Evaluation of Galcanezumab in the Prevention of Episodic Migraine- the EVOLVE-1 Study

Phase 3

Completed

Conditions: Migraine

Interventions: Drug: Placebo
Drug: Galcanezumab

Registration Number: NCT02614183

Lead Sponsor: Eli Lilly and Company

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 862

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo given by SC injection once a month for 6 months.
Galcanezumab 240mg	Galcanezumab	Galcanezumab 240mg given by SC injection once a month for 6 months.
Galcanezumab 120mg	Galcanezumab	Galcanezumab given by subcutaneous (SC) injection at 120mg dose once a month for 6 months. Participants received a loading dose of 240mg (2 injections of 120mg each) was administered at visit 3 only.

Primary Outcome Measures

Name	Time	Method
Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days	Baseline, 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

Name	Time	Method
Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)	Month 6	Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP).
Overall Mean Change From Baseline in Headache Hours	Baseline, 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 on the Migraine Disability Assessment Test (MIDAS) Total Score	Baseline, 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.
Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 (v2.1) Role Function Restrictive Domain	Baseline, 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.
Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab	Month 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.
Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75% and 100% in Monthly Migraine Headache Days	Baseline, 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.
Pharmacokinetics (PK): Serum Concentrations of Galcanezumab	Month 6	Pharmacokinetics (PK): Serum Concentrations of Galcanezumab.
Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache	Baseline, 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 the Patient Global Impression of Severity (PGI-S) Rating	Baseline, Month 4 through Month 6	The PGI-S scale is a patient-rated instrument that measures patients own global impression of their illness severity. The patient 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.

Trial Locations

Locations (84): Territory Neurology & Research Institute
🇺🇸
Tucson, Arizona, United States
Orange Grove Family Practice
🇺🇸
Tucson, Arizona, United States
Arkansas Clinical Research
🇺🇸
Little Rock, Arkansas, United States
Advanced Clinical Research
🇺🇸
West Jordan, Utah, United States
Pharmacology Research Institute, Newport Beach
🇺🇸
Newport Beach, California, United States
Tooraj Joseph Raoof M.D., Inc.
🇺🇸
Encino, California, United States
Fullerton Neurology and Headache Center
🇺🇸
Fullerton, California, United States
Sun Valley Research Center
🇺🇸
Imperial, California, United States
Irvine Clinical Research Center
🇺🇸
Irvine, California, United States
Desert Valley Research
🇺🇸
Rancho Mirage, California, United States
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Territory Neurology & Research Institute
🇺🇸Tucson, Arizona, United States