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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02614183
Recruitment Status : Completed
First Posted : November 25, 2015
Results First Posted : November 29, 2018
Last Update Posted : June 17, 2020
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Migraine
Interventions Drug: Galcanezumab
Drug: Placebo
Enrollment 862
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Galcanezumab 120mg Galcanezumab 240mg
Hide Arm/Group Description Participants (pts) received placebo by subcutaneous injection once a month for 6 months. Participants did not receive any intervention during post-treatment follow-up phase. Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection. Participants did not receive any intervention during post-treatment follow-up phase. Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months. Participants did not receive any intervention during post-treatment follow-up phase.
Period Title: Double Blind Treatment Phase
Started 434 214 214
Received at Least One Dose of Study Drug 433 213 212
Safety Population 432 206 [1] 220 [2]
Completed 351 177 175
Not Completed 83 37 39
Reason Not Completed
Adverse Event             10             9             7
Lack of Efficacy             10             1             2
Lost to Follow-up             18             9             5
Physician Decision             7             3             2
Pregnancy             2             1             3
Protocol Violation             2             2             2
Withdrawal by Subject             33             11             16
Did not receive study drug             1             1             2
[1]
One pt randomized to placebo received galcanezumab 120mg due to dosing error moved to this group.
[2]
Eight pts discontinued after loading dose of 240mg galcanezumab in 120mg group moved to this group.
Period Title: Post Treatment Follow-up Phase
Started 372 [1] 185 [1] 183 [1]
Safety Population 372 183 185 [2]
Completed 354 179 171
Not Completed 18 6 12
Reason Not Completed
Lost to Follow-up             5             3             5
Physician Decision             5             1             2
Protocol Violation             1             0             0
Withdrawal by Subject             7             2             5
[1]
Participants who discontinued double blind phase had an option to enter post-treatment phase.
[2]
Two participants who received only 240mg loading dose prior to discontinuation moved to this group.
Arm/Group Title Placebo Galcanezumab 120mg Galcanezumab 240mg Total
Hide Arm/Group Description Participants received placebo by subcutaneous injection once a month for 6 months. Participants did not receive any intervention during post-treatment follow-up phase. Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection. Participants did not receive any intervention during post-treatment follow-up phase. Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months. Participants did not receive any intervention during post-treatment follow-up phase. Total of all reporting groups
Overall Number of Baseline Participants 433 213 212 858
Hide Baseline Analysis Population Description
All randomized participants who received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 433 participants 213 participants 212 participants 858 participants
41.33  (11.40) 40.93  (11.87) 39.07  (11.52) 40.67  (11.57)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 433 participants 213 participants 212 participants 858 participants
Female 362 181 175 718
Male 71 32 37 140
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 433 participants 213 participants 212 participants 858 participants
Hispanic or Latino 58 27 37 122
Not Hispanic or Latino 359 180 171 710
Unknown or Not Reported 16 6 4 26
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 433 participants 213 participants 212 participants 858 participants
American Indian or Alaska Native 0 0 3 3
Asian 13 7 4 24
Native Hawaiian or Other Pacific Islander 1 0 2 3
Black or African American 42 29 23 94
White 356 169 165 690
More than one race 21 8 15 44
Unknown or Not Reported 0 0 0 0
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 433 participants 213 participants 212 participants 858 participants
Canada 44 20 21 85
Puerto Rico 11 5 4 20
United States 378 188 187 753
Migraine Headache Days (MHD) per month   [1] 
Mean (Standard Deviation)
Unit of measure:  Days per Month
Number Analyzed 433 participants 213 participants 212 participants 858 participants
9.08  (2.97) 9.21  (3.05) 9.14  (2.91) 9.13  (2.97)
[1]
Measure Description: Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred.
1.Primary Outcome
Title Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days
Hide Description

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.

