Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Migraine Prevention (STRIVE)

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: NCT02456740
Recruitment Status : Completed
First Posted : May 28, 2015
Results First Posted : July 10, 2018
Last Update Posted : November 29, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Migraine
Interventions Drug: Erenumab
Drug: Placebo
Enrollment 955
Recruitment Details

This study was conducted at 121 centers in Canada, Austria, Belgium, Czech Republic, Finland, Germany, Poland, Slovakia, Sweden, the United Kingdom, Turkey, the Netherlands and USA.

The study consisted of a 24-week double-blind treatment phase and a 28-week active treatment phase.

Pre-assignment Details

At the end of the baseline phase, participants were randomized 1:1:1 to receive placebo, erenumab 70 mg, or erenumab 140 mg monthly for 24 weeks. Randomization was stratified by region and treatment status with migraine prophylactic medication.

Participants were re-randomized at week 24 to erenumab 70 mg or 140 mg for 28 weeks.

Arm/Group Title Placebo Erenumab 70 mg QM Erenumab 140 mg QM Placebo / Erenumab 70 mg Erenumab 70 mg / Erenumab 70 mg Erenumab 140 mg / Erenumab 70 mg Placebo / Erenumab 140 mg Erenumab 70 mg / Erenumab 140 mg Erenumab 140 mg / Erenumab 140 mg
Hide Arm/Group Description Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase. Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase. Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase. Participants originally randomized to receive placebo in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 70 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase. Participants originally randomized to receive erenumab 70 mg QM in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 70 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase. Participants originally randomized to receive erenumab 140 mg QM in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 70 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase. Participants originally randomized to receive placebo QM in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 140 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase. Participants originally randomized to receive erenumab 70 mg QM in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 140 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase. Participants originally randomized to receive erenumab 140 mg QM in the 24-week double-blind treatment phase were re-randomized at week 24 to receive erenumab 140 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.
Period Title: Double-blind Treatment Phase (24 Weeks)
Started 319 317 319 0 0 0 0 0 0
Received Study Drug 319 314 319 0 0 0 0 0 0
Completed 282 284 292 0 0 0 0 0 0
Not Completed 37 33 27 0 0 0 0 0 0
Reason Not Completed
Decision by Sponsor             1             1             1             0             0             0             0             0             0
Withdrawal by Subject             27             28             21             0             0             0             0             0             0
Lost to Follow-up             9             4             5             0             0             0             0             0             0
Period Title: Active Treatment Phase (Weeks 24 - 52)
Started [1] 0 0 0 138 140 143 140 140 144
Completed 0 0 0 124 123 130 131 128 126
Not Completed 0 0 0 14 17 13 9 12 18
Reason Not Completed
Protocol Specified Criteria             0             0             0             1             4             0             0             0             5
Withdrawal by Subject             0             0             0             10             11             9             8             8             9
Death             0             0             0             0             0             0             0             1             0
Lost to Follow-up             0             0             0             3             2             4             1             3             4
[1]
Fourteen participants who completed the DBTP did not continue onto the active treatment phase
Arm/Group Title Placebo Erenumab 70 mg QM Erenumab 140 mg QM Total
Hide Arm/Group Description Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase. Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase. Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase. Total of all reporting groups
Overall Number of Baseline Participants 319 317 319 955
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 319 participants 317 participants 319 participants 955 participants
41.3  (11.2) 41.1  (11.3) 40.4  (11.1) 40.9  (11.2)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 319 participants 317 participants 319 participants 955 participants
18 - 64 years
317
  99.4%
317
 100.0%
317
  99.4%
951
  99.6%
65 - 74 years
2
   0.6%
0
   0.0%
2
   0.6%
4
   0.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 319 participants 317 participants 319 participants 955 participants
Female
274
  85.9%
268
  84.5%
272
  85.3%
814
  85.2%
Male
45
  14.1%
49
  15.5%
47
  14.7%
141
  14.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 319 participants 317 participants 319 participants 955 participants
Hispanic or Latino
32
  10.0%
26
   8.2%
22
   6.9%
80
   8.4%
Not Hispanic or Latino
287
  90.0%
291
  91.8%
297
  93.1%
875
  91.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 319 participants 317 participants 319 participants 955 participants
American Indian or Alaska Native
2
   0.6%
0
   0.0%
1
   0.3%
3
   0.3%
Asian
8
   2.5%
5
   1.6%
4
   1.3%
17
   1.8%
Black or African American
24
   7.5%
24
   7.6%
18
   5.6%
66
   6.9%
Multiple
2
   0.6%
1
   0.3%
0
   0.0%
3
   0.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
1
   0.3%
1
   0.1%
White
277
  86.8%
281
  88.6%
293
  91.8%
851
  89.1%
Other
6
   1.9%
6
   1.9%
2
   0.6%
14
   1.5%
Region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 319 participants 317 participants 319 participants 955 participants
North America
158
  49.5%
159
  50.2%
160
  50.2%
477
  49.9%
Other
161
  50.5%
158
  49.8%
159
  49.8%
478
  50.1%
Treatment Status with Migraine Prophylactic Medication  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 319 participants 317 participants 319 participants 955 participants
Current migraine prophylactic treatment
8
   2.5%
6
   1.9%
7
   2.2%
21
   2.2%
Prior migraine prophylactic treatment only
119
  37.3%
119
  37.5%
120
  37.6%
358
  37.5%
No prior / current migraine prophylactic treatment
192
  60.2%
192
  60.6%
192
  60.2%
576
  60.3%
Monthly Migraine Days   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Migraine days/month
Number Analyzed 318 participants 316 participants 319 participants 953 participants
8.23  (2.51) 8.29  (2.47) 8.34  (2.48) 8.29  (2.48)
[1]
Measure Description: A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine without aura or a migraine with aura. Monthly migraine days were calculated as the number of migraine days in the 4-week baseline phase.
[2]
Measure Analysis Population Description: Participants with non-missing values
1.Primary Outcome
Title Change From Baseline in Mean Monthly Migraine Days to the Last 3 Months of the Double-blind Treatment Period
Hide Description

A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine with or without aura.

The change from baseline in monthly migraine days was calculated as the average number of migraine days per month during the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase – the number of migraine days during the 4-week baseline phase.

Time Frame 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was conducted in the efficacy analysis set which includes participants who received at least 1 dose of study drug and had at least 1 change from baseline measurement in monthly migraine days in the double-blind treatment phase.
Arm/Group Title Placebo Erenumab 70 mg QM Erenumab 140 mg QM
Hide Arm/Group Description:
Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Overall Number of Participants Analyzed 316 312 318
Least Squares Mean (Standard Error)
Unit of Measure: migraine days / month
-1.83  (0.18) -3.23  (0.18) -3.67  (0.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 70 mg QM
Comments The primary endpoint was analyzed using a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors (region and prior/current treatment with migraine prophylactic medication), and baseline value as covariates.
Type of Statistical Test Superiority
Comments The primary endpoint was tested independently for each erenumab dose at an alpha level of 0.04 for 70 mg and of 0.01 for 140 mg to maintain the type 1 error rate at an alpha level of 0.05.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.40
Confidence Interval (2-Sided) 95%
-1.88 to -0.92
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 140 mg QM
Comments The primary endpoint was analyzed using a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors (region and prior/current treatment with migraine prophylactic medication), and baseline value as covariates.
Type of Statistical Test Superiority
Comments The primary endpoint was tested independently for each erenumab dose at an alpha level of 0.04 for 70 mg and of 0.01 for 140 mg to maintain the type 1 error rate at an alpha level of 0.05.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.85
Confidence Interval (2-Sided) 95%
-2.33 to -1.37
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days in the Last 3 Months of the Double-blind Treatment Phase
Hide Description

A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined either as a migraine without aura or a migraine with aura.

At least a 50% reduction from baseline in monthly migraine days was determined if the change in monthly migraine days from the 4-week baseline phase to the last 3 months (mean of months 4, 5 and 6) of the 24-week double-blind treatment phase * 100 / baseline monthly migraine days was less than or equal to -50%.

Time Frame 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was conducted in the efficacy analysis set which includes participants who received at least 1 dose of study drug and had at least 1 change from baseline measurement in monthly migraine days in the double-blind treatment phase. Participants with missing data at months 4, 5, and 6 were counted as non-responders.
Arm/Group Title Placebo Erenumab 70 mg QM Erenumab 140 mg QM
Hide Arm/Group Description:
Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Overall Number of Participants Analyzed 316 312 318
Measure Type: Number
Unit of Measure: percentage of participants
26.6 43.3 50.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 70 mg QM
Comments Analyzed using a Cochran-Mantel-Haenszel test, stratified by the randomization stratification factors (region and prior/current treatment with migraine prophylactic medication).
Type of Statistical Test Superiority
Comments If the primary endpoint was statistically significant for the erenumab 70 mg group, using a gate-keeping strategy, the first two (first tier) secondary endpoints were tested using the Hochberg method at an alpha level of 0.04.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.13
Confidence Interval (2-Sided) 95%
1.52 to 2.98
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 140 mg QM
Comments Analyzed using a Cochran-Mantel-Haenszel test, stratified by the randomization stratification factors (region and prior/current treatment with migraine prophylactic medication).
Type of Statistical Test Superiority
Comments If the primary endpoint was statistically significant for the erenumab 140 mg group, using a gate-keeping strategy, the first two (first tier) secondary endpoints were tested using the Hochberg method at an alpha level of 0.01.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.81
Confidence Interval (2-Sided) 95%
2.01 to 3.94
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Monthly Acute Migraine-specific Medication Treatment Days to the Last 3 Months of the Double-blind Treatment Period
Hide Description

Monthly acute migraine-specific medication treatment days is the number of days on which migraine specific medications were used between monthly doses of study drug. Migraine-specific medications includes two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications.

The change from baseline in monthly acute migraine-specific treatment days was calculated as the average number of migraine-specific treatment days per month during the last 3 months of the 24-week double-blind treatment phase – the number of migraine-specific treatment days during the 4-week baseline phase.

Time Frame 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was conducted in the efficacy analysis set which includes participants who received at least 1 dose of study drug and had at least 1 change from baseline measurement in monthly acute migraine-specific treatment days in the double-blind treatment phase.
Arm/Group Title Placebo Erenumab 70 mg QM Erenumab 140 mg QM
Hide Arm/Group Description:
Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Overall Number of Participants Analyzed 316 312 318
Least Squares Mean (Standard Error)
Unit of Measure: Acute migraine-specific med days/mo
-0.20  (0.11) -1.13  (0.11) -1.61  (0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 70 mg QM
Comments Analyzed using a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors (region and prior/current treatment with migraine prophylactic medication), and baseline value as covariates.
Type of Statistical Test Superiority
Comments If the primary endpoint was statistically significant for the erenumab 70 mg group, using a gate-keeping strategy, the first two (first tier) secondary endpoints were tested using the Hochberg method at an alpha level of 0.04.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.94
Confidence Interval (2-Sided) 95%
-1.23 to -0.64
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 140 mg QM
Comments Analyzed using a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, (stratification factors region and prior/current treatment with migraine prophylactic medication), and baseline value as covariates.
Type of Statistical Test Superiority
Comments If the primary endpoint was statistically significant for the erenumab 140 mg group, using a gate-keeping strategy, the first two (first tier) secondary endpoints were tested using the Hochberg method at an alpha level of 0.01.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.42
Confidence Interval (2-Sided) 95%
-1.71 to -1.12
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Mean Monthly Average Physical Impairment Domain Score Measured by MPFID in the Last 3 Months of the Double-blind Treatment Phase
Time Frame 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was conducted in the efficacy analysis set including participants who received at least 1 dose of study drug and had at least 1 change from baseline measurement in MPFID average physical impairment domain score in the double-blind treatment phase.
Arm/Group Title Placebo Erenumab 70 mg QM Erenumab 140 mg QM
Hide Arm/Group Description:
Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Overall Number of Participants Analyzed 316 312 318
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.38  (0.40) -4.24  (0.40) -4.81  (0.40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 140 mg QM
Comments Analyzed using a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors (region and prior/current treatment with migraine prophylactic medication), and baseline value as covariates.
Type of Statistical Test Superiority
Comments If the first tier secondary endpoints were statistically significant for both erenumab doses the erenumab 140 mg group for the 2 remaining MPFID secondary endpoints was tested using the Hochberg method at a level of 0.05; If only the erenumab 70 mg group or 140 mg group showed statistical significance for the first tier secondary endpoints then the erenumab 140 group for the 2 remaining MPFID secondary endpoints was tested for significance at a level of either 0.04 or 0.01 respectively.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.43
Confidence Interval (2-Sided) 95%
-3.51 to -1.35
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 70 mg QM
Comments Analyzed using a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors (region and prior/current treatment with migraine prophylactic medication), and baseline value as covariates.
Type of Statistical Test Superiority
Comments If the erenumab 140 mg group for both remaining MPFID secondary endpoints were statistically significant, then the erenumab 70 mg group for the two remaining MPFID secondary endpoints was tested for significance using the Hochberg method with the same alpha level carried over from 140 mg group.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.86
Confidence Interval (2-Sided) 95%
-2.95 to -0.77
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Mean Monthly Average Impact on Everyday Activities Score Measured by MPFID in the Last 3 Months of the Double-blind Treatment Phase
Time Frame 4-week baseline phase and the last 3 months (months 4, 5, and 6) of the 24-week double-blind treatment phase
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was conducted in the efficacy analysis set including participants who received at least 1 dose of study drug and had at least 1 change from baseline measurement in MPFID average impact on everyday activities domain score in the double-blind treatment phase.
Arm/Group Title Placebo Erenumab 70 mg QM Erenumab 140 mg QM
Hide Arm/Group Description:
Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase.
Overall Number of Participants Analyzed 316 312 318
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.30  (0.39) -5.52  (0.39) -5.86  (0.39)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 140 mg QM
Comments Analyzed using a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors (region and prior/current treatment with migraine prophylactic medication), and baseline value as covariates.
Type of Statistical Test Superiority
Comments If the first tier secondary endpoints were statistically significant for both erenumab doses the erenumab 140 mg group for the 2 remaining MPFID secondary endpoints was tested using the Hochberg method at a level of 0.05; If only the erenumab 70 mg group or 140 mg group showed statistical significance for the first tier secondary endpoints then the erenumab 140 group for the 2 remaining MPFID secondary endpoints was tested for significance at a level of either 0.04 or 0.01 respectively.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.57
Confidence Interval (2-Sided) 95%
-3.62 to -1.51
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 70 mg QM
Comments Analyzed using a generalized linear mixed model which includes treatment, visit, treatment by visit interaction, stratification factors (region and prior/current treatment with migraine prophylactic medication), and baseline value as covariates.
Type of Statistical Test Superiority
Comments If the erenumab 140 mg group for both remaining MPFID secondary endpoints were statistically significant, then the erenumab 70 mg group for the two remaining MPFID secondary endpoints was tested for significance using the Hochberg method with the same alpha level carried over from 140 mg group.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.22
Confidence Interval (2-Sided) 95%
-3.28 to -1.16
Estimation Comments [Not Specified]
Time Frame From first dose of study drug up to 16 weeks after the last dose. The double-blind treatment phase was 24 weeks and the open-label treatment phase was 28 weeks.
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title Double-blind Treatment Phase: Placebo Double-blind Treatment Phase: Erenumab 70 mg Double-blind Treatment Phase: Erenumab 140 mg Active Treatment Phase: Erenumab 70 mg Active Treatment Phase: Erenumab 140 mg
Hide Arm/Group Description Participants received placebo once a month (QM) by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase. Participants received erenumab 70 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase. Participants received erenumab 140 mg QM by subcutaneous injection on day 1 and weeks 4, 8, 12, 16, and 20 in the 24-week double-blind treatment phase. Participants received erenumab 70 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase. Participants received erenumab 140 mg subcutaneously at weeks 24, 28, 32, 36, 40, 44, and 48 in the active treatment phase.
All-Cause Mortality
Double-blind Treatment Phase: Placebo Double-blind Treatment Phase: Erenumab 70 mg Double-blind Treatment Phase: Erenumab 140 mg Active Treatment Phase: Erenumab 70 mg Active Treatment Phase: Erenumab 140 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Double-blind Treatment Phase: Placebo Double-blind Treatment Phase: Erenumab 70 mg Double-blind Treatment Phase: Erenumab 140 mg Active Treatment Phase: Erenumab 70 mg Active Treatment Phase: Erenumab 140 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/319 (2.19%)   8/314 (2.55%)   8/319 (2.51%)   14/421 (3.33%)   14/424 (3.30%) 
Cardiac disorders           
Pericarditis  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  1/424 (0.24%) 
Congenital, familial and genetic disorders           
Arrhythmogenic right ventricular dysplasia  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  1/424 (0.24%) 
Eye disorders           
Idiopathic orbital inflammation  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  1/421 (0.24%)  0/424 (0.00%) 
Gastrointestinal disorders           
Dyspepsia  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  1/421 (0.24%)  0/424 (0.00%) 
Gastritis  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  1/421 (0.24%)  0/424 (0.00%) 
Gastrooesophageal reflux disease  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  1/421 (0.24%)  0/424 (0.00%) 
General disorders           
Non-cardiac chest pain  1  1/319 (0.31%)  1/314 (0.32%)  1/319 (0.31%)  0/421 (0.00%)  0/424 (0.00%) 
Hepatobiliary disorders           
Cholelithiasis  1  0/319 (0.00%)  2/314 (0.64%)  0/319 (0.00%)  0/421 (0.00%)  0/424 (0.00%) 
Immune system disorders           
Hypersensitivity  1  1/319 (0.31%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  0/424 (0.00%) 
Infections and infestations           
Appendicitis  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  1/424 (0.24%) 
Clostridium difficile colitis  1  0/319 (0.00%)  0/314 (0.00%)  1/319 (0.31%)  0/421 (0.00%)  0/424 (0.00%) 
Diverticulitis  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  2/424 (0.47%) 
Erysipelas  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  1/424 (0.24%) 
Gastroenteritis viral  1  0/319 (0.00%)  0/314 (0.00%)  1/319 (0.31%)  0/421 (0.00%)  0/424 (0.00%) 
Kidney infection  1  0/319 (0.00%)  0/314 (0.00%)  1/319 (0.31%)  0/421 (0.00%)  0/424 (0.00%) 
Postoperative abscess  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  1/421 (0.24%)  0/424 (0.00%) 
Pyelonephritis  1  0/319 (0.00%)  0/314 (0.00%)  1/319 (0.31%)  0/421 (0.00%)  0/424 (0.00%) 
Pyelonephritis acute  1  0/319 (0.00%)  1/314 (0.32%)  0/319 (0.00%)  0/421 (0.00%)  0/424 (0.00%) 
Sepsis  1  0/319 (0.00%)  0/314 (0.00%)  1/319 (0.31%)  0/421 (0.00%)  0/424 (0.00%) 
Vestibular neuronitis  1  0/319 (0.00%)  0/314 (0.00%)  1/319 (0.31%)  0/421 (0.00%)  0/424 (0.00%) 
Injury, poisoning and procedural complications           
Ankle fracture  1  0/319 (0.00%)  0/314 (0.00%)  1/319 (0.31%)  0/421 (0.00%)  0/424 (0.00%) 
Fall  1  1/319 (0.31%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  0/424 (0.00%) 
Femur fracture  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  1/421 (0.24%)  0/424 (0.00%) 
Intentional overdose  1  1/319 (0.31%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  0/424 (0.00%) 
Post-traumatic neck syndrome  1  0/319 (0.00%)  1/314 (0.32%)  0/319 (0.00%)  0/421 (0.00%)  0/424 (0.00%) 
Radius fracture  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  1/424 (0.24%) 
Subdural haematoma  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  1/424 (0.24%) 
Wound  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  1/421 (0.24%)  0/424 (0.00%) 
Metabolism and nutrition disorders           
Dehydration  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  1/424 (0.24%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  1  1/319 (0.31%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  0/424 (0.00%) 
Back pain  1  0/319 (0.00%)  1/314 (0.32%)  0/319 (0.00%)  0/421 (0.00%)  0/424 (0.00%) 
Osteoarthritis  1  1/319 (0.31%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  0/424 (0.00%) 
Spinal pain  1  0/319 (0.00%)  0/314 (0.00%)  1/319 (0.31%)  0/421 (0.00%)  0/424 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Breast cancer  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  1/424 (0.24%) 
Breast fibroma  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  1/424 (0.24%) 
Prolactin-producing pituitary tumour  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  1/424 (0.24%) 
Uterine leiomyoma  1  0/319 (0.00%)  0/314 (0.00%)  1/319 (0.31%)  0/421 (0.00%)  1/424 (0.24%) 
Nervous system disorders           
Cerebral venous thrombosis  1  0/319 (0.00%)  0/314 (0.00%)  1/319 (0.31%)  0/421 (0.00%)  0/424 (0.00%) 
Idiopathic intracranial hypertension  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  1/421 (0.24%)  0/424 (0.00%) 
Migraine  1  0/319 (0.00%)  1/314 (0.32%)  0/319 (0.00%)  0/421 (0.00%)  0/424 (0.00%) 
Migraine with aura  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  1/421 (0.24%)  0/424 (0.00%) 
Syncope  1  0/319 (0.00%)  0/314 (0.00%)  1/319 (0.31%)  1/421 (0.24%)  0/424 (0.00%) 
Toxic encephalopathy  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  1/421 (0.24%)  0/424 (0.00%) 
Psychiatric disorders           
Depression  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  1/421 (0.24%)  0/424 (0.00%) 
Reproductive system and breast disorders           
Breast cyst  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  1/424 (0.24%) 
Endometriosis  1  1/319 (0.31%)  0/314 (0.00%)  0/319 (0.00%)  0/421 (0.00%)  0/424 (0.00%) 
Ovarian cyst  1  0/319 (0.00%)  1/314 (0.32%)  0/319 (0.00%)  0/421 (0.00%)  0/424 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Nasal septum deviation  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  1/421 (0.24%)  0/424 (0.00%) 
Vascular disorders           
Deep vein thrombosis  1  0/319 (0.00%)  0/314 (0.00%)  0/319 (0.00%)  1/421 (0.24%)  0/424 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 20.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Double-blind Treatment Phase: Placebo Double-blind Treatment Phase: Erenumab 70 mg Double-blind Treatment Phase: Erenumab 140 mg Active Treatment Phase: Erenumab 70 mg Active Treatment Phase: Erenumab 140 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   53/319 (16.61%)   53/314 (16.88%)   54/319 (16.93%)   83/421 (19.71%)   63/424 (14.86%) 
Infections and infestations           
Upper respiratory tract infection  1  19/319 (5.96%)  21/314 (6.69%)  15/319 (4.70%)  25/421 (5.94%)  19/424 (4.48%) 
Viral upper respiratory tract infection  1  34/319 (10.66%)  32/314 (10.19%)  39/319 (12.23%)  58/421 (13.78%)  44/424 (10.38%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 20.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02456740     History of Changes
Other Study ID Numbers: 20120296
2014-004464-38 ( EudraCT Number )
First Submitted: May 14, 2015
First Posted: May 28, 2015
Results First Submitted: June 12, 2018
Results First Posted: July 10, 2018
Last Update Posted: November 29, 2018