A Study to Evaluate the Efficacy and Safety of Eptinezumab Administered Intravenously in Participants Experiencing Acute Attack of Migraine (RELIEF)

A Parallel Group, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Eptinezumab Administered Intravenously in Subjects Experiencing an Acute Attack of Migraine

The purpose of this study is to evaluate the efficacy and safety of eptinezumab administered intravenously in participants experiencing an acute attack of migraine.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Eptinezumab; Drug: Placebo

Detailed Description

This will be a parallel group, double-blind, randomized, placebo-controlled study assessing the efficacy of eptinezumab for acute migraine, defined as an active intercurrent migraine occurring in those participants who are candidates for preventive therapy. Participants will be randomized to receive a single dose of eptinezumab or placebo in a 1:1 ratio. The total study duration will be approximately 4 to 12 weeks, including up to an 8-week screening period and 4-week of safety follow-up, with clinic visits occurring on Screening, Day 0 (dosing day), and Week 4.

• Study Type: Interventional
• Enrollment (Actual): 485
• Phase: Phase 3

Contacts and Locations

Study Locations

• Georgia
  • Tbilisi, Georgia
    • Ltd "Acad Fridon Todua Medical Center - Ltd Research Institute of Clinical Medicine"
  • Tbilisi, Georgia
    • Ltd "Aversi Clinic"
  • Tbilisi, Georgia
    • Ltd "Multiprofile Clinica Consilium Medulla"
  • Tbilisi, Georgia
    • LTD Simon Khechinashvili University Clinic
  • Tbilisi, Georgia
    • td "Israel-Georgia Medical Research Clinic Helsicore"
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Alabama Clinical Therapeutics
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Arizona Research Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Baptist Health Center for Clinical Research
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center
    • Carlsbad, California, United States, 92011
      • The Neurology Center of Southern California - Carlsbad
    • Oceanside, California, United States, 92056
      • Excell Research Inc
    • Redlands, California, United States, 92374
      • Anderson Clinical Research
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
    • Denver, Colorado, United States, 80210
      • Denver Neurological Clinic - Denver
  • Connecticut
    • New London, Connecticut, United States, 06320
      • Coastal Connecticut Research LLC
    • Stamford, Connecticut, United States, 06905
      • Ki Health Partners LLC, dba New England Institute for Clinical Research
  • District of Columbia
    • Washington, District of Columbia, United States, 20052
      • The George Washington Medical Faculty Associates
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • Medicinae Doctor Clinical
    • Hialeah, Florida, United States, 33012
      • AGA Clinical Trials
    • Maitland, Florida, United States, 32751
      • Meridien Research - Maitland
    • West Palm Beach, Florida, United States, 33407
      • Palm Beach Neurology and Premiere Research Institute
    • Winter Haven, Florida, United States, 33880
      • Clinical Research of Central Florida
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Office of Doctor Frank Berenson
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta, LLC
    • Savannah, Georgia, United States, 31405
      • Meridian Clinical Research - Savannah Neurology Specialists
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Cedar Crosse Research Center
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • College Park Family Care Center Physicians
    • Prairie Village, Kansas, United States, 66208
      • Phoenix Medical Research
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • Waltham, Massachusetts, United States, 02451
      • MedVadis Research Corporation, LLC
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Michigan Head Pain and Neurological Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute - Minneapolis
  • Mississippi
    • Ridgeland, Mississippi, United States, 39157
      • Headache Neurology Research Institute
  • Missouri
    • Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
    • Springfield, Missouri, United States, 65810
      • Clinvest Research
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Nevada Headache Institute
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuqerque Clinical Trials
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute - Amherst
    • Brooklyn, New York, United States, 11229
      • Integrative Clinical Trials
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
    • Columbus, Ohio, United States, 43213
      • Aventiv Research - Columbus
    • Dayton, Ohio, United States, 45424
      • Hometown Urgent Care and Research - Huber Heights
    • North Canton, Ohio, United States, 44720
      • Neuro-Behavioral Clinical Research Inc
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74133
      • DelRicht Research
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network
  • Pennsylvania
    • Smithfield, Pennsylvania, United States, 15478
      • Frontier Clinical Rsearch LLC
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center - Mount Pleasant
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-ClinSearch LLC
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Medical Research LLC
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group - Kingsport
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Ventavia Research Group, LLC
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development Inc
    • Keller, Texas, United States, 76248
      • Ventavia Research Group, LLC
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • J. Lewis Research, Inc. / Foothill Family Clinic
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
  • Wisconsin
    • Neenah, Wisconsin, United States, 54956
      • Neuroscience Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Greater than 1-year history of migraine, with or without aura, with onset of first migraine before age 50.
• Migraine on 4 to 15 days per month in the 3 months prior to screening.
• Headache free for at least 24 hours prior to onset of a qualifying migraine.

Exclusion Criteria:

• Unable to differentiate migraine from other headache or pain disorders.

