A Study of LY3451838 in Participants With Migraine

NCT04498910 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 17124J1H-MC-LAJB
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Migraine

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, Month 1

Secondary Outcomes (6)

• Change From Baseline in the Number of Monthly Headache Days During 3-Month

  Baseline, Month 3

• Percentage of Participants With ≥50% Reduction From Baseline in Monthly Migraine Headache Days

  Month 1

• Number of Participants With at Least One Treatment-emergent Adverse Events (TEAEs)

  Baseline up to 5 Months

• Number of Participants With at Least One Serious Adverse Events (SAEs)

  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

  Pre-infusion, end of infusion, 3hours(h), 365h, 730h, 1095h, 1460h, 1825h, 2190h, 2920h, 3650h post-infusion

Study Arms (2)

1500 milligrams (mg) LY3451838

EXPERIMENTAL

Participants received a single intravenous (IV) dose of 1500 mg LY3451838.

Drug: LY3451838

Placebo

PLACEBO COMPARATOR

Participants received a single IV dose of placebo.

Drug: Placebo

Interventions

LY3451838 DRUG

Administered IV

1500 milligrams (mg) LY3451838

Placebo DRUG

Administered IV

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (9)

21st Century Neurology, a division of Xenoscience

Phoenix, Arizona, 85004-0000, United States

Location

New England Institute for Clinical Research

Stamford, Connecticut, 06905, United States

Location

Renstar Medical Research

Ocala, Florida, 34470, United States

Location

Emerald Coast Center for Neurological Disorders

Pensacola, Florida, 32504, United States

Location

University of South Florida

Tampa, Florida, 33612-4799, United States

Location

StudyMetrix Research

City of Saint Peters, Missouri, 63303, United States

Location

Clinvest Research LLC

Springfield, Missouri, 65810, United States

Location

Bio Behavioral Health

Toms River, New Jersey, 08755, United States

Location

Health Research of Hampton Roads Inc

Newport News, Virginia, 23606, United States

Location

Related Publications (1)

• 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.

  PMID: 40836866 DERIVED

Related Links

• A Study of LY3451838 in Participants With Migraine

MeSH Terms

Conditions

Migraine Disorders

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

08005455979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2020
• First Posted: August 5, 2020
• Study Start: November 16, 2020
• Primary Completion: November 9, 2022
• Study Completion: November 9, 2022
• Last Updated: November 28, 2023
• Results First Posted: November 28, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

US (9)