MigrainePhase 2NCT01952574
Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Migraine Prevention
A Phase 2 study testing Erenumab, Erenumab PFS and Erenumab AI/Pen in people with Migraine, run by Amgen at 66 sites in 7 countries.
Trial summary
A study to evaluate the effect of erenumab compared to placebo on the change from baseline in monthly migraine days in participants with episodic migraine. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Migraine
- What is being tested?
- Erenumab, Erenumab PFS and Erenumab AI/Pen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 483 participants
- Where
- 66 sitesin 7 countries
- Study dates
- 6 Aug 2013to 12 Nov 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- History of migraine for more than12 months prior to screening
- Migraine frequency: ≥ 4 and ≤ 14 migraine days per month in each of the 3 months prior to screening and during baseline phase
- Headache frequency: < 15 headache days per month (with > 50% of the headache days being migraine days) in each of the 3 months prior to screening and during baseline phase
- Demonstrated at least 80% compliance with the eDiary during baseline phase
Who cannot join
- Older than 50 years of age at migraine onset
- History of cluster headache or basilar or hemiplegic migraine headache
- Unable to differentiate migraine from other headaches
- No therapeutic response with > 2 of the following eight medication categories for prophylactic treatment of migraine after an adequate therapeutic trial. Medication categories are:
- Category 1: Divalproex sodium, sodium valproate
- Category 2: Topiramate
Show all 13Show fewer
- Category 3: Beta blockers (for example: atenolol, bisoprolol, metoprolol, nadolol, nebivolol, pindolol, propranolol, timolol)
- Category 4: Tricyclic antidepressants (for example: amitriptyline, nortriptyline, protriptyline)
- Category 5: Venlafaxine, desvenlafaxine, duloxetine, milnacipran
- Category 6: Flunarizine, verapamil
- Category 7: Lisinopril, candesartan
- Category 8: Butterbur, feverfew, magnesium (≥ 600 mg/day), riboflavin (≥ 100 mg/day)
- Overuse of acute migraine medications in any month during the 3 months prior to screening or during screening
Trial locations and contacts
66 sites in 7 countries.
66 sites in 7 countries
United States41 sites
Research Site
Ann Arbor, Michigan, 48104
Research Site
Arlington, Texas, 76017
Research Site
Austin, Texas, 78731
Research Site
Bradenton, Florida, 34205
Research Site
Dallas, Texas, 75214
Research Site
Dallas, Texas, 75231
Research Site
Danbury, Connecticut, 06810
Research Site
Decatur, Georgia, 30033
Research Site
Fairfield, Connecticut, 06824
Research Site
Falls Church, Virginia, 22042
Research Site
Greensboro, North Carolina, 27405
Research Site
Houston, Texas, 77074
Research Site
Kalamazoo, Michigan, 49009
Research Site
Lexington, Kentucky, 40513
Research Site
Long Beach, California, 90806
Research Site
Louisville, Kentucky, 40213
Research Site
Melbourne, Florida, 32935
Research Site
Nashville, Tennessee, 37203
Research Site
National City, California, 91950
Research Site
Newport Beach, California, 92663
Research Site
Palm Beach Gardens, Florida, 33410
Research Site
Philadelphia, Pennsylvania, 19107
Research Site
Phoenix, Arizona, 85032
Research Site
Plymouth, Minnesota, 55441
Research Site
Raleigh, North Carolina, 27612
Research Site
Rochester, New York, 14609
Research Site
Salt Lake City, Utah, 84106
Research Site
Salt Lake City, Utah, 84124
Research Site
San Francisco, California, 94109
Research Site
Santa Monica, California, 90404
Research Site
Sherman Oaks, California, 91403
Research Site
Southfield, Michigan, 48034
Research Site
Spring Valley, California, 91978
Research Site
Springfield, Missouri, 65807
Research Site
St Louis, Missouri, 63141
Research Site
Stamford, Connecticut, 06905
Research Site
Virginia Beach, Virginia, 23454
Research Site
Watertown, Massachusetts, 02472
Research Site
West Palm Beach, Florida, 33407
Research Site
Wichita, Kansas, 67207
Research Site
Worcester, Massachusetts, 01605
Germany7 sites
Research Site
Berlin, 10117
Research Site
Berlin, 10409
Research Site
Berlin, 10435
Research Site
Bochum, 44789
Research Site
Essen, 45133
Research Site
Hamburg, 20246
Research Site
Leipzig, 04107
Finland5 sites
Research Site
Helsinki, 00100
Research Site
Mikkeli, 50100
Research Site
Oulu, 90220
Research Site
Tampere, 33100
Research Site
Turku, 20100
Sweden5 sites
Research Site
Falköping, 521 37
Research Site
Lund, 222 22
Research Site
Stockholm, 112 45
Research Site
Stockholm, 114 33
Research Site
Vällingby, 162 68
Norway4 sites
Research Site
Ålesund, 6003
Research Site
Hamar, 2317
Research Site
Sandvika, 1337
Research Site
Stavanger, 4005
Canada2 sites
Research Site
Montreal, Quebec, H2L 4M1
Research Site
Toronto, Ontario, M4S 1Y2
Denmark2 sites
Research Site
Aarhus C, 8000
Research Site
Glostrup Municipality, 2600
About this study
Official title: A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Migraine Prevention
A study to evaluate the effect of erenumab compared to placebo on the change from baseline in monthly migraine days in participants with episodic migraine.
