MigrainePhase 2NCT04498910
A Study of LY3451838 in Participants With Migraine
A Phase 2 study testing LY3451838 in people with Migraine, run by Eli Lilly and Company at 9 sites in United States.
Trial summary
The reason for this study is to see if the study drug LY3451838 is safe and effective in participants who have migraine that have not responded to other preventive treatments. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Migraine
- What is being tested?
- LY3451838
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 9 sitesUnited States
- Study dates
- 16 Nov 2020to 9 Nov 2022
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have a diagnosis of migraine with a history of migraine headaches of at least 1 year prior, and migraine onset prior to age 50.
- Have completed at least 80% of required daily diary entries during the start of the study.
- Have documentation of previous failure of 2 to 4 standard-of-care migraine preventive medication categories in the past 10 years.
- Women of child-bearing potential must test negative for pregnancy as indicated by a negative serum pregnancy test and negative urine pregnancy test.
- Women of child-bearing potential who are abstinent or in a same sex relationship must agree to either remain abstinent or to avoid sexual relationships with males.
- Women of child-bearing potential who are not abstinent, must agree to use one highly effective method of contraception, or a combination of two effective methods of contraception during the study, as well as 5 months following.
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- Women not of childbearing potential may participate and include those who are: A. Infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy or tubal ligation) or congenital anomaly; or B. Post-menopausal - defined as either:
- i. a woman at least 40 years of age with an intact uterus, not on hormone therapy, who has cessation of menses for at least 1 year without an alternative medical cause, and a follicle-stimulating hormone greater than (>) 40 multi-international units per milliliter (mIU/mL); or
- ii. a woman 55 or older not on hormone therapy, who has had at least 12 months of spontaneous amenorrhea; or
- iii. a woman at least 55 years of age with a diagnosis of menopause prior to starting hormone replacement therapy
Who cannot join
- Are currently enrolled in any other clinical study or any other type of medical research judged not to be compatible with this study.
- Have participated, within the last 30 days or 5-half-lives (whichever is longer), in a clinical study involving any investigational product. If the half-life of the investigational product is unknown, 6 months should have passed prior.
- Known hypersensitivity or intolerance to monoclonal antibodies or other therapeutic proteins, or to common antihistamines, epinephrine, methyl prednisone or other systemic corticosteroids.
- Are currently receiving medication or other treatment for prevention of migraine headaches. Participants must have discontinued such medications or treatments at least 2 weeks prior. Botulinum toxin A or B that has been administered in the head or neck area use must be discontinued at least 3 months prior. Nerve blocks or device use (such as transcranial magnetic stimulation or electrical nerve stimulation) in the head or neck area for migraine treatment must be discontinued at least 30 days prior. Anti-calcitonin gene-related peptide (CGRP) antibodies must be discontinued at least 5 half-lives prior.
- Have previously failed more than 4 migraine preventive medication categories in the past 10 years due to inadequate efficacy (that is, maximum tolerated dose for at least 2 months) and/or safety / tolerability reasons.
- History of cluster headache or migraine subtypes including hemiplegic (sporadic or familial) migraine, ophthalmoplegic migraine, retinal migraine, typical aura without headache, complications of migraine and migraine with brainstem aura (basilar-type migraine).
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- In the 3 months prior, have other types of headache besides migraine, tension type headache, or medication overuse headache (MOH). (In other words, participants can have migraine, tension type headache, or MOH in the 3 months prior, but they cannot have other types of headache in that time).
- History of head or neck injury within last 6 months.
- History of traumatic cervical or head injury associated with significant change in the quality or frequency of headaches.
- Have reading of electrocardiogram (ECG) showing abnormalities considered incompatible with the study.
- Any liver tests outside the normal range.
- Evidence of significant active or unstable psychiatric disease.
- Women who are pregnant or nursing.
- Participants who have used opioids or barbiturate-containing analgesic >4 days per month for the treatment of pain in each of the past 3 months.
- History of drug or alcohol abuse/dependence within 1 year.
- Have a positive urine drug screen for illicit drugs.
- Are unwilling or unable to comply with the use of data collection devices.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
StudyMetrix Research
City of Saint Peters, Missouri, 63303
Health Research of Hampton Roads Inc
Newport News, Virginia, 23606
Renstar Medical Research
Ocala, Florida, 34470
Emerald Coast Center for Neurological Disorders
Pensacola, Florida, 32504
21st Century Neurology, a division of Xenoscience
Phoenix, Arizona, 85004-0000
Clinvest Research LLC
Springfield, Missouri, 65810
New England Institute for Clinical Research
Stamford, Connecticut, 06905
University of South Florida
Tampa, Florida, 33612-4799
Bio Behavioral Health
Toms River, New Jersey, 08755
About this study
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of LY3451838 in Adults With Treatment-Resistant Migraine
The reason for this study is to see if the study drug LY3451838 is safe and effective in participants who have migraine that have not responded to other preventive treatments.
- Conditions
- Migraine
- Being tested
- LY3451838, 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.
LY3451838Drug
Administered IV
PlaceboDrug
Administered IV
| Study group | Role | What they receive |
|---|---|---|
| 1500 milligrams (mg) LY3451838 | Experimental | Participants received a single intravenous (IV) dose of 1500 mg LY3451838. Receives: Drug: LY3451838 |
| Placebo | Placebo comparator | Participants received a single IV dose of placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in the Number of Monthly Migraine Headache Days During 1-Month
Migraine Headache Day is a calendar day on which a migraine or probable migraine headache occurs. Per International Headache Society [IHS] International Classification of Headache Disorders version 3 [ICHD-3], migraine is defined as a headache, with or without aura, of >=30 minutes duration with both of the following required features (A) At least 2 of the following headache characteristics: Unilateral location; Pulsatile quality; Moderate or severe pain intensity; Aggravation by or causing avoidance of routine physical activity (B) During headache at least 1 of the following: Nausea and/or vomiting; Photophobia and phonophobia. Least square mean was assessed using Bayesian Mixed Model Analysis with baseline number of monthly migraine headache days as a covariate.
Measured: Baseline, Month 1
Secondary outcomes (6)
Change From Baseline in the Number of Monthly Headache Days During 3-Month
Migraine Headache Day is a calendar day on which a migraine or probable migraine headache occurs. Per International Headache Society [IHS] International Classification of Headache Disorders version 3 [ICHD-3], migraine is defined as a headache, with or without aura, of >=30 minutes duration with both of the following required features (A) At least 2 of the following headache characteristics: Unilateral location; Pulsatile quality; Moderate or severe pain intensity; Aggravation by or causing avoidance of routine physical activity (B) During headache at least 1 of the following: Nausea and/or vomiting; Photophobia and phonophobia. Least square mean was assessed using Bayesian Mixed Model Analysis with baseline number of monthly migraine headache days as a covariate.
Measured: Baseline, Month 3
Percentage of Participants With ≥50% Reduction From Baseline in Monthly Migraine Headache Days
Percentage of Participants with ≥50% Reduction from Baseline in Monthly Migraine Headache Days are reported.
Measured: Month 1
Number of Participants With at Least One Treatment-emergent Adverse Events (TEAEs)
Number of Participants with at least one TEAEs are reported. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Measured: Baseline up to 5 Months
Number of Participants With at Least One Serious Adverse Events (SAEs)
Number of Participants with at least one SAEs are reported. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Measured: Baseline up to 5 Months
Pharmacokinetics (PK): Area Under the Serum Concentration-time Curve From Time 0 to the Last Measurable Serum Concentration (AUC 0-t) of LY3451838
PK: AUC(0-t) of LY3451838
Measured: Pre-infusion, end of infusion, 3hours(h), 365h, 730h, 1095h, 1460h, 1825h, 2190h, 2920h, 3650h post-infusion
PK: Maximum Observed Serum Concentration (Cmax) of LY3451838
PK: Cmax of LY3451838
Measured: Pre-infusion, end of infusion, 3hours(h), 365h, 730h, 1095h, 1460h, 1825h, 2190h, 2920h, 3650h post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2020
- Study start16 Nov 2020
- Primary completion9 Nov 2022
- Study completion9 Nov 2022
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 (1)Papers the sponsor has linked to this study.
- Other trials for MigraineStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04498910
- Sponsor's protocol ID
- 17124
- Other IDs
- J1H-MC-LAJB
- Status last verified
- Nov 2023
- First submitted
- 3 Aug 2020
- Last updated
- 28 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Publications
Johnson MP, Krikke-Workel J, Patel CN, Morin SM, Turner PK, Clark KA, Donley D, Jin Y, Johnson KW, Vincent M, Stille JR, Broad LM, Patel A. Preclinical and clinical evaluation of LY3451838, a PACAP-neutralizing monoclonal antibody, in randomized, double-blind, placebo-controlled phase 1 and phase 2 studies involving healthy adults and adults with treatment-resistant migraine. Cephalalgia. 2025 Aug;45(8):3331024251368757. doi: 10.1177/03331024251368757. Epub 2025 Aug 21.
PubMed 40836866
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of LY3451838 in Adults With Treatment-Resistant Migraine
- ClinicalTrials.gov ID
- NCT04498910
- Acronym / sponsor ID
- 17124
- Conditions
- Migraine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- 16 Nov 2020 (actual)
- Primary completion
- 9 Nov 2022 (actual)
- Study completion
- 9 Nov 2022 (actual)
- First posted
- 5 Aug 2020 (actual)
- Results
- Posted 28 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The reason for this study is to see if the study drug LY3451838 is safe and effective in participants who have migraine that have not responded to other preventive treatments.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1500 milligrams (mg) LY3451838 | Experimental | Drug: LY3451838Participants received a single intravenous (IV) dose of 1500 mg LY3451838. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants received a single IV dose of placebo. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Must have a diagnosis of migraine with a history of migraine headaches of at least 1 year prior, and migraine onset prior to age 50.
