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A Study to Assess the Long-term Safety and Efficacy of Erenumab (AMG 334) in Chronic Migraine Prevention.

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ClinicalTrials.gov Identifier: NCT02174861
Recruitment Status : Completed
First Posted : June 26, 2014
Results First Posted : June 19, 2018
Last Update Posted : June 19, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Treatment for Prevention of Chronic Migraine
Intervention Drug: Erenumab
Enrollment 609
Recruitment Details Participants were enrolled at 64 centers across North America and Europe from 30 June 2014 to 4 March 2016. Participants who completed the 12-week double-blind treatment of the parent Study 20120295 (NCT02066415) and met all Study 20130255 eligibility criteria were eligible for enrollment into this study.
Pre-assignment Details Participants at sites in the United States, Sweden, and Germany had the option of enrolling in the Clinical Home Use (CHU) Substudy to assess their ability to self-administer 140 mg erenumab for in-home use. Participants in the substudy were randomized 1:1 to self-administer erenumab using either a prefilled syringe or autoinjector/pen.
Arm/Group Title Erenumab
Hide Arm/Group Description

Participants received erenumab 70 mg once a month (QM) and/or 140 mg QM by subcutaneous injection for up to 52 weeks.

Participants who enrolled prior to amendment 2 received erenumab 70 mg once a month (QM). Participants who had not completed the week 28 visit at the time of amendment 2 had their dose increased to 140 mg QM at their next visit whereas participants who had already completed the week 28 visit remained on erenumab 70 mg QM. Participants who enrolled after amendment 2 received erenumab 140 mg QM for the duration of the study.

Period Title: Overall Study
Started 609
Enrolled in CHU Substudy 53
Completed 451
Not Completed 158
Reason Not Completed
Decision by sponsor             8
Withdrawal by Subject             124
Lost to Follow-up             26
Arm/Group Title Erenumab
Hide Arm/Group Description

Participants received erenumab 70 mg once a month (QM) and/or 140 mg QM by subcutaneous injection for up to 52 weeks.

Participants who enrolled prior to amendment 2 received erenumab 70 mg once a month (QM). Participants who had not completed the week 28 visit at the time of amendment 2 had their dose increased to 140 mg QM at their next visit whereas participants who had already completed the week 28 visit remained on erenumab 70 mg QM. Participants who enrolled after amendment 2 received erenumab 140 mg QM for the duration of the study.

Overall Number of Baseline Participants 609
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 609 participants
42.5  (11.3)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 609 participants
18 - 64 years
608
  99.8%
65 - 74 years
1
   0.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 609 participants
Female
509
  83.6%
Male
100
  16.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 609 participants
Hispanic or Latino
25
   4.1%
Not Hispanic or Latino
584
  95.9%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 609 participants
American Indian or Alaska Native
0
   0.0%
Asian
7
   1.1%
Black or African American
25
   4.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
White
574
  94.3%
Other
3
   0.5%
1.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description Adverse events (AEs) were graded for severity using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where Grade 1 = mild AE, asymptomatic or mild symptoms; Grade 2 = Moderate AE; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences; urgent intervention indicated; Grade 5 = Death related to AE.
Time Frame From first dose of erenumab in extension study 20130255 to the end of the 12-week safety follow-up period (up to 64 weeks).
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who received at least 1 dose of erenumab
Arm/Group Title Erenumab
Hide Arm/Group Description:

Participants received erenumab 70 mg once a month (QM) and/or 140 mg QM by subcutaneous injection for up to 52 weeks.

Participants who enrolled prior to amendment 2 received erenumab 70 mg once a month (QM). Participants who had not completed the week 28 visit at the time of amendment 2 had their dose increased to 140 mg QM at their next visit whereas participants who had already completed the week 28 visit remained on erenumab 70 mg QM. Participants who enrolled after amendment 2 received erenumab 140 mg QM for the duration of the study.

Overall Number of Participants Analyzed 609
Measure Type: Count of Participants
Unit of Measure: Participants
Any adverse event
398
  65.4%
Adverse event grade ≥ 2
302
  49.6%
Adverse event grade ≥ 3
34
   5.6%
Adverse event grade ≥ 4
0
   0.0%
Treatment-related adverse events
114
  18.7%
Serious adverse events
24
   3.9%
AE leading to discontinuation of erenumab
16
   2.6%
Fatal adverse events
0
   0.0%
2.Primary Outcome
Title CHU Substudy: Number of Participants Able to Administer a Full Dose of Erenumab in Home-use
Hide Description At the CHU substudy day 28 and day 56 visits, the site provided erenumab 140 mg to participants to self-administer at home on the following day. Study site staff then called the participants and asked if they administered a full, partial, or no dose of erenumab. A full dose was defined when the entire volume of both prefilled syringes or autoinjector/pens were injected.
Time Frame Day 29 (week 4) and day 57 (week 8) of the substudy
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of erenumab in the CHU substudy.
Arm/Group Title Erenumab 140 mg PFS Erenumab 140 mg AI/Pen
Hide Arm/Group Description:
Participants in the CHU substudy self-administered erenumab 140 mg on days 29 and 57 by subcutaneous injection using a prefilled syringe (PFS).
Participants in the CHU substudy self-administered erenumab 140 mg on days 29 and 57 by subcutaneous injection using a autoinjector/pen (AI/Pen).
Overall Number of Participants Analyzed 27 26
Measure Type: Count of Participants
Unit of Measure: Participants
Week 4
25
  92.6%
26
 100.0%
Week 8
25
  92.6%
25
  96.2%
3.Secondary Outcome
Title Change From Study 20120295 Baseline in Monthly Migraine Days
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 number of migraine days during the 4 weeks prior to each study visit – the number of migraine days during the 4-week baseline phase.

Time Frame 4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40, and 52 visits of Study 20130255
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants who received at least one dose of erenumab and had at least one change from baseline measurement in monthly migraine day in study 20130255. The number of participants analyzed includes participants with available data at each time point.
Arm/Group Title Erenumab
Hide Arm/Group Description:

Participants received erenumab 70 mg once a month (QM) and/or 140 mg QM by subcutaneous injection for up to 52 weeks.

Participants who enrolled prior to amendment 2 received erenumab 70 mg once a month (QM). Participants who had not completed the week 28 visit at the time of amendment 2 had their dose increased to 140 mg QM at their next visit whereas participants who had already completed the week 28 visit remained on erenumab 70 mg QM. Participants who enrolled after amendment 2 received erenumab 140 mg QM for the duration of the study.

Overall Number of Participants Analyzed 605
Mean (Standard Deviation)
Unit of Measure: migraine days / month
Baseline Number Analyzed 605 participants
18.11  (4.53)
Change from baseline at week 4 Number Analyzed 561 participants
-6.72  (6.22)
Change from baseline at week 8 Number Analyzed 574 participants
-7.38  (6.50)
Change from baseline at week 12 Number Analyzed 560 participants
-7.63  (6.49)
Change from baseline at week 24 Number Analyzed 481 participants
-8.36  (6.29)
Change from baseline at week 40 Number Analyzed 430 participants
-8.72  (6.53)
Change from baseline at week 52 Number Analyzed 383 participants
-9.29  (6.64)
4.Secondary Outcome
Title Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Study 20120295 Baseline
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 4 weeks prior to each study visit.

At least a 50% reduction from baseline (of study 20120295) in monthly migraine days was determined if the change in monthly migraine days from the 4-week baseline phase to the 4 weeks prior to each study visit * 100 / baseline monthly migraine days was less than or equal to -50%.

Time Frame 4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40 and 52 visits of Study 20130255
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants who received at least one dose of erenumab and had at least one change from baseline measurement in monthly migraine day in study 20130255. The analysis includes participants with available data at each time point.
Arm/Group Title Erenumab
Hide Arm/Group Description:

Participants received erenumab 70 mg once a month (QM) and/or 140 mg QM by subcutaneous injection for up to 52 weeks.

Participants who enrolled prior to amendment 2 received erenumab 70 mg once a month (QM). Participants who had not completed the week 28 visit at the time of amendment 2 had their dose increased to 140 mg QM at their next visit whereas participants who had already completed the week 28 visit remained on erenumab 70 mg QM. Participants who enrolled after amendment 2 received erenumab 140 mg QM for the duration of the study.

Overall Number of Participants Analyzed 605
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 4 Number Analyzed 561 participants
39.2
(35.3 to 43.3)
Week 8 Number Analyzed 574 participants
45.6
(41.6 to 49.7)
Week 12 Number Analyzed 560 participants
45.7
(41.6 to 49.9)
Week 24 Number Analyzed 481 participants
53.6
(49.2 to 58.0)
Week 40 Number Analyzed 430 participants
55.6
(50.9 to 60.2)
Week 52 Number Analyzed 383 participants
59.0
(54.0 to 63.8)
5.Secondary Outcome
Title Change From Study 20120295 Baseline in Monthly Acute Migraine-Specific Medication Treatment Days
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.
Time Frame 4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40 and 52 visits of Study 20130255
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants who received at least one dose of erenumab and had at least one change from baseline measurement in monthly migraine day in study 20130255. The analysis includes participants with available data at each time point.
Arm/Group Title Erenumab
Hide Arm/Group Description:

Participants received erenumab 70 mg once a month (QM) and/or 140 mg QM by subcutaneous injection for up to 52 weeks.

Participants who enrolled prior to amendment 2 received erenumab 70 mg once a month (QM). Participants who had not completed the week 28 visit at the time of amendment 2 had their dose increased to 140 mg QM at their next visit whereas participants who had already completed the week 28 visit remained on erenumab 70 mg QM. Participants who enrolled after amendment 2 received erenumab 140 mg QM for the duration of the study.

Overall Number of Participants Analyzed 605
Mean (Standard Deviation)
Unit of Measure: acute migraine treatment days / month
Baseline Number Analyzed 605 participants
9.53  (7.26)
Change from baseline at Week 4 Number Analyzed 561 participants
-3.59  (4.62)
Change from baseline at Week 8 Number Analyzed 574 participants
-4.01  (4.96)
Change from baseline at Week 12 Number Analyzed 560 participants
-3.96  (5.03)
Change from baseline at Week 24 Number Analyzed 481 participants
-4.39  (4.99)
Change from baseline at Week 40 Number Analyzed 430 participants
-4.58  (5.00)
Change from baseline at Week 52 Number Analyzed 383 participants
-4.97  (5.33)
6.Secondary Outcome
Title Change From Study 20120295 Baseline in Cumulative Monthly Headache Hours
Hide Description

The cumulative duration of any qualified headache between monthly doses of study drug regardless of acute treatment use.

A qualified headache was defined as follows:

  • a qualified migraine headache (including an aura-only event that is treated with acute migraine-specific medication), or
  • a qualified non-migraine headache, which is a headache that lasted continuously for ≥ 4 hours and was not a qualified migraine headache, or
  • a headache of any duration for which acute headache treatment was administered.
Time Frame 4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40, and 52 visits of Study 20130255
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants who received at least one dose of erenumab and had at least one change from baseline measurement in monthly migraine day in study 20130255. The analysis includes participants with available data at each time point.
Arm/Group Title Erenumab
Hide Arm/Group Description:

Participants received erenumab 70 mg once a month (QM) and/or 140 mg QM by subcutaneous injection for up to 52 weeks.

Participants who enrolled prior to amendment 2 received erenumab 70 mg once a month (QM). Participants who had not completed the week 28 visit at the time of amendment 2 had their dose increased to 140 mg QM at their next visit whereas participants who had already completed the week 28 visit remained on erenumab 70 mg QM. Participants who enrolled after amendment 2 received erenumab 140 mg QM for the duration of the study.

Overall Number of Participants Analyzed 605
Mean (Standard Deviation)
Unit of Measure: hours / month
Baseline Number Analyzed 605 participants
226.84  (125.54)
Change from baseline at week 4 Number Analyzed 561 participants
-79.38  (107.56)
Change from baseline at week 8 Number Analyzed 574 participants
-85.24  (110.24)
Change from Baseline at week 12 Number Analyzed 560 participants
-89.30  (111.47)
Change from Baseline at week 24 Number Analyzed 481 participants
-100.41  (112.30)
Change from Baseline at week 40 Number Analyzed 430 participants
-101.07  (111.77)
Change from Baseline at week 52 Number Analyzed 383 participants
-107.44  (113.60)
7.Secondary Outcome
Title CHU Substudy: Number of Participants With Adverse Events
Hide Description

Adverse events were graded for severity using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Injection site reactions were derived from a Medical Dictionary for Regulatory Activities (MedDRA) query using a list of pre-specified preferred terms.

An adverse device effect (ADE) is any adverse event related to the use of a medical device.

Time Frame From first dose of erenumab in the CHU substudy to 28 days after last dose of erenumab in the CHU substudy; up to 12 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of erenumab in the CHU substudy.
Arm/Group Title Erenumab 140 mg PFS Erenumab 140 mg AI/Pen
Hide Arm/Group Description:
Participants in the CHU substudy self-administered erenumab 140 mg on days 29 and 57 by subcutaneous injection using a prefilled syringe (PFS).
Participants in the CHU substudy self-administered erenumab 140 mg on days 29 and 57 by subcutaneous injection using a autoinjector/pen (AI/Pen).
Overall Number of Participants Analyzed 27 26
Measure Type: Count of Participants
Unit of Measure: Participants
Any adverse event
2
   7.4%
6
  23.1%
Adverse event grade ≥ 2
1
   3.7%
4
  15.4%
Adverse event grade ≥ 3
0
   0.0%
0
   0.0%
Adverse event grade ≥ 4
0
   0.0%
0
   0.0%
Serious adverse events
0
   0.0%
0
   0.0%
AE leading to discontinuation of erenumab
0
   0.0%
0
   0.0%
Fatal adverse events
0
   0.0%
0
   0.0%
Injection site reactions
0
   0.0%
1
   3.8%
Adverse device effects
0
   0.0%
0
   0.0%
Time Frame From first dose of erenumab in extension study 20130255 to the end of the 12-week safety follow-up period (up to 64 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 Erenumab
Hide Arm/Group Description

Participants received erenumab 70 mg once a month (QM) and/or 140 mg QM by subcutaneous injection for up to 52 weeks.

Participants who enrolled prior to amendment 2 received erenumab 70 mg once a month (QM). Participants who had not completed the week 28 visit at the time of amendment 2 had their dose increased to 140 mg QM at their next visit whereas participants who had already completed the week 28 visit remained on erenumab 70 mg QM. Participants who enrolled after amendment 2 received erenumab 140 mg QM for the duration of the study.

All-Cause Mortality
Erenumab
Affected / at Risk (%)
Total   0/609 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Erenumab
Affected / at Risk (%)
Total   24/609 (3.94%) 
Congenital, familial and genetic disorders   
Myocardial bridging  1  1/609 (0.16%) 
Gastrointestinal disorders   
Abdominal pain  1  1/609 (0.16%) 
Oesophagitis  1  1/609 (0.16%) 
Volvulus  1  1/609 (0.16%) 
Hepatobiliary disorders   
Alcoholic liver disease  1  1/609 (0.16%) 
Infections and infestations   
Appendicitis  1  1/609 (0.16%) 
Gastroenteritis viral  1  1/609 (0.16%) 
Pneumonia  1  1/609 (0.16%) 
Injury, poisoning and procedural complications   
Post procedural oedema  1  1/609 (0.16%) 
Musculoskeletal and connective tissue disorders   
Costochondritis  1  1/609 (0.16%) 
Intervertebral disc protrusion  1  3/609 (0.49%) 
Rotator cuff syndrome  1  1/609 (0.16%) 
Nervous system disorders   
Medication overuse headache  1  1/609 (0.16%) 
Migraine  1  4/609 (0.66%) 
Presyncope  1  1/609 (0.16%) 
Radicular syndrome  1  1/609 (0.16%) 
Transient ischaemic attack  1  1/609 (0.16%) 
Vestibular migraine  1  1/609 (0.16%) 
Psychiatric disorders   
Alcoholism  1  1/609 (0.16%) 
Depression  1  2/609 (0.33%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Erenumab
Affected / at Risk (%)
Total   162/609 (26.60%) 
Infections and infestations   
Sinusitis  1  44/609 (7.22%) 
Upper respiratory tract infection  1  45/609 (7.39%) 
Viral upper respiratory tract infection  1  96/609 (15.76%) 
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 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: NCT02174861     History of Changes
Other Study ID Numbers: 20130255
2013-005311-27 ( EudraCT Number )
First Submitted: May 28, 2014
First Posted: June 26, 2014
Results First Submitted: May 24, 2018
Results First Posted: June 19, 2018
Last Update Posted: June 19, 2018