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Trial record 24 of 1110 for:    migraine

A Phase 2 Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Migraine Prevention

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: NCT01952574
Recruitment Status : Active, not recruiting
First Posted : September 30, 2013
Results First Posted : July 10, 2018
Last Update Posted : July 16, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Migraine
Interventions Drug: Erenumab
Drug: Placebo
Enrollment 483
Recruitment Details

This study was conducted at 59 centers in North America (Canada, USA) and Europe (Denmark, Finland, Germany, Norway, Sweden, and Portugal).

Results are reported for the 12-week double-blind treatment phase (data cutoff date 04 November 2014). Three hundred and forty-four participants are ongoing in the open-label extension phase of the study.

Pre-assignment Details Participants were randomized 3:2:2:2 to receive placebo, erenumab 7 mg, erenumab 21 mg, or erenumab 70 mg once a month (QM), respectively. Randomization was stratified by region (North America vs. other).
Arm/Group Title Placebo Erenumab 7 mg QM Erenumab 21 mg QM Erenumab 70 mg QM
Hide Arm/Group Description Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Period Title: Overall Study
Started 160 108 108 107
Received Study Drug 153 108 105 106
Completed [1] 143 105 99 101
Not Completed 17 3 9 6
Reason Not Completed
Withdrawal by Subject             9             3             3             4
Sponsor Decision             6             0             5             2
Lost to Follow-up             2             0             1             0
[1]
Completed double-blind treatment phase
Arm/Group Title Placebo Erenumab 7 mg QM Erenumab 21 mg QM Erenumab 70 mg QM Total
Hide Arm/Group Description Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. Total of all reporting groups
Overall Number of Baseline Participants 160 108 108 107 483
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 160 participants 108 participants 108 participants 107 participants 483 participants
41.4  (10.0) 40.3  (10.9) 39.9  (12.3) 42.6  (9.9) 41.1  (10.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 160 participants 108 participants 108 participants 107 participants 483 participants
Female
132
  82.5%
88
  81.5%
87
  80.6%
82
  76.6%
389
  80.5%
Male
28
  17.5%
20
  18.5%
21
  19.4%
25
  23.4%
94
  19.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 160 participants 108 participants 108 participants 107 participants 483 participants
Hispanic or Latino
11
   6.9%
9
   8.3%
9
   8.3%
1
   0.9%
30
   6.2%
Not Hispanic or Latino
149
  93.1%
99
  91.7%
99
  91.7%
106
  99.1%
453
  93.8%
Unknown or Not Reported
0
   0.0%
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 160 participants 108 participants 108 participants 107 participants 483 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   1.3%
0
   0.0%
1
   0.9%
1
   0.9%
4
   0.8%
Black or African American
13
   8.1%
10
   9.3%
7
   6.5%
2
   1.9%
32
   6.6%
Native Hawaiian or other Pacific Islander
1
   0.6%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
White
142
  88.8%
97
  89.8%
100
  92.6%
103
  96.3%
442
  91.5%
Multiple
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.9%
1
   0.2%
Other
2
   1.3%
1
   0.9%
0
   0.0%
0
   0.0%
3
   0.6%
Region   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 160 participants 108 participants 108 participants 107 participants 483 participants
North America
85
  53.1%
58
  53.7%
58
  53.7%
58
  54.2%
259
  53.6%
Other
75
  46.9%
50
  46.3%
50
  46.3%
49
  45.8%
224
  46.4%
[1]
Measure Description: Region is based on actual data collected at study baseline instead of randomization stratification.
Monthly Migraine Days   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Migraine days/month
Number Analyzed 160 participants 108 participants 108 participants 106 participants 482 participants
8.77  (2.72) 8.62  (2.79) 8.93  (2.88) 8.58  (2.49) 8.73  (2.72)
[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 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 available baseline data
1.Primary Outcome
Title Change From Baseline in Monthly Migraine Days at Week 12
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 as a migraine with or without aura. The change from baseline in monthly migraine days was calculated as the number of migraine days during the last 4 weeks of the 12-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 4 weeks of the 12-week double-blind treatment phase
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of investigational product and had ≥ 4 migraine days during the 4-week baseline phase (efficacy analysis set), and with at least one change from baseline value in monthly migraine days.
Arm/Group Title Placebo Erenumab 7 mg QM Erenumab 21 mg QM Erenumab 70 mg QM
Hide Arm/Group Description:
Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Overall Number of Participants Analyzed 152 107 99 104
Least Squares Mean (Standard Error)
Unit of Measure: migraine days / month