- Have completed at least 80% of required daily diary entries during the start of the study.
- Have documentation of previous failure of 2 to 4 standard-of-care migraine preventive medication categories in the past 10 years.
- Women of child-bearing potential must test negative for pregnancy as indicated by a negative serum pregnancy test and negative urine pregnancy test.
- Women of child-bearing potential who are abstinent or in a same sex relationship must agree to either remain abstinent or to avoid sexual relationships with males.
Key exclusion criteria (17 listed)
- Are currently enrolled in any other clinical study or any other type of medical research judged not to be compatible with this study.
- Have participated, within the last 30 days or 5-half-lives (whichever is longer), in a clinical study involving any investigational product. If the half-life of the investigational product is unknown, 6 months should have passed prior.
- Known hypersensitivity or intolerance to monoclonal antibodies or other therapeutic proteins, or to common antihistamines, epinephrine, methyl prednisone or other systemic corticosteroids.
- Are currently receiving medication or other treatment for prevention of migraine headaches. Participants must have discontinued such medications or treatments at least 2 weeks prior. Botulinum toxin A or B that has been administered in the head or neck area use must be discontinued at least 3 months prior. Nerve blocks or device use (such as transcranial magnetic stimulation or electrical nerve stimulation) in the head or neck area for migraine treatment must be discontinued at least 30 days prior. Anti-calcitonin gene-related peptide (CGRP) antibodies must be discontinued at least 5 half-lives prior.
- Have previously failed more than 4 migraine preventive medication categories in the past 10 years due to inadequate efficacy (that is, maximum tolerated dose for at least 2 months) and/or safety / tolerability reasons.
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 |
|---|---|---|
| LY3451838Administered IV | Drug | 1500 milligrams (mg) LY3451838 |
| PlaceboAdministered IV | Drug | Placebo |
Primary outcome
Change From Baseline in the Number of Monthly Migraine Headache Days During 1-Month
Time frame: Baseline, Month 1
Migraine Headache Day is a calendar day on which a migraine or probable migraine headache occurs. Per International Headache Society [IHS] International Classification of Headache Disorders version 3 [ICHD-3], migraine is defined as a headache, with or without aura, of >=30 minutes duration with both of the following required features (A) At least 2 of the following headache characteristics: Unilateral location; Pulsatile quality; Moderate or severe pain intensity; Aggravation by or causing avoidance of routine physical activity (B) During headache at least 1 of the following: Nausea and/or vomiting; Photophobia and phonophobia. Least square mean was assessed using Bayesian Mixed Model Analysis with baseline number of monthly migraine headache days as a covariate.
6 secondary outcomes
Change From Baseline in the Number of Monthly Headache Days During 3-Month
Time frame: Baseline, Month 3
Percentage of Participants With ≥50% Reduction From Baseline in Monthly Migraine Headache Days
Time frame: Month 1
Number of Participants With at Least One Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline up to 5 Months
Number of Participants With at Least One Serious Adverse Events (SAEs)
Time frame: Baseline up to 5 Months
Pharmacokinetics (PK): Area Under the Serum Concentration-time Curve From Time 0 to the Last Measurable Serum Concentration (AUC 0-t) of LY3451838
Time frame: Pre-infusion, end of infusion, 3hours(h), 365h, 730h, 1095h, 1460h, 1825h, 2190h, 2920h, 3650h post-infusion
PK: Maximum Observed Serum Concentration (Cmax) of LY3451838
Time frame: Pre-infusion, end of infusion, 3hours(h), 365h, 730h, 1095h, 1460h, 1825h, 2190h, 2920h, 3650h post-infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40836866Johnson MP, Krikke-Workel J, Patel CN, Morin SM, Turner PK, Clark KA, Donley D, Jin Y, Johnson KW, Vincent M, Stille JR, Broad LM, Patel A. Preclinical and clinical evaluation of LY3451838, a PACAP-neutralizing monoclonal antibody, in randomized, double-blind, placebo-controlled phase 1 and phase 2 studies involving healthy adults and adults with treatment-resistant migraine. Cephalalgia. 2025 Aug;45(8):3331024251368757. doi: 10.1177/03331024251368757. Epub 2025 Aug 21.
- A Study of LY3451838 in Participants With MigraineLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
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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.
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) study director
Eli Lilly and Company
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LY3451838 in people with Migraine, run by Eli Lilly and Company at 9 sites in United States.
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 10 inclusion and 17 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 28 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. 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 28 Nov 2023). 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 the Number of Monthly Migraine Headache Days During 1-Month (time frame: Baseline, Month 1). 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 NCT04498910, which also lists 1 linked publication.
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 28 Nov 2023.