Migraine DisordersPhase 3PROMISE 2NCT02974153

Evaluation of ALD403 (Eptinezumab) in the Prevention of Chronic Migraine

A Phase 3 study testing ALD403 (Eptinezumab) in people with Migraine Disorders, run by Alder Biopharmaceuticals, Inc. at 144 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this study is to assess the efficacy and safety of ALD403 in the prevention of migraine headache in chronic migraineurs. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Migraine Disorders
What is being tested?: ALD403 (Eptinezumab)
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 1,121 participants
Where: 144 sitesin 13 countries
Study dates: Nov 2016to Apr 2018
Phase: Phase 3
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Males and females between 18 and 65 years of age, inclusive, who were diagnosed with migraines at ≤ 50 years of age, and have a history of chronic migraine for ≥ 12 months before screening.
During the 28 day screening period, subjects must adequately complete the headache eDiary and must have headaches occurring on ≥ 15 to ≤ 26 days of which at least 8 must be migraine days.
Headache eDiary was completed on at least 24 of the 28 days prior to randomization.

Who cannot join

Confounding and clinically significant pain syndromes (e.g. fibromyalgia, chronic low back pain, complex regional pain syndrome).
Psychiatric conditions that are uncontrolled and/or untreated, including conditions that are not controlled for a minimum of 6 months prior to screening. Patients with a lifetime history of psychosis, mania, or dementia are excluded.
Any use of botulinum toxin for migraine or for any other medical/cosmetic reasons requiring injections within 4 months prior to screening and during the screening period.
History or diagnosis of complicated migraine (ICHD-III beta version, 20134), chronic tension-type headache, hypnic headache, cluster headache, hemicrania continua, new daily persistent headache, or sporadic and familial hemiplegic migraine.
Receipt of any monoclonal antibody treatment (within or outside a clinical trial) within 6 months before screening.
Previously dosed with ALD403 or any monoclonal antibody targeting the CGRP pathway.

Trial locations and contacts

144 sites in 13 countries.

Country

City, postcode or hospital

144 sites in 13 countries

United States74 sites

Research Site
Albuquerque, New Mexico, 87102
Research Site
Amherst, New York, 14226
Research Site
Anderson, Indiana, 46011
Research Site
Ann Arbor, Michigan, 48104
Research Site
Atlanta, Georgia, 30328
Research Site
Atlanta, Georgia, 30342
Research Site
Bellevue, Washington, 98007
Research Site
Birmingham, Alabama, 35235
Research Site
Boston, Massachusetts, 02135
Research Site
Brooklyn, New York, 11229
Research Site
Canton, Ohio, 44718
Research Site
Carlsbad, California, 92011
Research Site
Champaign, Illinois, 61820
Research Site
Chattanooga, Tennessee, 37404
Research Site
Chattanooga, Tennessee, 37421
Research Site
Chicago, Illinois, 60607
Research Site
Chicago, Illinois, 60642
Research Site
City of Saint Peters, Missouri, 63303
Research Site
Colorado Springs, Colorado, 80918
Research Site
Dallas, Texas, 75214
Research Site
Dayton, Ohio, 45432
Research Site
Decatur, Georgia, 30030
Research Site
Des Moines, Iowa, 50309
Research Site
Durham, North Carolina, 27705
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Flowood, Mississippi, 39232
Research Site
High Point, North Carolina, 27262
Research Site
Houston, Texas, 77058
Research Site
Houston, Texas, 77081
Research Site
Jacksonville, Florida, 32256
Research Site
Las Vegas, Nevada, 89113
Research Site
Lebanon, New Hampshire, 03756
Research Site
Little Rock, Arkansas, 72211
Research Site
Marrero, Louisiana, 70072
Research Site
Memphis, Tennessee, 38119
Research Site
Miami, Florida, 33155
Research Site
Minneapolis, Minnesota, 55402
Research Site
Mt. Pleasant, South Carolina, 29464
Research Site
Nashville, Tennessee, 37203
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New London, Connecticut, 06320
Research Site
New York, New York, 10016
Research Site
New York, New York, 10019
Research Site
North Attleboro, Massachusetts, 02740
Research Site
North Richland Hills, Texas, 76180
Research Site
Oceanside, California, 92056
Research Site
Oklahoma City, Oklahoma, 73116
Research Site
Orange, California, 92868
Research Site
Orlando, Florida, 32806
Research Site
Overland Park, Kansas, 66212
Research Site
Oxnard, California, 93030
Research Site
Palo Alto, California, 94304
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Phoenix, Arizona, 85032
Research Site
Plainview, New York, 11803
Research Site
Prairie Village, Kansas, 66208
Research Site
Princeton, New Jersey, 08540
Research Site
Redlands, California, 92374
Research Site
Richmond, Virginia, 23294
Research Site
Rochester, New York, 14609
Research Site
Salt Lake City, Utah, 84109
Research Site
Salt Lake City, Utah, 84123
Research Site
San Antonio, Texas, 78258
Research Site
San Diego, California, 92108
Research Site
Santa Monica, California, 90404
Research Site
Scottdale, Pennsylvania, 15683
Research Site
Smithfield, Pennsylvania, 15478
Research Site
Spokane, Washington, 99202
Research Site
Springfield, Missouri, 65810
Research Site
St Louis, Missouri, 63141
Research Site
Tampa, Florida, 33606
Research Site
Torrance, California, 90502
Research Site
Waldorf, Maryland, 20603
Research Site
Watertown, Massachusetts, 02472
Research Site
West Palm Beach, Florida, 33407
Research Site
Wichita, Kansas, 67207
Research Site
Winter Haven, Florida, 33880

Other trials in United States

Spain14 sites

Research Site
Alicante, 03010
Research Site
Barcelona, 08035
Research Site
Guadalajara, 19002
Research Site
Lleida, 25198
Research Site
Madrid, 28046
Research Site
Madrid, 28050
Research Site
Madrid, 28222
Research Site
Madrid, 28223
Research Site
Navarrés, 31008
Research Site
Santander, 39008
Research Site
Seville, 41013
Research Site
Terrassa, 08221
Research Site
Valencia, 46026
Research Site
Valladolid, 47005

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Russia10 sites

Research Site
Kazan', 420064
Research Site
Krasnoyarsk, 660037
Research Site
Moscow, 121467
Research Site
Novosibirsk, 630051
Research Site
Novosibirsk, 630054
Research Site
Saint Petersburg, 191144
Research Site
Saint Petersburg, 194044
Research Site
Saint Petersburg, 194223
Research Site
Yaroslavl, 150030
Research Site
Yekaterinburg, 620102

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Ukraine9 sites

Research Site
Dnipro, 49045
Research Site
Dnipropetrovsk, 49027
Research Site
Ivano-Frankivsk, 76008
Research Site
Kharkiv, 61068
Research Site
Kharkiv, 61103
Research Site
Lviv, 79010
Research Site
Odesa, 65014
Research Site
Vinnytsia, 21005
Research Site
Zaporizhzhya, 69065

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Italy6 sites

Research Site
Ancona, 60020
Research Site
Milan, 20132
Research Site
Milan, 20133
Research Site
Naples, 80131
Research Site
Pavia, 27100
Research Site
Roma, 00163

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United Kingdom6 sites

Research Site
Glasgow, G51 4TF
Research Site
Inverness, IV2 3UJ
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London, SE5 9PL
Research Site
Newcastle, NE1 4LP
Research Site
Salford, M8 8HD
Research Site
Stoke-on-Trent, ST4 7LN

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Germany5 sites

Research Site
Berlin, 10117
Research Site
Erlangen, 91054
Research Site
Hamburg, 20246
Research Site
Nordheim, 45122
Research Site
Unterhaching, 82008

Other trials in Germany

Czechia4 sites

Research Site
Brno, 61500
Research Site
Choceň, 565 01
Research Site
Prague, 100 34
Research Site
Prague, 18200

Other trials in Czechia

Georgia4 sites

Research Site
Tbilisi, 0112
Research Site
Tbilisi, 0160
Research Site
Tbilisi, 0179
Research Site
Tbilisi, 0186

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Hungary4 sites

Research Site
Budapest, 1033
Research Site
Budapest, 1083
Research Site
Budapest, 1145
Research Site
Pécs, 7623

Other trials in Hungary

Slovakia4 sites

Research Site
Banská Bystrica, 97404
Research Site
Dolný Kubín, 026 01
Research Site
Dubnica nad Váhom, 01841
Research Site
Krompachy, 053 42

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Belgium2 sites

Research Site
Brussels, 1090
Research Site
Liège, 4000

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Denmark2 sites

Research Site
Glostrup Municipality, 2600
Research Site
Viborg, 8800

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About this study

Official title: A Parallel Group, Double-Blind, Randomized, Placebo Controlled Phase 3 Trial to Evaluate the Efficacy and Safety of ALD403 Administered Intravenously in Patients With Chronic Migraine

The purpose of this study is to assess the efficacy and safety of ALD403 in the prevention of migraine headache in chronic migraineurs.

Conditions: Migraine Disorders
Being tested: ALD403 (Eptinezumab), Placebo
Medical subject headings: Migraine Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ALD403 (Eptinezumab)Biological
Also called Eptinezumab-jjmr, Vyepti
PlaceboBiological

Study groups in NCT02974153
Study group	Role	What they receive
ALD403 (Eptinezumab) Dose Level 1	Experimental	ALD403 (Eptinezumab) Dose Level 1 (IV) Receives: Biological: ALD403 (Eptinezumab)
ALD403 (Eptinezumab) Dose Level 2	Experimental	ALD403 (Eptinezumab) Dose Level 2 (IV) Receives: Biological: ALD403 (Eptinezumab)
Placebo	Placebo comparator	Placebo (IV) Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Monthly Migraine Days
Monthly migraine days are summarized in 28-day intervals, and averaged across Weeks 1-12
Measured: Week 1-12

Secondary outcomes (26)

75% Migraine Responder Rate
Participants with an average reduction in migraine days of at least 75% over Weeks 1 to 12, as compared with baseline.
Measured: Week 1-12
75% Migraine Responder Rate - 4 Week
Participants with an average reduction in migraine days of at least 75% over Weeks 1 to 4, as compared with baseline.
Measured: Week 1-4
50% Migraine Responder Rate
Participants with an average reduction in migraine days of at least 50% over Weeks 1 to 12, as compared with baseline.
Measured: Week 1-12
Percentage of Participants With a Migraine on the Day After Dosing
The percentage of participants with a migraine on the day after dosing, where Day 0 is treatment Day and Day 1 is the day after dosing.
Measured: Day 1
Change in Monthly Acute Medication Days
An acute medication migraine day was a day with any triptan or ergotamine use as recorded in the eDiary.
Measured: Week 1-12
Change From Baseline of Headache Impact Test (HIT-6) Score
The HIT-6 measures the impact of headache on the participant's functional health and well-being in 6 domains: pain; role functioning (ability to carry out usual activities); social functioning; energy or fatigue; cognition; and emotional distress assessed over the prior 12-week period. The total possible scores range from 36 (no impact) to 78 (worst impact).
Measured: Baseline to Week 12
Change in Migraine Prevalence From Baseline to Week 4
The avarage change in percentage of participants with a migraine on any given day during baseline and the equivalent avarage rate over Weeks 1-4.
Measured: Baseline to Week 4
75% Headache Responder Rate
Participants with an average reduction in headache days of at least 75% over Weeks 1 to 12, as compared with baseline.
Measured: Week 1-12
50% Headache Responder Rate
Participants with an average reduction in headache days of at least 50% over Weeks 1 to 12, as compared with baseline.
Measured: Week 1-12
100% Migraine Responder Rate
For each 4-week period the 100% response is determined, and the result for a participant is the average rate across Weeks 1-12. If a participant has one 4-week period out of 3 with 100% response, they are included as 33%.
Measured: Week 1-12
100% Headache Responder Rate
For each 4-week period the 100% response is determined, and the result for a participant is the average rate across Weeks 1-12. If a participant has one 4-week period out of 3 with 100% response, they are included as 33%.
Measured: Week 1-12
Change From Baseline in Monthly Migraine Days (Weeks 13-24)
Monthly migraine days are summarized in 28-day intervals, and averaged across Weeks 13-24.
Measured: Week 13-24
Change From Baseline in Monthly Headache Days (Weeks 1-12)
Monthly headache days are summarized in 28-day intervals, and averaged across Weeks 1-12.
Measured: Week 1-12
Time to First Migraine After Dosing
The time to first migraine after dosing based upon the migraine data entered into the eDiary
Measured: 32 weeks
Change From Baseline to Week 12 in Percentage of Migraines With Use of Acute Medication
The percentage of migraines with acute medication usage. Participants with no migraine will be included with a rate of zero.
Measured: Week 1-12
Change From Baseline to Week 12 in Percentage of Headaches With Use of Acute Medication
The percentage of headaches with acute medication usage. Participants with no headaches will be included with a rate of zero.
Measured: Week 1-12
Percent Change in Frequency of Migraine Days - Week 1-12
The percent change in frequency of migraine days from Weeks 1-12 was calculated as the number of migraine days within 4-week intervals that were then averaged up to Week 12. The difference of this estimate from baseline was calculated as the change from baseline in the frequency of migraine days over Weeks 1-12.
Measured: Week 1-12
Percent Change in Frequency of Headache Days - Week 1-12
The percent change in frequency of headache days from Weeks 1-12 was calculated as the number of headache days within 4-week intervals that were then averaged up to Week 12. The difference of this estimate from baseline was calculated as the change from baseline in the frequency of headache days over Weeks 1-12.
Measured: Week 1-12
Change From Baseline in Percentage of Severe Migraines
The change from baseline in percentage of migraines that are classified as severe over Weeks 1-12.
Measured: Week 1-12
Change From Baseline in Percentage of Severe Headache
The change from baseline in percentage of headaches that are classified as severe over Weeks 1-12.
Measured: Week 1-12
Change From Baseline in Monthly Migraine Hours, Weeks 1-12
Migraine hours are the sum of migraines within 4 week intervals, and the average 4 week duration within 12 weeks.
Measured: Week 1-12
Change From Baseline in Monthly Headache Hours, Weeks 1-12
Headache hours are the sum of the duration of headaches within 4 week intervals, and the average 4 week duration within 12 week intervals.
Measured: Week 1-12
Duration of Migraine-Free Intervals
The number of participants with migraine-free intervals starting within the first 2 weeks of treatment. The longest migraine free interval for each participant is recorded.
Measured: 32 weeks
Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores
The SF-36 is a health survey containing 36 questions consisting of eight scaled scores to measure quality of life over the past 4 weeks. All scales are on a range of 0 to 100, with 0 being the worst and 100 being the best. Scales are reported separately. Increases from baseline indicate improvement.
Measured: Baseline to Week 12
Patient Global Impression of Change (PGIC) at Week 12
The PGIC includes a single question concerning the participant's impression of the change in their disease status since the start of the study. Seven responses are possible: Very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse.
Measured: Week 12
Health Related Quality of Life (EQ-5D-5L) at Week 12
The EQ-5D-5L is a descriptive system of health-related quality of life states consisting of 5 dimensions/questions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which can take one of five responses. The responses record five levels of severity (no problems/slight problems/moderate problems/severe problems/extreme problems) within a particular EQ-5D dimension.
Measured: Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2016Apr 2018

First posted28 Nov 2016 (estimated)
Study startNov 2016
Primary completionNov 2017
Study completionApr 2018

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 (14)Papers the sponsor has linked to this study.
Other trials for Migraine DisordersStudies of the same condition, open and under way.
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 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 1,121 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02974153
Sponsor's protocol ID: ALD403-CLIN-011
Acronym: PROMISE 2
Status last verified: May 2020
First submitted: 23 Nov 2016
Last updated: 9 Jun 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Tepper SJ, Diamond ML, Hirman J, Asher D, Fiore D, Cady R. Eptinezumab treatment was associated with longer interictal headache/migraine periods which corresponded to greater improvements in patient-reported quality of life measures. J Neurol. 2024 Dec 12;272(1):4. doi: 10.1007/s00415-024-12809-z.
PubMed 39666143
Kaniecki RG, Friedman DI, Asher D, Hirman J, Cady R. Improving to Four or Fewer Monthly Headache Days Per Month Provides a Clinically Meaningful Therapeutic Target for Patients with Chronic Migraine. Pain Ther. 2023 Oct;12(5):1179-1194. doi: 10.1007/s40122-023-00525-x. Epub 2023 Jun 28.
PubMed 37378754
Pozo-Rosich P, Dodick DW, Ettrup A, Hirman J, Cady R. Shift in diagnostic classification of migraine after initiation of preventive treatment with eptinezumab: post hoc analysis of the PROMISE studies. BMC Neurol. 2022 Oct 25;22(1):394. doi: 10.1186/s12883-022-02914-9.
PubMed 36284281
Cowan RP, Marmura MJ, Diener HC, Starling AJ, Schim J, Hirman J, Brevig T, Cady R. Quantity changes in acute headache medication use among patients with chronic migraine treated with eptinezumab: subanalysis of the PROMISE-2 study. J Headache Pain. 2022 Sep 6;23(1):115. doi: 10.1186/s10194-022-01482-0.
PubMed 36068494
Apelian R, Boyle L, Hirman J, Asher D. Measuring dose-related efficacy of eptinezumab for migraine prevention: post hoc analysis of PROMISE-1 and PROMISE-2. J Headache Pain. 2022 Apr 18;23(1):48. doi: 10.1186/s10194-022-01418-8.
PubMed 35436857
McAllister P, Kudrow D, Cady R, Hirman J, Ettrup A. Reduction in migraine-associated burden after eptinezumab treatment in patients with chronic migraine. Cephalalgia. 2022 Sep;42(10):1005-1012. doi: 10.1177/03331024221089567. Epub 2022 Mar 25.
PubMed 35332807
Ashina M, McAllister P, Cady R, Hirman J, Ettrup A. Efficacy and safety of eptinezumab in patients with migraine and self-reported aura: Post hoc analysis of PROMISE-1 and PROMISE-2. Cephalalgia. 2022 Jul;42(8):696-704. doi: 10.1177/03331024221077646. Epub 2022 Mar 18.
PubMed 35302389
Buse DC, Winner PK, Charleston L 4th, Hirman J, Cady R, Brevig T. Early response to eptinezumab indicates high likelihood of continued response in patients with chronic migraine. J Headache Pain. 2022 Feb 21;23(1):29. doi: 10.1186/s10194-022-01387-y.
PubMed 35189811
Martin V, Nagy AJ, Janelidze M, Giorgadze G, Hirman J, Cady R, Mehta L, Buse DC. Impact of Baseline Characteristics on the Efficacy and Safety of Eptinezumab in Patients With Migraine: Subgroup Analyses of PROMISE-1 and PROMISE-2. Clin Ther. 2022 Mar;44(3):389-402. doi: 10.1016/j.clinthera.2022.01.006. Epub 2022 Feb 5.
PubMed 35131090
Lipton RB, Charleston L 4th, Tassorelli C, Brevig T, Hirman J, Cady R. Patient-reported outcomes, health-related quality of life, and acute medication use in patients with a >/= 75% response to eptinezumab: subgroup pooled analysis of the PROMISE trials. J Headache Pain. 2022 Feb 7;23(1):23. doi: 10.1186/s10194-022-01386-z.
PubMed 35130836
Smith TR, Spierings ELH, Cady R, Hirman J, Ettrup A, Shen V. Cardiovascular outcomes in adults with migraine treated with eptinezumab for migraine prevention: pooled data from four randomized, double-blind, placebo-controlled studies. J Headache Pain. 2021 Nov 25;22(1):143. doi: 10.1186/s10194-021-01360-1.
PubMed 34823467
Smith TR, Spierings ELH, Cady R, Hirman J, Schaeffler B, Shen V, Sperling B, Brevig T, Josiassen MK, Brunner E, Honeywell L, Mehta L. Safety and tolerability of eptinezumab in patients with migraine: a pooled analysis of 5 clinical trials. J Headache Pain. 2021 Mar 30;22(1):16. doi: 10.1186/s10194-021-01227-5.
PubMed 33781209
Silberstein S, Diamond M, Hindiyeh NA, Biondi DM, Cady R, Hirman J, Allan B, Pederson S, Schaeffler B, Smith J. Eptinezumab for the prevention of chronic migraine: efficacy and safety through 24 weeks of treatment in the phase 3 PROMISE-2 (Prevention of migraine via intravenous ALD403 safety and efficacy-2) study. J Headache Pain. 2020 Oct 6;21(1):120. doi: 10.1186/s10194-020-01186-3.
PubMed 33023473
Lipton RB, Goadsby PJ, Smith J, Schaeffler BA, Biondi DM, Hirman J, Pederson S, Allan B, Cady R. Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology. 2020 Mar 31;94(13):e1365-e1377. doi: 10.1212/WNL.0000000000009169. Epub 2020 Mar 24.
PubMed 32209650

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Parallel Group, Double-Blind, Randomized, Placebo Controlled Phase 3 Trial to Evaluate the Efficacy and Safety of ALD403 Administered Intravenously in Patients With Chronic Migraine
ClinicalTrials.gov ID: NCT02974153
Acronym / sponsor ID: PROMISE 2 / ALD403-CLIN-011
Conditions: Migraine Disorders
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,121 participants (actual)
Lead sponsor: Alder Biopharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: Nov 2016 (actual)
Primary completion: Nov 2017 (actual)
Study completion: Apr 2018 (actual)
First posted: 28 Nov 2016 (estimated)
Results: Posted 9 Jun 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to assess the efficacy and safety of ALD403 in the prevention of migraine headache in chronic migraineurs.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
ALD403 (Eptinezumab) Dose Level 1	Experimental	Biological: ALD403 (Eptinezumab)ALD403 (Eptinezumab) Dose Level 1 (IV)
ALD403 (Eptinezumab) Dose Level 2	Experimental	Biological: ALD403 (Eptinezumab)ALD403 (Eptinezumab) Dose Level 2 (IV)
Placebo	Placebo comparator	Biological: PlaceboPlacebo (IV)

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Males and females between 18 and 65 years of age, inclusive, who were diagnosed with migraines at ≤ 50 years of age, and have a history of chronic migraine for ≥ 12 months before screening.
During the 28 day screening period, subjects must adequately complete the headache eDiary and must have headaches occurring on ≥ 15 to ≤ 26 days of which at least 8 must be migraine days.
Headache eDiary was completed on at least 24 of the 28 days prior to randomization.

Key exclusion criteria (6 listed)

Confounding and clinically significant pain syndromes (e.g. fibromyalgia, chronic low back pain, complex regional pain syndrome).
Psychiatric conditions that are uncontrolled and/or untreated, including conditions that are not controlled for a minimum of 6 months prior to screening. Patients with a lifetime history of psychosis, mania, or dementia are excluded.
Any use of botulinum toxin for migraine or for any other medical/cosmetic reasons requiring injections within 4 months prior to screening and during the screening period.
History or diagnosis of complicated migraine (ICHD-III beta version, 20134), chronic tension-type headache, hypnic headache, cluster headache, hemicrania continua, new daily persistent headache, or sporadic and familial hemiplegic migraine.
Receipt of any monoclonal antibody treatment (within or outside a clinical trial) within 6 months before 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
ALD403 (Eptinezumab)Also: Eptinezumab-jjmr, Vyepti	Biological	ALD403 (Eptinezumab) Dose Level 1, ALD403 (Eptinezumab) Dose Level 2
Placebo	Biological	Placebo

Primary outcome

Change From Baseline in Monthly Migraine Days
Time frame: Week 1-12
Monthly migraine days are summarized in 28-day intervals, and averaged across Weeks 1-12

26 secondary outcomes

75% Migraine Responder Rate
Time frame: Week 1-12
75% Migraine Responder Rate - 4 Week
Time frame: Week 1-4
50% Migraine Responder Rate
Time frame: Week 1-12
Percentage of Participants With a Migraine on the Day After Dosing
Time frame: Day 1
Change in Monthly Acute Medication Days
Time frame: Week 1-12
Change From Baseline of Headache Impact Test (HIT-6) Score
Time frame: Baseline to Week 12
Change in Migraine Prevalence From Baseline to Week 4
Time frame: Baseline to Week 4
75% Headache Responder Rate
Time frame: Week 1-12
50% Headache Responder Rate
Time frame: Week 1-12
100% Migraine Responder Rate
Time frame: Week 1-12
100% Headache Responder Rate
Time frame: Week 1-12
Change From Baseline in Monthly Migraine Days (Weeks 13-24)
Time frame: Week 13-24
Change From Baseline in Monthly Headache Days (Weeks 1-12)
Time frame: Week 1-12
Time to First Migraine After Dosing
Time frame: 32 weeks
Change From Baseline to Week 12 in Percentage of Migraines With Use of Acute Medication
Time frame: Week 1-12
Change From Baseline to Week 12 in Percentage of Headaches With Use of Acute Medication
Time frame: Week 1-12
Percent Change in Frequency of Migraine Days - Week 1-12
Time frame: Week 1-12
Percent Change in Frequency of Headache Days - Week 1-12
Time frame: Week 1-12
Change From Baseline in Percentage of Severe Migraines
Time frame: Week 1-12
Change From Baseline in Percentage of Severe Headache
Time frame: Week 1-12
Change From Baseline in Monthly Migraine Hours, Weeks 1-12
Time frame: Week 1-12
Change From Baseline in Monthly Headache Hours, Weeks 1-12
Time frame: Week 1-12
Duration of Migraine-Free Intervals
Time frame: 32 weeks
Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores
Time frame: Baseline to Week 12
Patient Global Impression of Change (PGIC) at Week 12
Time frame: Week 12
Health Related Quality of Life (EQ-5D-5L) at Week 12
Time frame: Week 12

Results and safety

Results posted to the registry on 9 Jun 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
300 mg ALD403	374	322
100 mg ALD403	372	324
Placebo	375	325

Primary outcome: Change From Baseline in Monthly Migraine Days

Time frame: Week 1-12. Mean (Full Range). Unit: Migraine Days

Measure	300 mg ALD403 n = 350	100 mg ALD403 n = 356	Placebo n = 366
Value	-8.2 (-23 to 11)	-7.7 (-22 to 10)	-5.6 (-25 to 9)

300 mg ALD403 vs Placebo: Mean Difference (Final Values): -2.60 (95% CI -3.45 to -1.74), p <0.0001, ANCOVA
100 mg ALD403 vs Placebo: Mean Difference (Final Values): -2.03 (95% CI -2.88 to -1.18), p <0.0001, ANCOVA

Population analysed: Full Analysis Population - all randomized participants who received investigational product or placebo

26 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline to Week 32 (end of study). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
300 mg ALD403	4 of 350 (1.1%)	52 of 350 (14.9%)	0 of 350
100 mg ALD403	3 of 356 (0.8%)	34 of 356 (9.6%)	0 of 356
Placebo	3 of 366 (0.8%)	42 of 366 (11.5%)	0 of 366

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39666143Tepper SJ, Diamond ML, Hirman J, Asher D, Fiore D, Cady R. Eptinezumab treatment was associated with longer interictal headache/migraine periods which corresponded to greater improvements in patient-reported quality of life measures. J Neurol. 2024 Dec 12;272(1):4. doi: 10.1007/s00415-024-12809-z.
Derived from this study: PubMed 37378754Kaniecki RG, Friedman DI, Asher D, Hirman J, Cady R. Improving to Four or Fewer Monthly Headache Days Per Month Provides a Clinically Meaningful Therapeutic Target for Patients with Chronic Migraine. Pain Ther. 2023 Oct;12(5):1179-1194. doi: 10.1007/s40122-023-00525-x. Epub 2023 Jun 28.
Derived from this study: PubMed 36284281Pozo-Rosich P, Dodick DW, Ettrup A, Hirman J, Cady R. Shift in diagnostic classification of migraine after initiation of preventive treatment with eptinezumab: post hoc analysis of the PROMISE studies. BMC Neurol. 2022 Oct 25;22(1):394. doi: 10.1186/s12883-022-02914-9.
Derived from this study: PubMed 36068494Cowan RP, Marmura MJ, Diener HC, Starling AJ, Schim J, Hirman J, Brevig T, Cady R. Quantity changes in acute headache medication use among patients with chronic migraine treated with eptinezumab: subanalysis of the PROMISE-2 study. J Headache Pain. 2022 Sep 6;23(1):115. doi: 10.1186/s10194-022-01482-0.
Derived from this study: PubMed 35436857Apelian R, Boyle L, Hirman J, Asher D. Measuring dose-related efficacy of eptinezumab for migraine prevention: post hoc analysis of PROMISE-1 and PROMISE-2. J Headache Pain. 2022 Apr 18;23(1):48. doi: 10.1186/s10194-022-01418-8.
Derived from this study: PubMed 35332807McAllister P, Kudrow D, Cady R, Hirman J, Ettrup A. Reduction in migraine-associated burden after eptinezumab treatment in patients with chronic migraine. Cephalalgia. 2022 Sep;42(10):1005-1012. doi: 10.1177/03331024221089567. Epub 2022 Mar 25.
Derived from this study: PubMed 35302389Ashina M, McAllister P, Cady R, Hirman J, Ettrup A. Efficacy and safety of eptinezumab in patients with migraine and self-reported aura: Post hoc analysis of PROMISE-1 and PROMISE-2. Cephalalgia. 2022 Jul;42(8):696-704. doi: 10.1177/03331024221077646. Epub 2022 Mar 18.
Derived from this study: PubMed 35189811Buse DC, Winner PK, Charleston L 4th, Hirman J, Cady R, Brevig T. Early response to eptinezumab indicates high likelihood of continued response in patients with chronic migraine. J Headache Pain. 2022 Feb 21;23(1):29. doi: 10.1186/s10194-022-01387-y.
Derived from this study: PubMed 35131090Martin V, Nagy AJ, Janelidze M, Giorgadze G, Hirman J, Cady R, Mehta L, Buse DC. Impact of Baseline Characteristics on the Efficacy and Safety of Eptinezumab in Patients With Migraine: Subgroup Analyses of PROMISE-1 and PROMISE-2. Clin Ther. 2022 Mar;44(3):389-402. doi: 10.1016/j.clinthera.2022.01.006. Epub 2022 Feb 5.
Derived from this study: PubMed 35130836Lipton RB, Charleston L 4th, Tassorelli C, Brevig T, Hirman J, Cady R. Patient-reported outcomes, health-related quality of life, and acute medication use in patients with a >/= 75% response to eptinezumab: subgroup pooled analysis of the PROMISE trials. J Headache Pain. 2022 Feb 7;23(1):23. doi: 10.1186/s10194-022-01386-z.
Derived from this study: PubMed 34823467Smith TR, Spierings ELH, Cady R, Hirman J, Ettrup A, Shen V. Cardiovascular outcomes in adults with migraine treated with eptinezumab for migraine prevention: pooled data from four randomized, double-blind, placebo-controlled studies. J Headache Pain. 2021 Nov 25;22(1):143. doi: 10.1186/s10194-021-01360-1.
Derived from this study: PubMed 33781209Smith TR, Spierings ELH, Cady R, Hirman J, Schaeffler B, Shen V, Sperling B, Brevig T, Josiassen MK, Brunner E, Honeywell L, Mehta L. Safety and tolerability of eptinezumab in patients with migraine: a pooled analysis of 5 clinical trials. J Headache Pain. 2021 Mar 30;22(1):16. doi: 10.1186/s10194-021-01227-5.

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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.

The record lists no contact. Use the official record to reach the sponsor.

144 sites in 13 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ALD403 (Eptinezumab) in people with Migraine Disorders, run by Alder Biopharmaceuticals, Inc. at 144 sites in 13 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 3 inclusion and 6 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 9 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 144 sites in United States, Spain, Russia, Ukraine, Italy and 8 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 9 Jun 2020). 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 (time frame: Week 1-12). 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 NCT02974153, which also lists 14 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 9 Jun 2020.