Clinical Trial Results:
An Open-label Extension (OLE) Study to Assess the Long-term Safety and Efficacy of AMG 334
|
Summary
|
|
EudraCT number |
2013-005311-27 |
Trial protocol |
SE DE DK NO PL CZ FI GB |
Global end of trial date |
26 May 2017
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
09 Jun 2018
|
First version publication date |
09 Jun 2018
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
20130255
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02174861 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Amgen Inc.
|
||
Sponsor organisation address |
One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
|
||
Public contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
|
||
Scientific contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
09 Aug 2017
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
26 May 2017
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The primary objective was to characterize the safety and tolerability of long-term administration of erenumab.
|
||
Protection of trial subjects |
This study was conducted in accordance with International Council for Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines, the GCPs applicable to all regions where the study was conducted and in accordance with the ethical principles set forth in the Declaration of Helsinki.
The study protocol and all amendments, the informed consent form, and any accompanying materials provided to subjects were reviewed and approved by an independent Ethics Committee (IEC) or Institutional Review Board (IRB), as appropriate, at each center/country.
The investigator or his/her designee informed the subject of all aspects pertaining to the subject’s participation in the study before any screening procedures were performed.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Jun 2014
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Canada: 10
|
||
Country: Number of subjects enrolled |
United States: 276
|
||
Country: Number of subjects enrolled |
Czech Republic: 52
|
||
Country: Number of subjects enrolled |
Denmark: 24
|
||
Country: Number of subjects enrolled |
Finland: 35
|
||
Country: Number of subjects enrolled |
Germany: 69
|
||
Country: Number of subjects enrolled |
Norway: 31
|
||
Country: Number of subjects enrolled |
Poland: 31
|
||
Country: Number of subjects enrolled |
Sweden: 63
|
||
Country: Number of subjects enrolled |
United Kingdom: 18
|
||
Worldwide total number of subjects |
609
|
||
EEA total number of subjects |
323
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
608
|
||
From 65 to 84 years |
1
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||||||
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 (2013-001707-36) and met all Study 20130255 eligibility criteria were eligible for enrollment into this study. | ||||||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||||||
Screening 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. | ||||||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||||||
|
Arm title
|
Erenumab | ||||||||||||||||||||||||
Arm 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. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Erenumab
|
||||||||||||||||||||||||
Investigational medicinal product code |
AMG 334
|
||||||||||||||||||||||||
Other name |
Aimovig™
|
||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||||||
Dosage and administration details |
Administered by subcutaneous injection once a month
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Data represent the number of subjects who enrolled prior to implementation of protocol amendment 2 and received erenumab 70 mg QM for the entire study. [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Data represent the number of subjects who enrolled prior to implementation of protocol amendment 2 and initially received erenumab 70 mg QM and whose dose was increased to 140 mg QM after protocol amendment 2. [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Data represent the number of subjects who enrolled after implementation of protocol amendment 2 and received erenumab 140 mg QM for the duration of the study. [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Data represent the number of subjects who enrolled in the CHU substudy |
|||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall Study
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Erenumab
|
||
Reporting 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. | ||
Subject analysis set title |
Erenumab 140 mg PFS
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants in the CHU substudy self-administered erenumab 140 mg on days 29 and 57 by subcutaneous injection using a prefilled syringe (PFS).
|
||
Subject analysis set title |
Erenumab 140 mg AI/Pen
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants in the CHU substudy self-administered erenumab 140 mg on days 29 and 57 by subcutaneous injection using a autoinjector/pen (AI/Pen).
|
||
|
|||||||||||||||||||||||
End point title |
Number of Participants with Adverse Events [1] | ||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||
End point timeframe |
From first dose of erenumab in extension study 20130255 to the end of the 12-week safety follow-up period (up to 64 weeks).
|
||||||||||||||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The clinical hypothesis was that long-term exposure of erenumab would be safe and well tolerated in subjects with chronic migraine. No formal hypothesis was tested. This was a single-arm estimation study. |
|||||||||||||||||||||||
|
|||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||
|
||||||||||||||||
End point title |
CHU Substudy: Number of Participants Able to Administer a Full Dose of Erenumab in Home-use [2] | |||||||||||||||
End point 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.
|
|||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
Day 29 (week 4) and day 57 (week 8) of the substudy
|
|||||||||||||||
| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: In the CHU substudy it was hypothesized that users were able to administer a full dose of erenumab comparably using either the prefilled syringe or autoinjector/pen. No formal hypotheses were tested. |
||||||||||||||||
|
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
|||||||||||||||||||||||
End point title |
Change from Study 20120295 Baseline in Monthly Migraine Days | ||||||||||||||||||||||
End point 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.
The number of participants analyzed includes 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 and with available data at each time point.
|
||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||
End point timeframe |
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
|
||||||||||||||||||||||
|
|||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Percentage of Participants with at Least a 50% Reduction in Monthly Migraine Days From Study 20120295 Baseline | ||||||||||||||||||||
End point 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%.
The number of participants analyzed includes 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 and with available data at each time point.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
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
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||||
End point title |
Change From Study 20120295 Baseline in Monthly Acute Migraine-Specific Medication Treatment Days | ||||||||||||||||||||||
End point 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 number of participants analyzed includes 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 and with available data at each time point.
|
||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||
End point timeframe |
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
|
||||||||||||||||||||||
|
|||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||
|
|||||||||||||||||||||||
End point title |
Change From Study 20120295 Baseline in Cumulative Monthly Headache Hours | ||||||||||||||||||||||
End point 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.
The number of participants analyzed includes 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 and with available data at each time point.
|
||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||
End point timeframe |
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
|
||||||||||||||||||||||
|
|||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
End point title |
CHU Substudy: Number of Participants with Adverse Events | ||||||||||||||||||||||||||||||||||||
End point 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.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
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.
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From first dose of erenumab in extension study 20130255 to the end of the 12-week safety follow-up period (up to 64 weeks).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Erenumab
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received erenumab 70 mg once a month (QM) and/or 140 mg QM by subcutaneous injection for up to 52 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
25 Jan 2015 |
- updated to extend treatment phase by 3 months to align with 20120295 parent study
- added novel PRO substudy for English-speaking subjects in US only
- added Event Adjudication Committee to cover data from this study
- refined some eligibility criteria and clarified some protocol text |
||
14 Oct 2015 |
- primary objective and secondary objective of CHU substudy were added; 2 secondary and 1 exploratory objectives were added to the main study; 1 secondary objective was deleted; and 1 exploratory objective was modified
- Study Rationale section was updated to include results from
AMG 334 2012078 global phase 2 study
- AMG 334 was increased to 140 mg to provide additional 6-month and one-year safety data at this dose
- sample size was increased from 490 subjects to 651 subjects to align with increase in parent study
- expansion of novel PRO substudy to all subjects, not just
English-speaking subjects
- added clarification to text of CHU substudy
- expanded description of C-SSRS
- clarified protocol text |
||
31 Mar 2016 |
- clarified language regarding length of time surrounding excluded treatments
- aligned current protocol template language (Sections 9 and 12)
- updated pregnancy and lactation notification worksheets
- clarifications made to product complaints section
- review of adverse events and serious adverse events added to Open-label treatment phase
- serious adverse events collection added for CHU substudy
- correct typographical, grammatical, and formatting errors throughout the protocol |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