Time Frame Baseline, Month 1 through Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.
Arm/Group Title Placebo Galcanezumab 120mg Galcanezumab 240mg
Hide Arm/Group Description:
Participants received placebo by subcutaneous injection once a month for 6 months.
Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.
Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Overall Number of Participants Analyzed 425 210 208
Least Squares Mean (Standard Error)
Unit of Measure: Days
-2.81  (0.24) -4.73  (0.29) -4.57  (0.29)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 120mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.92
Confidence Interval (2-Sided) 95%
-2.48 to -1.37
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.28
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 240mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.76
Confidence Interval (2-Sided) 95%
-2.31 to -1.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.28
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mean Percentage of Participants With Reduction From Baseline ≥50%, ≥75% and 100% in Monthly Migraine Headache Days
Hide Description

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.

Time Frame Baseline, Month 1 through Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.
Arm/Group Title Placebo Galcanezumab 120mg Galcanezumab 240mg
Hide Arm/Group Description:
Participants received placebo by subcutaneous injection once a month for 6 months.
Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.
Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Overall Number of Participants Analyzed 425 210 208
Mean (Standard Error)
Unit of Measure: percentage of participants
≥50% 38.6  (1.7) 62.3  (2.4) 60.9  (2.5)
≥75% 19.3  (1.4) 38.8  (2.4) 38.5  (2.4)
100% 6.2  (0.8) 15.6  (1.6) 14.6  (1.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 120mg
Comments Reduction from Baseline ≥50%
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.63
Confidence Interval (2-Sided) 95%
2.05 to 3.37
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 240mg
Comments Reduction from Baseline ≥50%
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.48
Confidence Interval (2-Sided) 95%
1.94 to 3.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 120mg
Comments Reduction from Baseline ≥75%
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.65
Confidence Interval (2-Sided) 95%
2.04 to 3.45
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 240mg
Comments Reduction from Baseline ≥75%
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.62
Confidence Interval (2-Sided) 95%
2.01 to 3.41
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 120mg
Comments Reduction from Baseline = 100%
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.80
Confidence Interval (2-Sided) 95%
1.96 to 4.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 240mg
Comments Reduction from Baseline = 100%
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.61
Confidence Interval (2-Sided) 95%
1.81 to 3.75
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ) Version 2.1 (v2.1) Role Function Restrictive Domain
Hide Description

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.

Time Frame Baseline, Month 4 through Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.
Arm/Group Title Placebo Galcanezumab 120mg Galcanezumab 240mg
Hide Arm/Group Description:
Participants received placebo by subcutaneous injection once a month for 6 months.
Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.
Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Overall Number of Participants Analyzed 419 207 202
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
24.69  (1.07) 32.43  (1.31) 32.09  (1.32)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 120mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.74
Confidence Interval (2-Sided) 95%
5.20 to 10.28
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 240mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.40
Confidence Interval (2-Sided) 95%
4.83 to 9.97
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.31
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Migraine or Headache
Hide Description

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.

Time Frame Baseline, Month 1 through Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had baseline and post baseline value.
Arm/Group Title Placebo Galcanezumab 120mg Galcanezumab 240mg
Hide Arm/Group Description:
Participants received placebo by subcutaneous injection once a month for 6 months.
Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.
Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Overall Number of Participants Analyzed 425 210 208
Least Squares Mean (Standard Error)
Unit of Measure: Days
-2.15  (0.21) -3.96  (0.25) -3.76  (0.26)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 120mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.81
Confidence Interval (2-Sided) 95%
-2.28 to -1.33
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.24
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 240mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value -1.61
Confidence Interval (2-Sided) 95%
-2.09 to -1.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.26
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S) Rating
Hide Description 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.
Time Frame Baseline, Month 4 through Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had baseline and post baseline value.
Arm/Group Title Placebo Galcanezumab 120mg Galcanezumab 240mg
Hide Arm/Group Description:
Participants received placebo by subcutaneous injection once a month for 6 months.
Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.
Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Overall Number of Participants Analyzed 419 207 202
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.27  (0.08) -1.59  (0.10) -1.55  (0.10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 120mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.32
Confidence Interval (2-Sided) 95%
-0.52 to -0.12
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 240mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.48 to -0.07
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.10
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Overall Mean Change From Baseline in Headache Hours
Hide Description 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.
Time Frame Baseline, Month 1 through Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.
Arm/Group Title Placebo Galcanezumab 120mg Galcanezumab 240mg
Hide Arm/Group Description:
Participants received placebo by subcutaneous injection once a month for 6 months.
Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.
Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Overall Number of Participants Analyzed 425 210 208
Least Squares Mean (Standard Error)
Unit of Measure: Hours per Month
-15.67  (2.24) -29.65  (2.70) -29.31  (2.72)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 120mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -13.98
Confidence Interval (2-Sided) 95%
-18.99 to -8.97
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.55
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 240mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -13.64
Confidence Interval (2-Sided) 95%
-18.68 to -8.60
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.57
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score
Hide Description

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.

Time Frame Baseline, Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.
Arm/Group Title Placebo Galcanezumab 120mg Galcanezumab 240mg
Hide Arm/Group Description:
Participants received placebo by subcutaneous injection once a month for 6 months.
Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.
Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Overall Number of Participants Analyzed 389 195 189
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-14.87  (1.37) -21.16  (1.65) -20.06  (1.68)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 120mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.29
Confidence Interval (2-Sided) 95%
-9.45 to -3.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.61
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 240mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.19
Confidence Interval (2-Sided) 95%
-8.39 to -1.98
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.63
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants Developing Anti-drug Antibodies (ADA) to Galcanezumab
Hide Description 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.
Time Frame Month 1 through Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had least one non-missing test result for ADA for each of the baseline period and the post-baseline period.
Arm/Group Title Placebo Galcanezumab 120mg Galcanezumab 240mg
Hide Arm/Group Description:
Participants received placebo by subcutaneous injection once a month for 6 months.
Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.
Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Overall Number of Participants Analyzed 422 202 213
Measure Type: Number
Unit of Measure: percentage of participants
TE ADA+ 1.66 3.47 5.16
Neutralizing Antibodies 1.42 3.47 5.16
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 120mg
Comments TE ADA Positive.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.160
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 240mg
Comments TE ADA Positive.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .020
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 120mg
Comments Neutralizing Antibodies.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .131
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Galcanezumab 240mg
Comments Neutralizing Antibodies.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .009
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
9.Secondary Outcome
Title Pharmacokinetics (PK): Serum Concentrations of Galcanezumab
Hide Description Pharmacokinetics (PK): Serum Concentrations of Galcanezumab.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had measurable serum concentrations.
Arm/Group Title Galcanezumab 120mg Galcanezumab 240mg
Hide Arm/Group Description:
Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.
Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months.
Overall Number of Participants Analyzed 156 149
Mean (Standard Deviation)
Unit of Measure: Nanogram per milliliter (ng/mL)
15400  (8340) 29500  (12300)
10.Secondary Outcome
Title Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)
Hide Description Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP).
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had received at least one dose of study drug and had measurable plasma concentrations.
Arm/Group Title Placebo Galcanezumab 120mg Galcanezumab 240mg
Hide Arm/Group Description:
Participants received placebo by subcutaneous injection once a month for 6 months.
Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.
Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months
Overall Number of Participants Analyzed 28 165 158
Mean (Standard Deviation)
Unit of Measure: ng/mL
0.888  (1.89) 4.25  (1.79) 5.13  (2.43)
Time Frame Up to 10 Months
Adverse Event Reporting Description

All-Cause Mortality:All participants (pts) who received atleast 1 dose of study drug.

SAE/AE:Eight pts discontinued after receiving loading dose (LD) of 240mg galcanezumab (GAL) in 120mg group (gp) moved to 240mg treatment gp. One pt randomized to placebo received GAL 120mg due to dosing error moved to 120mg treatment gp. Two pts who received only 240mg LD prior to discontinuation moved to 240mg post-treatment gp. There are gender specific adverse events only occurring in male or female pts.