Read the detailed description
The study is composed of an initial screening phase (up to 3 weeks), a 4-week baseline phase, a 12-week double-blind treatment phase (DBTP), an open-label treatment phase (OLTP) for up to 256 weeks, and an 8-week safety follow-up (12 weeks after the last dose of investigational product [IP]).
In the DBTP participants were to be randomized in a 3:2:2:2 ratio to placebo, erenumab 7 mg, erenumab 21 mg, or erenumab 70 mg.
During the open-label treatment phase, participants were to receive erenumab 70 mg QM from week 12 to week 264. After implementation of Protocol Amendment 3 (07 April 2016), participants remaining in the OLTP increased their dose to erenumab 140 mg QM up to week 264. The safety follow-up increased from an 8-week safety follow-up to a 12-week safety follow-up (16 weeks after the last dose of investigational product).
During the OLTP participants enrolled at sites in the United States could enroll in an optional clinical home use (CHU) substudy, per a country-specific protocol amendment dated 20 June 2016. Participants in the CHU substudy were to be randomized 1:1 into 1 of 2 treatment groups: erenumab 140 mg using a prefilled syringe or erenumab 140 mg using an autoinjector/pen. Day 1 of the CHU substudy corresponded with any OLTP study visit up through Week 256, as long as the participant had received at least 2 doses of erenumab 140 mg. During the CHU substudy, participants initially self-administered IP under site supervision on substudy day 1, and then self-administered IP at home on substudy days 29 and 57.
- Conditions
- Migraine
- Being tested
- Erenumab, Placebo, Erenumab PFS, Erenumab AI/Pen
- Keywords
- migraine, headache, prevention, prophylaxis
- Medical subject headings
- Migraine Disorders, Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErenumabDrug
Also called AMG 334, Aimovig™
Administered by study site staff once a month (QM) as a subcutaneous injection
PlaceboDrug
Administered by study site staff once a month (QM) as a subcutaneous injection
Erenumab PFSDrug
Erenumab supplied in a single-use prefilled syringe for self-administration in the CHU substudy
Erenumab AI/PenDrug
Erenumab supplied in a single-use autoinjector/pen for self-administration in the CHU substudy
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase.
In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM. Receives: Drug: Erenumab; Drug: Placebo |
| Erenumab 7 mg QM | Experimental | Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase.
In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM. Receives: Drug: Erenumab |
| Erenumab 21 mg QM | Experimental | Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase.
In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM. Receives: Drug: Erenumab |
| Erenumab 70 mg QM | Experimental | Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase.
In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM. Receives: Drug: Erenumab |
| CHU Substudy: Erenumab 140 mg PFS | Experimental | Participants in the open-label treatment phase in the United States randomized to self-administer 140 mg erenumab via two 70 mg injections using a prefilled syringe (PFS) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8). Receives: Drug: Erenumab PFS |
| CHU Substudy: Erenumab 140 mg AI/Pen | Experimental | Participants in the open-label treatment phase in the United States randomized to self-administer 140 mg erenumab via two 70 mg injections using an autoinjector/pen (AI)/pen) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8). Receives: Drug: Erenumab AI/Pen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Monthly Migraine Days at Week 12
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.
Measured: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
CHU Substudy: Number of Participants Who Self-administered a Full Dose, Partial Dose, or No Dose of Erenumab
To assess participants ability to administer a full dose of erenumab in home-use at day 29 (week 4) and day 57 (week 8), site staff called participants and asked whether the participant administered a full, partial, or no dose of erenumab. A full dose means that the entire volume of both prefilled syringes or autoinjector/pens were injected. Discontinued prior to dosing day indicates participants who had discontinued the investigational product and did not attempt to self-administer on day 29 or 57.
Measured: CHU substudy day 29 (week 4) and day 57 (week 8)
Secondary outcomes (7)
Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Week 12
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%.
Measured: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
Change From Baseline in Monthly Migraine Attacks at Week 12
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.
Measured: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
Number of Participants With Treatment-emergent Adverse Events in the Double-blind Treatment Phase
An adverse event (AE) is any untoward medical occurrence in a clinical trial subject, including worsening of a pre-existing medical condition and laboratory value changes that require treatment or adjustment in current therapy.
AEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03:
- Mild; asymptomatic or mild symptoms
- Moderate; minimal, local or noninvasive intervention indicated; limiting daily activities
- Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling; limiting self-care
- Life-threatening consequences; urgent intervention indicated
- Death related to AE
A serious adverse event is an AE that meets at least 1 of the following criteria:
- fatal
- life threatening
- requires in-patient hospitalization or prolongation of existing hospitalization
- results in persistent or significant disability/incapacity
- congenital anomaly/birth defect
- other medically important serious event
Measured: 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 12 weeks after last dose for participants who did not enter the open-label treatment phase.
Number of Participants With Treatment-emergent Adverse Events in the Open-label Treatment Phase
An adverse event (AE) is any untoward medical occurrence in a clinical trial subject, including worsening of a pre-existing medical condition and laboratory value changes that require treatment or adjustment in current therapy.
AEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03:
- Mild; asymptomatic or mild symptoms
- Moderate; minimal, local or noninvasive intervention indicated; limiting daily activities
- Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling; limiting self-care
- Life-threatening consequences; urgent intervention indicated
- Death related to AE
A serious adverse event is an AE that meets at least 1 of the following criteria:
- fatal
- life threatening
- requires in-patient hospitalization or prolongation of existing hospitalization
- results in persistent or significant disability/incapacity
- congenital anomaly/birth defect
- other medically important serious event
Measured: From first dose in the open-label treatment phase up to 12 weeks (participants receiving 70 mg only) or 16 weeks (participants with dose increased to 140 mg) after the last dose; a maximum of 268 weeks.
CHU Substudy: Number of Participants With Treatment-emergent Adverse Events During the CHU Substudy
AEs were graded using the CTCAE version 4.03:
- Mild; asymptomatic or mild symptoms
- Moderate; minimal, local or noninvasive intervention indicated; limiting daily activities
- Severe or medically significant but not immediately life-threatening; hospitalization indicated; disabling; limiting self-care
- Life-threatening consequences; urgent intervention indicated
- Death related to AE
A serious adverse event is an AE that meets at least 1 of the following criteria:
- fatal
- life threatening
- requires in-patient hospitalization or prolongation of existing hospitalization
- results in persistent or significant disability/incapacity
- congenital anomaly/birth defect
- other medically important serious event An adverse device effect is any AE related to the use of a medical device, including AEs resulting from insufficient or inadequate instructions for use, any malfunction of the device, or use error or from intentional misuse of the device.
Measured: From first dose in the CHU substudy to end of substudy (up to 12 weeks)
Number of Participants Who Developed Anti-erenumab Antibodies During the Double-blind Treatment Phase
Two validated assays were used to detect the presence of anti-erenumab antibodies. First, an electrochemiluminescent bridging immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding erenumab. Second, a cell-based bioassay was used to test positive binding antibody samples for neutralizing activity against erenumab.
Participants who developed anti-erenumab antibodies are participants who were negative or had no result at baseline but positive at any time postbaseline during the DBTP.
If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.
Measured: 12 weeks
Number of Participants Who Developed Anti-erenumab Antibodies During the Open-label Treatment Phase
Two validated assays were used to detect the presence of anti-erenumab antibodies. First, an electrochemiluminescent bridging immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding erenumab. Second, a cell-based bioassay was used to test positive binding antibody samples for neutralizing activity against erenumab.
Participants who developed anti-erenumab antibodies are participants who were negative prior to the first OLTP dose but positive at any time during the OLTP, or participants with no data prior to first dose in OLTP with any post-baseline positive results.
If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies.
Measured: From week 12 up to 12 weeks (participants receiving 70 mg only) or 16 weeks (participants with dose increased to 140 mg) after the last dose; maximum 268 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2013 (estimated)
- Study start6 Aug 2013
- Primary completion25 Sep 2014
- Study completion12 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for MigraineStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In the DBTP participants were randomized to one of four arms. In the optional CHU substudy participants were randomized into one of two treatment groups.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 483 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01952574
- Sponsor's protocol ID
- 20120178
- Other IDs
- 2012-005331-90
- Status last verified
- Oct 2022
- First submitted
- 30 Aug 2013
- Last updated
- 12 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Publications
Sun H, Dodick DW, Silberstein S, Goadsby PJ, Reuter U, Ashina M, Saper J, Cady R, Chon Y, Dietrich J, Lenz R. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Apr;15(4):382-90. doi: 10.1016/S1474-4422(16)00019-3. Epub 2016 Feb 12.
PubMed 26879279Ashina M, Dodick D, Goadsby PJ, Reuter U, Silberstein S, Zhang F, Gage JR, Cheng S, Mikol DD, Lenz RA. Erenumab (AMG 334) in episodic migraine: Interim analysis of an ongoing open-label study. Neurology. 2017 Sep 19;89(12):1237-1243. doi: 10.1212/WNL.0000000000004391. Epub 2017 Aug 23.
PubMed 28835404Ashina M, Goadsby PJ, Reuter U, Silberstein S, Dodick D, Rippon GA, Klatt J, Xue F, Chia V, Zhang F, Cheng S, Mikol DD. Long-term safety and tolerability of erenumab: Three-plus year results from a five-year open-label extension study in episodic migraine. Cephalalgia. 2019 Oct;39(11):1455-1464. doi: 10.1177/0333102419854082. Epub 2019 May 30.
PubMed 31146544Cheng S, Picard H, Zhang F, Eisele O, Mikol DD. Efficacy and safety of erenumab for migraine prevention: an overview. Japanese Journal of Headache. 2019; 45 : 493-505.
Ashina M, Goadsby PJ, Reuter U, Silberstein S, Dodick DW, Xue F, Zhang F, Paiva da Silva Lima G, Cheng S, Mikol DD. Long-term efficacy and safety of erenumab in migraine prevention: Results from a 5-year, open-label treatment phase of a randomized clinical trial. Eur J Neurol. 2021 May;28(5):1716-1725. doi: 10.1111/ene.14715. Epub 2021 Jan 20.
PubMed 33400330Zhou Y, Zhang F, Starcevic Manning M, Hu Z, Hsu CP, Chen PW, Peng C, Loop B, Mytych DT, Paiva da Silva Lima G. Immunogenicity of erenumab: A pooled analysis of six placebo-controlled trials with long-term extensions. Cephalalgia. 2022 Jul;42(8):749-760. doi: 10.1177/03331024221075621. Epub 2022 Mar 10.
PubMed 35272533Ashina M, Kudrow D, Reuter U, Dolezil D, Silberstein S, Tepper SJ, Xue F, Picard H, Zhang F, Wang A, Zhou Y, Hong F, Klatt J, Mikol DD. Long-term tolerability and nonvascular safety of erenumab, a novel calcitonin gene-related peptide receptor antagonist for prevention of migraine: A pooled analysis of four placebo-controlled trials with long-term extensions. Cephalalgia. 2019 Dec;39(14):1798-1808. doi: 10.1177/0333102419888222. Epub 2019 Nov 10.
PubMed 31707815Kudrow D, Pascual J, Winner PK, Dodick DW, Tepper SJ, Reuter U, Hong F, Klatt J, Zhang F, Cheng S, Picard H, Eisele O, Wang J, Latham JN, Mikol DD. Vascular safety of erenumab for migraine prevention. Neurology. 2020 Feb 4;94(5):e497-e510. doi: 10.1212/WNL.0000000000008743. Epub 2019 Dec 18.
PubMed 31852816Sakai F, Takeshima T, Tatsuoka Y, Hirata K, Cheng S, Numachi Y, Peng C, Xue F, Mikol DD. Long-term efficacy and safety during open-label erenumab treatment in Japanese patients with episodic migraine. Headache. 2021 Apr;61(4):653-661. doi: 10.1111/head.14096. Epub 2021 Mar 25.
PubMed 33764538Ashina M, Goadsby PJ, Dodick DW, Tepper SJ, Xue F, Zhang F, Brennan F, Paiva da Silva Lima G. Assessment of Erenumab Safety and Efficacy in Patients With Migraine With and Without Aura: A Secondary Analysis of Randomized Clinical Trials. JAMA Neurol. 2022 Feb 1;79(2):159-168. doi: 10.1001/jamaneurol.2021.4678.
PubMed 34928306
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Migraine Prevention
- ClinicalTrials.gov ID
- NCT01952574
- Acronym / sponsor ID
- 20120178
- Conditions
- Migraine
- Keywords
- migraine, headache, prevention, prophylaxis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 483 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 6 Aug 2013 (actual)
- Primary completion
- 25 Sep 2014 (actual)
- Study completion
- 12 Nov 2019 (actual)
- First posted
- 30 Sep 2013 (estimated)
- Results
- Posted 10 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A study to evaluate the effect of erenumab compared to placebo on the change from baseline in monthly migraine days in participants with episodic migraine.
Detailed description
The study is composed of an initial screening phase (up to 3 weeks), a 4-week baseline phase, a 12-week double-blind treatment phase (DBTP), an open-label treatment phase (OLTP) for up to 256 weeks, and an 8-week safety follow-up (12 weeks after the last dose of investigational product [IP]).
In the DBTP participants were to be randomized in a 3:2:2:2 ratio to placebo, erenumab 7 mg, erenumab 21 mg, or erenumab 70 mg.
During the open-label treatment phase, participants were to receive erenumab 70 mg QM from week 12 to week 264. After implementation of Protocol Amendment 3 (07 April 2016), participants remaining in the OLTP increased their dose to erenumab 140 mg QM up to week 264. The safety follow-up increased from an 8-week safety follow-up to a 12-week safety follow-up (16 weeks after the last dose of investigational product).
During the OLTP participants enrolled at sites in the United States could enroll in an optional clinical home use (CHU) substudy, per a country-specific protocol amendment dated 20 June 2016. Participants in the CHU substudy were to be randomized 1:1 into 1 of 2 treatment groups: erenumab 140 mg using a prefilled syringe or erenumab 140 mg using an autoinjector/pen. Day 1 of the CHU substudy corresponded with any OLTP study visit up through Week 256, as long as the participant had received at least 2 doses of erenumab 140 mg. During the CHU substudy, participants initially self-administered IP under site supervision on substudy day 1, and then self-administered IP at home on substudy days 29 and 57.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 6
- Model description
- In the DBTP participants were randomized to one of four arms. In the optional CHU substudy participants were randomized into one of two treatment groups.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Erenumab, Drug: PlaceboParticipants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM. |
| Erenumab 7 mg QM | Experimental | Drug: ErenumabParticipants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM. |
| Erenumab 21 mg QM | Experimental | Drug: ErenumabParticipants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM. |
| Erenumab 70 mg QM | Experimental | Drug: ErenumabParticipants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM. |
| CHU Substudy: Erenumab 140 mg PFS | Experimental | Drug: Erenumab PFSParticipants in the open-label treatment phase in the United States randomized to self-administer 140 mg erenumab via two 70 mg injections using a prefilled syringe (PFS) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8). |
| CHU Substudy: Erenumab 140 mg AI/Pen | Experimental | Drug: Erenumab AI/PenParticipants in the open-label treatment phase in the United States randomized to self-administer 140 mg erenumab via two 70 mg injections using an autoinjector/pen (AI)/pen) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8). |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- History of migraine for more than12 months prior to screening
- Migraine frequency: ≥ 4 and ≤ 14 migraine days per month in each of the 3 months prior to screening and during baseline phase
- Headache frequency: < 15 headache days per month (with > 50% of the headache days being migraine days) in each of the 3 months prior to screening and during baseline phase
- Demonstrated at least 80% compliance with the eDiary during baseline phase
Key exclusion criteria (13 listed)
- Older than 50 years of age at migraine onset
- History of cluster headache or basilar or hemiplegic migraine headache
- Unable to differentiate migraine from other headaches
- No therapeutic response with > 2 of the following eight medication categories for prophylactic treatment of migraine after an adequate therapeutic trial. Medication categories are:
- Overuse of acute migraine medications in any month during the 3 months prior to screening or during screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ErenumabAlso: AMG 334, Aimovig™Administered by study site staff once a month (QM) as a subcutaneous injection | Drug | Erenumab 21 mg QM, Erenumab 7 mg QM, Erenumab 70 mg QM, Placebo |
| PlaceboAdministered by study site staff once a month (QM) as a subcutaneous injection | Drug | Placebo |
| Erenumab PFSErenumab supplied in a single-use prefilled syringe for self-administration in the CHU substudy | Drug | CHU Substudy: Erenumab 140 mg PFS |
| Erenumab AI/PenErenumab supplied in a single-use autoinjector/pen for self-administration in the CHU substudy | Drug | CHU Substudy: Erenumab 140 mg AI/Pen |
Primary outcome
Change From Baseline in Monthly Migraine Days at Week 12
Time frame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
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.
CHU Substudy: Number of Participants Who Self-administered a Full Dose, Partial Dose, or No Dose of Erenumab
Time frame: CHU substudy day 29 (week 4) and day 57 (week 8)
To assess participants ability to administer a full dose of erenumab in home-use at day 29 (week 4) and day 57 (week 8), site staff called participants and asked whether the participant administered a full, partial, or no dose of erenumab. A full dose means that the entire volume of both prefilled syringes or autoinjector/pens were injected. Discontinued prior to dosing day indicates participants who had discontinued the investigational product and did not attempt to self-administer on day 29 or 57.
7 secondary outcomes
Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Week 12
Time frame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
Change From Baseline in Monthly Migraine Attacks at Week 12
Time frame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
Number of Participants With Treatment-emergent Adverse Events in the Double-blind Treatment Phase
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 12 weeks after last dose for participants who did not enter the open-label treatment phase.
Number of Participants With Treatment-emergent Adverse Events in the Open-label Treatment Phase
Time frame: From first dose in the open-label treatment phase up to 12 weeks (participants receiving 70 mg only) or 16 weeks (participants with dose increased to 140 mg) after the last dose; a maximum of 268 weeks.
CHU Substudy: Number of Participants With Treatment-emergent Adverse Events During the CHU Substudy
Time frame: From first dose in the CHU substudy to end of substudy (up to 12 weeks)
Number of Participants Who Developed Anti-erenumab Antibodies During the Double-blind Treatment Phase
Time frame: 12 weeks
Number of Participants Who Developed Anti-erenumab Antibodies During the Open-label Treatment Phase
Time frame: From week 12 up to 12 weeks (participants receiving 70 mg only) or 16 weeks (participants with dose increased to 140 mg) after the last dose; maximum 268 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26879279Sun H, Dodick DW, Silberstein S, Goadsby PJ, Reuter U, Ashina M, Saper J, Cady R, Chon Y, Dietrich J, Lenz R. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Apr;15(4):382-90. doi: 10.1016/S1474-4422(16)00019-3. Epub 2016 Feb 12.
- Background: PubMed 28835404Ashina M, Dodick D, Goadsby PJ, Reuter U, Silberstein S, Zhang F, Gage JR, Cheng S, Mikol DD, Lenz RA. Erenumab (AMG 334) in episodic migraine: Interim analysis of an ongoing open-label study. Neurology. 2017 Sep 19;89(12):1237-1243. doi: 10.1212/WNL.0000000000004391. Epub 2017 Aug 23.