-2.28  (0.31) -2.18  (0.36) -2.39  (0.38) -3.40  (0.37)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 70 mg QM
Comments The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit, the stratification factor region, and baseline value as covariates.
Type of Statistical Test Superiority
Comments To maintain the type I error at ≤ 0.05, the pairwise comparison was tested in a sequential testing procedure in the order of erenumab 70 mg vs placebo, 21 mg vs placebo, and 7 mg vs placebo. The lower dose group was only to be tested when the higher dose group was tested as significant.
Statistical Test of Hypothesis P-Value 0.021
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.12
Confidence Interval (2-Sided) 95%
-2.06 to -0.17
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 21 mg QM
Comments The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit, the stratification factor region, and baseline value as covariates.
Type of Statistical Test Superiority
Comments To maintain the type I error at ≤ 0.05, the pairwise comparison was tested in a sequential testing procedure in the order of erenumab 70 mg vs placebo, 21 mg vs placebo, and 7 mg vs placebo. The lower dose group was only to be tested when the higher dose group was tested as significant.
Statistical Test of Hypothesis P-Value 0.83
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-1.07 to 0.86
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 7 mg QM
Comments The primary analysis utilized a generalized linear mixed model which included treatment, visit, treatment by visit, the stratification factor region, and baseline value as covariates.
Type of Statistical Test Superiority
Comments To maintain the type I error at ≤ 0.05, the pairwise comparison was tested in a sequential testing procedure in the order of erenumab 70 mg vs placebo, 21 mg vs placebo, and 7 mg vs placebo. The lower dose group was only to be tested when the higher dose group was tested as significant.
Statistical Test of Hypothesis P-Value 0.82
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.11
Confidence Interval (2-Sided) 92%
-0.83 to 1.05
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Week 12
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. Monthly migraine days were calculated as the number of migraine days in the 4-week baseline phase and during the last 4 weeks of double-blind treatment. 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 4 weeks of the 12-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 4 weeks of the 12-week double-blind treatment phase
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of investigational product and had ≥ 4 migraine days during the 4-week baseline phase (efficacy analysis set) with available data at week 12.
Arm/Group Title Placebo Erenumab 7 mg QM Erenumab 21 mg QM Erenumab 70 mg QM
Hide Arm/Group Description:
Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Overall Number of Participants Analyzed 144 104 93 99
Measure Type: Number
Unit of Measure: percentage of participants
29.9 28.8 34.4 46.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 70 mg QM
Comments The generalized linear mixed model includes data for all participants in the efficacy analysis set with at least one percent change from baseline value in monthly migraine days (152 participants in the placebo group and 104 in the erenumab 70 mg group)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method Generalised Linear Mixed Model
Comments Generalized linear mixed model including treatment, visit, treatment by visit, stratification factor region, and baseline value as covariates.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.00
Confidence Interval (2-Sided) 95%
1.17 to 3.42
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 21 mg QM
Comments The generalized linear mixed model includes data for all participants in the efficacy analysis set with at least one change from baseline value in monthly migraine days (152 participants in the placebo group and 99 in the erenumab 21 mg group)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.44
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments Generalized linear mixed model including treatment, visit, treatment by visit, stratification factor region, and baseline value as covariates.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
0.71 to 2.18
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 7 mg QM
Comments The generalized linear mixed model includes data for all participants in the efficacy analysis set with at least one change from baseline value in monthly migraine days (152 participants in the placebo group and 107 in the erenumab 7 mg group)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.80
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments Generalized linear mixed model including treatment, visit, treatment by visit, stratification factor region, and baseline value as covariates.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.53 to 1.63
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Monthly Migraine Attacks at Week 12
Hide Description

A migraine attack is an episode of any qualified migraine headache or migraine specific medication intakes for aura only. A migraine attack that was interrupted by sleep or that temporarily remits and then recurs within 48 hours or an attack treated successfully with medication but that relapses within 48 hours was considered to be one attack.

The change from baseline in monthly migraine attacks was calculated as the number of migraine attacks during the last 4 weeks of the 12-week double-blind treatment phase – the number of migraine attacks during the 4-week baseline phase.

Time Frame 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of investigational product and had ≥ 4 migraine days during the 4-week baseline phase (efficacy analysis set), and with at least one change from baseline value in monthly migraine attacks.
Arm/Group Title Placebo Erenumab 7 mg QM Erenumab 21 mg QM Erenumab 70 mg QM
Hide Arm/Group Description:
Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
Overall Number of Participants Analyzed 152 107 99 104
Least Squares Mean (Standard Error)
Unit of Measure: migraine attacks/month
-1.44  (0.17) -1.07  (0.20) -1.42  (0.21) -1.84  (0.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 70 mg QM
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments Generalized linear mixed model including treatment, visit, treatment by visit, the stratification factor region, and baseline value as covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-0.92 to 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 21 mg QM
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.95
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments Generalized linear mixed model including treatment, visit, treatment by visit, the stratification factor region, and baseline value as covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.51 to 0.54
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Erenumab 7 mg QM
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments [Not Specified]
Method Generalized Linear Mixed Model
Comments Generalized linear mixed model including treatment, visit, treatment by visit, the stratification factor region, and baseline value as covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.37
Confidence Interval (2-Sided) 95%
-0.14 to 0.87
Estimation Comments [Not Specified]
Time Frame From first dose of study drug in the double-blind treatment phase until the first dose of study drug in the open-label treatment phase (12 weeks) or up to 84 days after last dose for participants who did not enter the open-label treatment phase.
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title Placebo Erenumab 7 mg QM Erenumab 21 mg QM Erenumab 70 mg QM
Hide Arm/Group Description Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase. Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection in the double-blind treatment phase.
All-Cause Mortality
Placebo Erenumab 7 mg QM Erenumab 21 mg QM Erenumab 70 mg QM
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Erenumab 7 mg QM Erenumab 21 mg QM Erenumab 70 mg QM
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/153 (0.00%)   1/108 (0.93%)   0/105 (0.00%)   1/106 (0.94%) 
Ear and labyrinth disorders         
Vertigo  1  0/153 (0.00%)  0/108 (0.00%)  0/105 (0.00%)  1/106 (0.94%) 
Nervous system disorders         
Migraine  1  0/153 (0.00%)  0/108 (0.00%)  0/105 (0.00%)  1/106 (0.94%) 
Reproductive system and breast disorders         
Ovarian cyst ruptured  1  0/153 (0.00%)  1/108 (0.93%)  0/105 (0.00%)  0/106 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Erenumab 7 mg QM Erenumab 21 mg QM Erenumab 70 mg QM
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/153 (7.84%)   10/108 (9.26%)   5/105 (4.76%)   6/106 (5.66%) 
Infections and infestations         
Nasopharyngitis  1  12/153 (7.84%)  10/108 (9.26%)  5/105 (4.76%)  6/106 (5.66%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
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
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01952574     History of Changes
Other Study ID Numbers: 20120178
2012-005331-90 ( EudraCT Number )
First Submitted: August 30, 2013
First Posted: September 30, 2013
Results First Submitted: June 11, 2018
Results First Posted: July 10, 2018
Last Update Posted: July 16, 2019