A Study of Galcanezumab (LY2951742) in Participants With Episodic Migraine (PERSIST)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Galcanezumab in Patients With Episodic Migraine-the Persist Study

The reason for this study is to see if the drug galcanezumab is safe and effective in participants with episodic migraine. The study will last about 53 weeks and may include up to 12 visits.

Study Overview

• Status: Completed
• Conditions: Episodic Migraine
• Intervention / Treatment: Drug: Placebo; Drug: Galcanezumab

• Study Type: Interventional
• Enrollment (Actual): 520
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Chinese PLA General Hospital
    • Beijing, Beijing, China, 100053
      • Xuanwu Hospital-Capital Medical University
  • Chongqing
    • Chongqing, Chongqing, China, 400016
      • The First Affiliated Hospital Chongqing Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510180
      • Guangzhou First People's Hospital
  • Guizhou
    • Guiyang, Guizhou, China, 550004
      • The affiliated Hospital of Guiyang Medical College
  • Henan
    • Zhengzhou, Henan, China, 450052
      • The First Affiliated Hospital of Zhengzhou Universtiy
  • Hubei
    • Wu Han, Hubei, China, 430030
      • Tongji Hosp Tongji Med Col Huazhong Univ of Sci & Tech
    • Wuhan, Hubei, China, 430022
      • Wuhan Union Hospital
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital, Central South University
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • The First Affliated Hospital of Soochow University
    • Zhenjiang, Jiangsu, China, 212000
      • Affiliated Hospital of Jiangsu University
  • Jiangxi
    • Pingxiang, Jiangxi, China, 337000
      • Pingxiang People's Hospital
  • Jilin
    • Changchun City, Jilin, China, 130041
      • No.2 Hospital Affiliated to Jilin University
  • Jinnan District
    • Tianjin, Jinnan District, China, 300350
      • Tianjin Huanhu Hospital
  • Nanjing
    • Nanjing, Nanjing, China, 210029
      • Jiangsu Province Hospital
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • First Affiliated Hospital of Xi'an Jiaotong University
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
    • Rizhao, Shandong, China, 276826
      • People's Hospital of Rizhao
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital, Fudan University
    • Shanghai, Shanghai, China, 20040
      • Huashan Hospital affiliated to Fudan University
    • Shanghai, Shanghai, China, 20000
      • Shanghai East Hospital
  • Sichuan
    • Cheng Du, Sichuan, China, 610041
      • West China Hospital Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • First Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310013
      • Zhejiang Hospital
  • Zizhiqu
    • Baotou, Zizhiqu, China, 014040
      • Bao Tou Central Hospital
• India
  • New Delhi, India, 110002
    • Gobind Ballabh Pant Hospital
  • Delhi
    • New Delhi, Delhi, India, 110060
      • Sir Ganga Ram Hospital
    • New Delhi, Delhi, India, 110029
      • All India Institute of Medical Sciences
  • Gujarat
    • Ahmedabad, Gujarat, India, 382428
      • Apollo Hospitals International Ltd.
  • Haryana
    • Gurgaon, Haryana, India, 122001
      • Artemis Hospital
  • Karnataka
    • Mangalore, Karnataka, India, 575003
      • Mangala Hospitals & Mangala Kidney Foundation
  • Madh Prad
    • Indore, Madh Prad, India, 452008
      • CHL - Apollo Hospital
  • Maharashtra
    • Nagpur, Maharashtra, India, 440012
      • Getwell Hospital & Research Institute
    • Nashik, Maharashtra, India, 422001
      • HCG Manavata Cancer Centre
    • Pune, Maharashtra, India, 411004
      • Deenanath Mangeshkar Hospital & Research Centre
• Russian Federation
  • Moscow, Russian Federation, 119991
    • First Moscow State Medical University n.a. Sechenov
  • Moscow, Russian Federation, 121467
    • University Headache Clinic
  • Nizhny Novgorod, Russian Federation, 603137
    • OOO "Medis"
  • St-Petersburg, Russian Federation, 197022
    • Academician I.P. Pavlov First St-Petersburg State Medical University

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:

• Participants must have a diagnosis of migraine as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 (1.1 or 1.2) (ICHD-3 2018) with a history of migraine of at least 1 year prior to screening and migraine onset prior to age 50
• Prior to screening, participants must have a history of 4-14 migraine headache days and at least 2 migraine attacks per month on average within the past 3 months

Exclusion Criteria:

• Are currently enrolled in any other clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study
• Current use or prior exposure to galcanezumab or another calcitonin gene-related peptide (CGRP) antibody, including those who have previously completed or withdrawn from this study or any other study investigating a CGRP antibody
• Participants who are taking, or are expected to take, therapeutic antibodies during the course of the study (for example, adalimumab, infliximab, trastuzumab, bevacizumab, etc.)
• Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic proteins, or to galcanezumab
• Women who are pregnant or nursing
• History of chronic migraine, daily persistent headache, cluster headache, medication overuse headache, migraine with brainstem aura, or hemiplegic migraine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Double-blind treatment phase: Participants received placebo once per month subcutaneously (SC) for 3 months.; Open-label treatment phase: After completion of double-blind phase, participants could enter open-label treatment phase where they received 240 milligram (mg) loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.; Follow-up phase: After completion or discontinuation from double-blind or open-label treatment phases, participants entered follow-up phase where they were observed for 4 months. No treatments administered.	Drug: Placebo; Administered SC
Experimental: Galcanezumab 120 mg; Double-blind treatment phase: Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.; Open-label treatment phase: After completion of double-blind phase, participants could enter open-label treatment phase where they continued to receive 120 mg galcanezumab SC per month for 3 months.; Follow-up phase: After completion or discontinuation from double-blind or open-label treatment phases, participants entered follow-up phase where they were observed for 4 months. No treatments administered.	Drug: Galcanezumab; Administered SC; Other Names: LY2951742

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days (MHDs) During the Double-blind Treatment Phase.	MHD is a calendar day on which a migraine or probable migraine (a headache missing 1 of the migraine features) occurred. Per International Headache Society [IHS] International Classification of Headache Disorders 3rd edition [ICHD-3], migraine is defined as a headache, with or without aura, of ≥30 minutes duration with the following required features (A) At least 2 of the following headache characteristics: Unilateral location; Pulsatile quality; Moderate or severe pain intensity; Aggravation by or causing avoidance of routine physical activity (B) During headache at least 1 of the following: Nausea and/or vomiting; Photophobia and phonophobia. Overall mean is derived from the average of months 1 to 3 with Least square (LS) mean change calculated using mixed model repeat measures (MMRM) model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.	Baseline, 3 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Mean Percentage of Participants With ≥30%, ≥50%, ≥75%, 100% Reduction From Baseline in Monthly Migraine Headache Days (MHDs) During the Double-blind Treatment Phase.	Participant having: 30% or greater reduction in the total number of MHDs relative to baseline in a 30-day period is considered to have 30% response rate to treatment or "30% responder."; 50% or greater reduction in the total number of MHDs relative to baseline in a 30-day period is considered to have 50% response rate to treatment or "50% responder."; 75% or greater reduction in the total number of MHDs relative to baseline in a 30-day period is considered to have 75% response rate to treatment or "75% responder."; 100% reduction in the total number of MHDs relative to baseline in a 30-day period is considered to have 100% response rate to treatment or "100% responder." Overall mean is derived from the average of months 1 to 3 using generalized linear mixed model (GLIMMIX) with the fixed categorical effects of treatment, month, and treatment-by-month interaction, as well as the continuous, fixed covariate of baseline value.	3 Months
Overall Mean Change From Baseline in the Role Function-Restrictive Domain Score of the Migraine-Specific Quality-of-Life Questionnaire Version 2.1 (MSQ v2.1) During the Double-blind Treatment Phase.	MSQ v2.1 is a self-administered instrument that was developed to address physical, emotional limitations of specific concern to individuals with migraine. It consists of 14 items that address 3 domains: Role Function-Restrictive (items 1-7), Role Function- Preventive (items 8-11) and Emotional Function (items 12-14). All item responses ranges from 1 (none of the time) to 6 (all of the time). Total raw scores for each domain is the sum of the raw scores of each item in that domain. After the total raw score is computed for each domain, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.	Baseline, 3 Months
Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Headache During the Double-blind Treatment Phase.	Number of monthly migraine headache days requiring medication for the acute treatment of headache is defined as the number of calendar days in a 30-day period on which migraine or probable migraine occurs and acute medication is used. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.	Baseline, 3 Months
Overall Mean Change From Baseline in the Number of Monthly Headache Days During the Double-blind Treatment Phase.	Number of monthly headache days is the number of calendar days in a 30-day period on which a headache occurs. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.	Baseline, 3 Months
Percentage of Participants Who Maintain 50% Response Criteria During the Double-blind Treatment Phase.	Percentage of participants who maintained 50% response rate to treatment in all 3 months of the double-blind treatment phase.	Month 1 to Month 3
Overall Mean Change From Baseline in Number of Monthly Migraine Attacks During the Double-blind Treatment Phase.	Number of monthly migraine attacks is the number of sets of consecutive days with migraine or probable migraine separated by at least one migraine-free day in a 30-day period day. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.	Baseline, 3 Months
Overall Mean Change From Baseline in Number of Monthly Migraine Headache Hours During the Double-blind Treatment Phase.	Number of monthly migraine headache hours is the total number of headache hours in a 30-day period on days when a migraine or probable migraine occurs. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.	Baseline, 3 Months
Overall Mean Change From Baseline in Number of Monthly Headache Hours During the Double-blind Treatment Phase.	Number of monthly headache hours is the total number of headache hours in a 30-day period on which a headache occurred. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.	Baseline, 3 Months
Overall Mean Change From Baseline in Severity of Migraine Headaches During the Double-blind Treatment Phase.	Severity of Migraine Headache was measured on a headache severity scale ranging from 1 to 3 with 1=mild, 2=moderate, and 3=severe. The mean severity of migraine headache for each month will be calculated as: sum of severity of migraine headache days divided by number of migraine headache days. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.	Baseline, 3 Months
Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S) Score at Month 3 During the Double-blind Treatment Phase.	PGI-S is a 7-point scale that measures participants own global impression of their illness severity. The participant was instructed as follows: "Considering migraine as a chronic condition, how would you rate your level of illness?" Response options range from 1 ("normal, not at all ill") to 7 ("extremely ill"). LS mean change was calculated using analysis of variance (ANCOVA) model with fixed categorical effects of treatment, country, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.	Baseline, Month 3
Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score at Month 3 During the Double-blind Treatment Phase.	The MIDAS was designed to quantify headache-related disability over a 3-month period. This instrument consists of 5 items that measures the impact that migraine headaches have on migraineurs' life, including days of work/school missed, days with productivity at work/school reduced to half or more, days with household work missed, days with productivity in household work reduced to half or more, and days missed family/social/leisure activities. Each item has a numeric response range from 0 to 90 days; if days are missed from work/school or household work they are not counted as days with reduced productivity at work/school or household work. The numeric responses are summed to produce a total score ranging from 0 to 270. A higher value is indicative of more disability. LS mean change was calculated using ANCOVA model with fixed categorical effects of treatment, country, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.	Baseline, Month 3
Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA) During the Double-blind Treatment Phase.	A TE-ADA evaluable participant is considered to be TE-ADA positive 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 positive if there is at least one post baseline result of ADA Present with titer >= 20.	Baseline to Month 3
Pharmacokinetics (PK): Serum Concentration of Galcanezumab During the Double-blind Treatment Phase.	PK: Serum concentration of galcanezumab	Month 3

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Hu B, Li G, Li X, Wu S, Yu T, Li X, Zhao H, Jia Z, Zhuang J, Yu S. Galcanezumab in episodic migraine: the phase 3, randomized, double-blind, placebo-controlled PERSIST study. J Headache Pain. 2022 Jul 28;23(1):90. doi: 10.1186/s10194-022-01458-0.

Helpful Links

• A Study of Galcanezumab (LY2951742) in Participants With Episodic Migraine

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2019
• Primary Completion (Actual): July 27, 2021
• Study Completion (Actual): March 11, 2022

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: May 23, 2019
• First Posted (Actual): May 24, 2019

Study Record Updates

• Last Update Posted (Actual): March 28, 2023
• Last Update Submitted That Met QC Criteria: March 1, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: prevention; prophylactic
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: 17054; I5Q-MC-CGAX (Other Identifier: Eli Lilly and Company)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes