "none of the time" (value 1) to "all of the time" (value 6), & are reverse-recoded (value 6 to 1) before the domain scores are calculated. Total raw scores for each domain is the sum of the final item value for all of the items in that domain.After total raw score is computed for each domain & total score, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement.	Baseline, Month 1 through Month 12
Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M)	The PSMQ-M is a self-rated scale which measures participants level of satisfaction with study medication.The scale has been modified for use in this study, assessing 3 items related to the clinical trial treatment over the past 4 weeks: satisfaction, preference, and side effects. Satisfaction responses range from "very unsatisfied" to "very satisfied" with the current treatment. Preference compares the current study medication to previous medications, with responses from "much rather prefer my previous medication" to "much rather prefer the medication administered to me during the study".	Baseline through Month 12
Number of Participant Visits With Positive Reponses by Device Type Subcutaneous Administration Assessment Questionnaire Q1, Q3-Q12	The SQAAQ is a self-administered questionnaire that provides an assessment of ease of use and confidence with using a device to administer a subcutaneous injection of study drug. Participants will respond to questionnaire items using a 7-point Likert scale (from "Strongly Disagree" to "Strongly Agree") shortly after the injection. If a caregiver administers the injection, the participants should be prepared to provide the caregiver's ratings of the questions.strongly agree & agree are considered as positive responses.	Baseline through Month 12

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• 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.
• 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.
• 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. Erratum In: BMC Neurol. 2020 Mar 13;20(1):90.
• Camporeale A, Kudrow D, Sides R, Wang S, Van Dycke A, Selzler KJ, Stauffer VL. A phase 3, long-term, open-label safety study of Galcanezumab in patients with migraine. BMC Neurol. 2018 Nov 9;18(1):188. doi: 10.1186/s12883-018-1193-2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 30, 2015
• Primary Completion (ACTUAL): May 12, 2017
• Study Completion (ACTUAL): August 14, 2018

Study Registration Dates

• First Submitted: November 23, 2015
• First Submitted That Met QC Criteria: November 23, 2015
• First Posted (ESTIMATE): November 25, 2015

Study Record Updates

• Last Update Posted (ACTUAL): June 17, 2020
• Last Update Submitted That Met QC Criteria: June 10, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: prevention; prophylaxis; headache
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: 15770; I5Q-MC-CGAJ (OTHER: Eli Lilly and Company); 2015-001884-38 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR