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Evaluation of Efficay & Safety of Galcanezumab in the Prevention of Episodic Migraine- the EVOLVE-2 Study

Phase 3
Completed
Conditions
Migraine
Interventions
Drug: Placebo
Registration Number
NCT02614196
Lead Sponsor
Eli Lilly and Company
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
986
Inclusion Criteria
  • Have a diagnosis of migraine as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta version (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 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 Calcitonin Gene-Related Peptide (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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo given by SC injection once a month for 6 months.
Placebo Maximum Extended Enrollment CohortPlaceboPlacebo given by SC injection once a month for 6 months.
Galcanezumab 240mg Maximum Extended Enrollment CohortGalcanezumabGalcanezumab 240mg given by SC injection once a month for 6 months.
Galcanezumab 120mgGalcanezumabGalcanezumab 240mg given as loading dose at first dosing visit followed by galcanezumab 120mg once a month for 5 months by subcutaneous (SC) injection.
Galcanezumab 240mgGalcanezumabGalcanezumab 240mg given by SC injection once a month for 6 months.
Galcanezumab 120mg Maximum Extended Enrollment CohortGalcanezumabGalcanezumab 240mg given as loading dose at first dosing visit followed by galcanezumab 120mg once a month for 5 months by subcutaneous (SC) injection.
Primary Outcome Measures
NameTimeMethod
Overall Mean Change From Baseline in the Number of Monthly Migraine Headache DaysBaseline, Month 1 through Month 6

Migraine Headache Day (MHD):A calendar day on which a migraine headache or probable migraine headache occurred.

Migraine Headache : A headache, with or without aura, of ≥30 minutes duration with both of the following required features (A and B):

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; AND B) During headache at least one of the following: Nausea and/or vomiting; Photophobia and phonophobia;

Overall mean is derived from the average of months 1 to 6 from mixed model repeated measures (MMRM) model. Least Square (LS) mean was calculated using mixed model repeated measures (MMRM) model with treatment, pooled country, month, and treatment by month, baseline, and baseline by month as fixed effects.

Secondary Outcome Measures
NameTimeMethod
Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75%, and 100% in Monthly Migraine Headache DaysBaseline, Month 1 through Month 6

Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred.

Mean is derived from the average of months 1 to 6 from generalized linear mixed model repeated measures. Mean percentages of participants were calculated with a generalized linear mixed model repeated measures method with treatment, month and treatment by month, baseline.

Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 Role Function Restrictive DomainBaseline, Month 4 through Month 6

MSQ v2.1 was developed to address physical \& emotional limitations of specific concern to individuals with migraine.

It consists of 14 items that address 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 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.

Mean is derived from the average of months 4 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline by month \& baseline MHD category as fixed factors.

Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or HeadacheBaseline, Month 1 through Month 6

Migraine Headache Day (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 6 from MMRM model.LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed effects.

Mean Change From Baseline in Patient Global Impression of Severity (PGI-S) RatingBaseline, Month 4 through Month 6

The PGI-S scale is a participant-rated instrument that measures patients 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 were from 1 ("normal, not at all ill") to 7 ("extremely ill"). Mean is derived from the average of months 4 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed factors.

Overall Mean Change From Baseline in Headache HoursBaseline, Month 1 through Month 6

Headache Hours is calculated as the total number of headache hours on which a headache occurred. Overall mean is derived from the average of months 1 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month and baseline MHD category.

Mean Change From Baseline in the Migraine Disability Assessment Test (MIDAS) Total ScoreBaseline, Month 6

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.

LSMean was calculated using MMRM model with treatment, pooled country, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed factors.

Percentage of Participants Developing Anti-drug Antibodies (ADA) to GalcanezumabMonth 1 through Month 6

Treatment emergent (TE) ADA evaluable participant is considered to be TE ADA+ if the subject 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.

Pharmacokinetics (PK): Serum Concentrations of GalcanezumabMonth 6

Pharmacokinetics (PK): Serum Concentrations of Galcanezumab.

Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)Month 6

Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP).

Trial Locations

Locations (53)

Neurology & Neuroscience Associates, Inc.

🇺🇸

Akron, Ohio, United States

Catalina Research Institute, LLC

🇺🇸

Montclair, California, United States

Axiom Research

🇺🇸

Apple Valley, California, United States

Pacific Research Partners, LLC

🇺🇸

Oakland, California, United States

IMMUNOe International Research Centers

🇺🇸

Centennial, Colorado, United States

Clinical Research of South Florida

🇺🇸

Coral Gables, Florida, United States

Clinical Neuroscience Solutions Inc

🇺🇸

Jacksonville, Florida, United States

Sensible Healthcare

🇺🇸

Ocoee, Florida, United States

Christie Clinic, LLC

🇺🇸

Champaign, Illinois, United States

Novex Clinical Research

🇺🇸

New Bedford, Massachusetts, United States

Healthcare Research Network - Hazelwood

🇺🇸

Hazelwood, Missouri, United States

Heartland Research Associates

🇺🇸

Wichita, Kansas, United States

Bio Behavioral Health

🇺🇸

Toms River, New Jersey, United States

Albuquerque Clinical Trials

🇺🇸

Albuquerque, New Mexico, United States

Regional Clinical Research

🇺🇸

Binghamton, New York, United States

High Point Clinical Trials Center

🇺🇸

High Point, North Carolina, United States

SPRI Clinical Trials, LLC.

🇺🇸

Brooklyn, New York, United States

Urgent Care Specialists, LLC

🇺🇸

Dayton, Ohio, United States

Oregon Neurology Associates

🇺🇸

Springfield, Oregon, United States

Mountain View Clinical Research, Inc

🇺🇸

Greer, South Carolina, United States

FutureSearch Trials

🇺🇸

Dallas, Texas, United States

Clinpoint Trial, LLC

🇺🇸

Waxahachie, Texas, United States

Coastal Carolina Research Center, Inc.

🇺🇸

Mount Pleasant, South Carolina, United States

Jordan River Family Medicine

🇺🇸

South Jordan, Utah, United States

Hillel Yaffe

🇮🇱

Hadera, Israel

Health Research of Hampton Roads Inc

🇺🇸

Newport News, Virginia, United States

Northwest Clinical Research Center

🇺🇸

Bellevue, Washington, United States

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.

🇬🇧

Stoke-on-Trent, United Kingdom

Dean Foundation for Health Research and Education

🇺🇸

Middleton, Wisconsin, United States

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

🇰🇷

Seoul, Korea, Republic of

Cortex, PSC

🇵🇷

Las Piedras, Puerto Rico

SomniCare Sleep Institute

🇵🇷

San Juan, Puerto Rico

Cedars Sinai Medical Center

🇺🇸

Los Angeles, California, United States

Atlanta Center of Medical Research

🇺🇸

Atlanta, Georgia, United States

Clinical Research of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Polyclinic

🇺🇸

Seattle, Washington, United States

Medical Center for Clinical Research

🇺🇸

San Diego, California, United States

Diamond Headache Clinic

🇺🇸

Chicago, Illinois, United States

Josephson Wallack Munshower Neurology

🇺🇸

Indianapolis, Indiana, United States

Sentara Neurology Specialists

🇺🇸

Virginia Beach, Virginia, United States

Sunrise Clinical Research

🇺🇸

Hollywood, Florida, United States

Univ of Cincinnati College of Medicine

🇺🇸

Cincinnati, Ohio, United States

QUEST Research Institute

🇺🇸

Farmington Hills, Michigan, United States

Nevada Headache Institute

🇺🇸

Las Vegas, Nevada, United States

Clinical Trial Network

🇺🇸

Houston, Texas, United States

21st Century Neurology

🇺🇸

Phoenix, Arizona, United States

Arizona Research Center

🇺🇸

Phoenix, Arizona, United States

Optimus Medical Group

🇺🇸

San Francisco, California, United States

IPS Research Company

🇺🇸

Oklahoma City, Oklahoma, United States

Foothill Family Clinic

🇺🇸

Salt Lake City, Utah, United States

Schuster Medical Research Institute

🇺🇸

Sherman Oaks, California, United States

Westside Center for Clinical Research

🇺🇸

Jacksonville, Florida, United States

Meridien Research

🇺🇸

Tampa, Florida, United States

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