 
Arm/Group Title Placebo - Treatment Phase Galcanezumab 120mg - Treatment Phase Galcanezumab 240mg - Treatment Phase Placebo - Post-Treatment Phase Galcanezumab 120mg - Post-Treatment Phase Galcanezumab 240mg - Post-Treatment Phase
Hide Arm/Group Description Participants received placebo by subcutaneous injection once a month for 6 months. Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection. Participants received 240mg galcanezumab by subcutaneous injection once a month for 6 months. Participants didn't receive any intervention. Participants didn't receive any intervention. Participants didn't receive any intervention.
All-Cause Mortality
Placebo - Treatment Phase Galcanezumab 120mg - Treatment Phase Galcanezumab 240mg - Treatment Phase Placebo - Post-Treatment Phase Galcanezumab 120mg - Post-Treatment Phase Galcanezumab 240mg - Post-Treatment Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/433 (0.00%)      0/213 (0.00%)      0/212 (0.00%)      0/372 (0.00%)      0/185 (0.00%)      0/183 (0.00%)    
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Placebo - Treatment Phase Galcanezumab 120mg - Treatment Phase Galcanezumab 240mg - Treatment Phase Placebo - Post-Treatment Phase Galcanezumab 120mg - Post-Treatment Phase Galcanezumab 240mg - Post-Treatment Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/432 (1.16%)      6/206 (2.91%)      0/220 (0.00%)      2/372 (0.54%)      4/183 (2.19%)      4/185 (2.16%)    
Cardiac disorders             
Cardiac failure congestive  1  0/432 (0.00%)  0 0/206 (0.00%)  0 0/220 (0.00%)  0 0/372 (0.00%)  0 0/183 (0.00%)  0 1/185 (0.54%)  1
Cardiomyopathy  1  0/432 (0.00%)  0 0/206 (0.00%)  0 0/220 (0.00%)  0 0/372 (0.00%)  0 0/183 (0.00%)  0 1/185 (0.54%)  1
Ear and labyrinth disorders             
Inner ear disorder  1  0/432 (0.00%)  0 0/206 (0.00%)  0 0/220 (0.00%)  0 0/372 (0.00%)  0 0/183 (0.00%)  0 1/185 (0.54%)  1
Gastrointestinal disorders             
Pancreatitis acute  1  0/432 (0.00%)  0 1/206 (0.49%)  1 0/220 (0.00%)  0 0/372 (0.00%)  0 0/183 (0.00%)  0 0/185 (0.00%)  0
Small intestinal obstruction  1  0/432 (0.00%)  0 1/206 (0.49%)  1 0/220 (0.00%)  0 0/372 (0.00%)  0 0/183 (0.00%)  0 0/185 (0.00%)  0
Vomiting  1  0/432 (0.00%)  0 0/206 (0.00%)  0 0/220 (0.00%)  0 0/372 (0.00%)  0 1/183 (0.55%)  1 0/185 (0.00%)  0
General disorders             
Asthenia  1  0/432 (0.00%)  0 0/206 (0.00%)  0 0/220 (0.00%)  0 1/372 (0.27%)  1 0/183 (0.00%)  0 0/185 (0.00%)  0
Hepatobiliary disorders             
Cholelithiasis  1  2/432 (0.46%)  2 0/206 (0.00%)  0 0/220 (0.00%)  0 0/372 (0.00%)  0 0/183 (0.00%)  0 0/185 (0.00%)  0
Injury, poisoning and procedural complications             
Incarcerated incisional hernia  1  0/432 (0.00%)  0 1/206 (0.49%)  1 0/220 (0.00%)  0 0/372 (0.00%)  0 0/183 (0.00%)  0 0/185 (0.00%)  0
Ligament rupture  1  0/432 (0.00%)  0 1/206 (0.49%)  1 0/220 (0.00%)  0 0/372 (0.00%)  0 0/183 (0.00%)  0 0/185 (0.00%)  0
Seroma  1  0/432 (0.00%)  0 1/206 (0.49%)  1 0/220 (0.00%)  0 0/372 (0.00%)  0 0/183 (0.00%)  0 0/185 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Tendonitis  1  0/432 (0.00%)  0 1/206 (0.49%)  1 0/220 (0.00%)  0 0/372 (0.00%)  0 0/183 (0.00%)  0 0/185 (0.00%)  0