- Background: PubMed 31146544Ashina M, Goadsby PJ, Reuter U, Silberstein S, Dodick D, Rippon GA, Klatt J, Xue F, Chia V, Zhang F, Cheng S, Mikol DD. Long-term safety and tolerability of erenumab: Three-plus year results from a five-year open-label extension study in episodic migraine. Cephalalgia. 2019 Oct;39(11):1455-1464. doi: 10.1177/0333102419854082. Epub 2019 May 30.
- BackgroundCheng S, Picard H, Zhang F, Eisele O, Mikol DD. Efficacy and safety of erenumab for migraine prevention: an overview. Japanese Journal of Headache. 2019; 45 : 493-505.
- Background: PubMed 33400330Ashina M, Goadsby PJ, Reuter U, Silberstein S, Dodick DW, Xue F, Zhang F, Paiva da Silva Lima G, Cheng S, Mikol DD. Long-term efficacy and safety of erenumab in migraine prevention: Results from a 5-year, open-label treatment phase of a randomized clinical trial. Eur J Neurol. 2021 May;28(5):1716-1725. doi: 10.1111/ene.14715. Epub 2021 Jan 20.
- Background: PubMed 35272533Zhou Y, Zhang F, Starcevic Manning M, Hu Z, Hsu CP, Chen PW, Peng C, Loop B, Mytych DT, Paiva da Silva Lima G. Immunogenicity of erenumab: A pooled analysis of six placebo-controlled trials with long-term extensions. Cephalalgia. 2022 Jul;42(8):749-760. doi: 10.1177/03331024221075621. Epub 2022 Mar 10.
- Background: PubMed 31707815Ashina M, Kudrow D, Reuter U, Dolezil D, Silberstein S, Tepper SJ, Xue F, Picard H, Zhang F, Wang A, Zhou Y, Hong F, Klatt J, Mikol DD. Long-term tolerability and nonvascular safety of erenumab, a novel calcitonin gene-related peptide receptor antagonist for prevention of migraine: A pooled analysis of four placebo-controlled trials with long-term extensions. Cephalalgia. 2019 Dec;39(14):1798-1808. doi: 10.1177/0333102419888222. Epub 2019 Nov 10.
- Background: PubMed 31852816Kudrow D, Pascual J, Winner PK, Dodick DW, Tepper SJ, Reuter U, Hong F, Klatt J, Zhang F, Cheng S, Picard H, Eisele O, Wang J, Latham JN, Mikol DD. Vascular safety of erenumab for migraine prevention. Neurology. 2020 Feb 4;94(5):e497-e510. doi: 10.1212/WNL.0000000000008743. Epub 2019 Dec 18.
- Background: PubMed 33764538Sakai F, Takeshima T, Tatsuoka Y, Hirata K, Cheng S, Numachi Y, Peng C, Xue F, Mikol DD. Long-term efficacy and safety during open-label erenumab treatment in Japanese patients with episodic migraine. Headache. 2021 Apr;61(4):653-661. doi: 10.1111/head.14096. Epub 2021 Mar 25.
- Derived from this study: PubMed 34928306Ashina M, Goadsby PJ, Dodick DW, Tepper SJ, Xue F, Zhang F, Brennan F, Paiva da Silva Lima G. Assessment of Erenumab Safety and Efficacy in Patients With Migraine With and Without Aura: A Secondary Analysis of Randomized Clinical Trials. JAMA Neurol. 2022 Feb 1;79(2):159-168. doi: 10.1001/jamaneurol.2021.4678.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Related trials for Migraine
RecruitingObservational study
Study of the Glymphatic System in Migraine
Migraine
Active, not recruiting
Clinical and Neurophysiological Effects of tDCS to Visual and Motor Cortex in Migraine
Migraine
Active, not recruiting
App-Based Migraine Treatment: The Health enSuite Study
Migraine, Migraine With Aura
Not yet recruiting
A Prospective Study of Rimegepant for Short-term Preventive Treatment of Night-shift-related Migraine in Healthcare Professionals
Migraine Disorders
Recruiting
Marine Lipids Ease Painful TMD
Temporomandibular Disorder (TMD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
66 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Erenumab, Erenumab PFS and Erenumab AI/Pen in people with Migraine, run by Amgen at 66 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 66 sites in United States, Germany, Finland, Sweden, Norway and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Monthly Migraine Days at Week 12 (time frame: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01952574, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2022.