Vertebral osteophyte  1  1/432 (0.23%)  1 0/206 (0.00%)  0 0/220 (0.00%)  0 0/372 (0.00%)  0 0/183 (0.00%)  0 0/185 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Tonsil cancer  1  0/432 (0.00%)  0 0/206 (0.00%)  0 0/220 (0.00%)  0 0/372 (0.00%)  0 1/183 (0.55%)  1 0/185 (0.00%)  0
Tubular breast carcinoma  1  0/432 (0.00%)  0 1/206 (0.49%)  1 0/220 (0.00%)  0 0/372 (0.00%)  0 0/183 (0.00%)  0 0/185 (0.00%)  0
Uterine leiomyoma  1  0/361 (0.00%)  0 0/175 (0.00%)  0 0/182 (0.00%)  0 0/311 (0.00%)  0 1/156 (0.64%)  1 0/156 (0.00%)  0
Pregnancy, puerperium and perinatal conditions             
Abortion missed  1  0/361 (0.00%)  0 0/175 (0.00%)  0 0/182 (0.00%)  0 0/311 (0.00%)  0 0/156 (0.00%)  0 1/156 (0.64%)  1
Pre-eclampsia  1  0/361 (0.00%)  0 0/175 (0.00%)  0 0/182 (0.00%)  0 0/311 (0.00%)  0 1/156 (0.64%)  1 0/156 (0.00%)  0
Psychiatric disorders             
Adjustment disorder with mixed anxiety and depressed mood  1  0/432 (0.00%)  0 0/206 (0.00%)  0 0/220 (0.00%)  0 0/372 (0.00%)  0 0/183 (0.00%)  0 1/185 (0.54%)  1
Renal and urinary disorders             
Ureterolithiasis  1  0/432 (0.00%)  0 0/206 (0.00%)  0 0/220 (0.00%)  0 1/372 (0.27%)  1 0/183 (0.00%)  0 0/185 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Pulmonary embolism  1  1/432 (0.23%)  1 0/206 (0.00%)  0 0/220 (0.00%)  0 0/372 (0.00%)  0 0/183 (0.00%)  0 0/185 (0.00%)  0
Vascular disorders             
Deep vein thrombosis  1  1/432 (0.23%)  1 0/206 (0.00%)  0 0/220 (0.00%)  0 0/372 (0.00%)  0 0/183 (0.00%)  0 0/185 (0.00%)  0
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo - Treatment Phase Galcanezumab 120mg - Treatment Phase Galcanezumab 240mg - Treatment Phase Placebo - Post-Treatment Phase Galcanezumab 120mg - Post-Treatment Phase Galcanezumab 240mg - Post-Treatment Phase
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   129/432 (29.86%)      63/206 (30.58%)      72/220 (32.73%)      22/372 (5.91%)      12/183 (6.56%)      12/185 (6.49%)    
General disorders             
Injection site pain  1  75/432 (17.36%)  365 33/206 (16.02%)  158 45/220 (20.45%)  212 0/372 (0.00%)  0 0/183 (0.00%)  0 0/185 (0.00%)  0
Injection site reaction  1  4/432 (0.93%)  11 7/206 (3.40%)  14 12/220 (5.45%)  20 0/372 (0.00%)  0 0/183 (0.00%)  0 0/185 (0.00%)  0
Infections and infestations             
Upper respiratory tract infection  1  31/432 (7.18%)  36 9/206 (4.37%)  11 15/220 (6.82%)  18 12/372 (3.23%)  14 6/183 (3.28%)  6 5/185 (2.70%)  5
Urinary tract infection  1  15/432 (3.47%)  15 8/206 (3.88%)  9 13/220 (5.91%)  13 8/372 (2.15%)  8 3/183 (1.64%)  3 0/185 (0.00%)  0
Viral upper respiratory tract infection  1  29/432 (6.71%)  31 19/206 (9.22%)  23 8/220 (3.64%)  9 3/372 (0.81%)  3 3/183 (1.64%)  3 7/185 (3.78%)  7
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
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Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
EMail: ClinicalTrials.gov@lilly.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02614183    
Other Study ID Numbers: 15767
I5Q-MC-CGAG ( Other Identifier: Eli Lilly and Company )
First Submitted: November 23, 2015
First Posted: November 25, 2015
Results First Submitted: October 8, 2018
Results First Posted: November 29, 2018
Last Update Posted: June 17, 2020