• Use of the following medication, for any indication, within the 24-hour period prior to dosing with study drug:

  1. triptans, ergotamines and ergot-derivatives
  2. analgesics (including but not limited to acetaminophen, tramadol, nonsteroidal anti-inflammatory drugs [NSAIDs], combination analgesics, caffeine-containing analgesics, and opioids/narcotics) and other acute migraine medication(s)
  3. antiemetic medications (including but not limited to prochlorperazine, promethazine, droperidol, chlorpromazine, metoclopramide)
  4. antihistamines
  5. devices, neuromodulation, neurostimulation, or injectable therapy (trigger point injections, extracranial nerve blocks, facet joint injections, spinal manipulation)

• Use of the following medication, for any indication, in each of the 3 months prior to screening:

  1. opioids/narcotics or butalbital containing products (including combinations) on more than 4 days per month;
  2. triptans, ergotamines, or combination analgesics for 10 or more days per month;
  3. acetaminophen, aspirin or NSAIDs for 15 or more days per month (except if participant is taking 81 mg dose of aspirin for cardiac prophylaxis)
• History or diagnosis of chronic tension-type headache, hypnic headache, cluster headache, hemicrania continua, new daily persistent headache, or unusual migraine subtypes such as hemiplegic migraine (sporadic and familial), ophthalmoplegic migraine and migraine with neurological accompaniments that are not typical of migraine aura (for example, diplopia, altered consciousness, or long duration).
• Any changes to preventive migraine treatment(s) within 1 month prior to screening and up to treatment with the study drug (Day 0).
• Any use of approved devices, neuromodulation, neurostimulation, or injectable therapy (trigger point injections, extracranial nerve blocks, facet joint injections) within the 24-hour period prior to treatment with study drug (Day 0).
• Any use of botulinum toxin for migraine or for any other medical/cosmetic reasons requiring injections within 7 days prior to treatment with study drug (Day 0).
• Any use of systemic corticosteroid for migraine or any other reason within 3 months prior to treatment with study drug (Day 0).
• Evidence or medical history of clinically significant psychiatric diseases that are uncontrolled and/or untreated.
• Receipt of any monoclonal antibody treatment, for migraine or any other indication, (within or outside a clinical study) within 6 months prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eptinezumab; Participants will receive a single dose of eptinezumab 100 milligrams (mg) administered via intravenous (IV) infusion on Day 0.	Drug: Eptinezumab; Injection for IV administration
Placebo Comparator: Placebo; Participants will receive a single dose of placebo matching to eptinezumab administered via IV infusion on Day 0.	Drug: Placebo; Injection for IV administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Headache Pain Freedom	Time to headache pain freedom defined as the time that the participant reported freedom of pain, meaning their headache pain had gone from moderate to severe at baseline to no pain.	Up to 48 hours postdose
Time to Absence of Most Bothersome Symptom (MBS)	Time to absence of most bothersome symptom defined as the time that the participant reported absence of MBS (of nausea, photophobia, or phonophobia).	Up to 48 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Headache Pain Freedom at 2 Hours	Number of participants with freedom from headache pain at 2 hours postdose are reported. Freedom from headache pain meaning that the headache pain that had gone from moderate to severe at baseline to no pain with no administration of rescue medications.	2 hours
Absence of MBS at 2 Hours	Number of participants with absence of MBS (of nausea, photophobia, or phonophobia) at 2 hours postdose are reported.	2 hours
Headache Pain Freedom at 4 Hours	Number of participants with freedom from headache pain at 4 hours postdose are reported. Freedom from headache pain meaning that the headache pain that had gone from moderate to severe at baseline to no pain with no administration of rescue medications.	4 hours
Absence of MBS at 4 Hours	Number of participants with absence of MBS (of nausea, photophobia, or phonophobia) at 4 hours postdose are reported.	4 hours
Use of Rescue Medication Within the First 24 Hours	Rescue medication was defined as any medication to treat migraine or migraine-associated symptoms, which could have been provided to the participant any time after 2 hours post-start of infusion. Use of rescue medication was captured in the eDiary. Number of participants who used rescue medication up to 24 hours postdose are reported.	Up to 24 hours postdose

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S
• Collaborators: Alder Biopharmaceuticals, Inc.

Publications and helpful links

General Publications

• Cady R, Lipton RB, Buse DC, Josiassen MK, Lindsten A, Ettrup A. Optimization of acute medication use following eptinezumab initiation during a migraine attack: post hoc analysis of the RELIEF study. J Headache Pain. 2022 Jul 28;23(1):91. doi: 10.1186/s10194-022-01463-3.
• Ailani J, McAllister P, Winner PK, Chakhava G, Krog Josiassen M, Lindsten A, Sperling B, Ettrup A, Cady R. Rapid resolution of migraine symptoms after initiating the preventive treatment eptinezumab during a migraine attack: results from the randomized RELIEF trial. BMC Neurol. 2022 Jun 3;22(1):205. doi: 10.1186/s12883-022-02714-1.
• McAllister P, Winner PK, Ailani J, Buse DC, Lipton RB, Chakhava G, Josiassen MK, Lindsten A, Mehta L, Ettrup A, Cady R. Eptinezumab treatment initiated during a migraine attack is associated with meaningful improvement in patient-reported outcome measures: secondary results from the randomized controlled RELIEF study. J Headache Pain. 2022 Feb 7;23(1):22. doi: 10.1186/s10194-021-01376-7.
• Winner PK, McAllister P, Chakhava G, Ailani J, Ettrup A, Krog Josiassen M, Lindsten A, Mehta L, Cady R. Effects of Intravenous Eptinezumab vs Placebo on Headache Pain and Most Bothersome Symptom When Initiated During a Migraine Attack: A Randomized Clinical Trial. JAMA. 2021 Jun 15;325(23):2348-2356. doi: 10.1001/jama.2021.7665.

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2019
• Primary Completion (Actual): July 8, 2020
• Study Completion (Actual): July 8, 2020

Study Registration Dates

• First Submitted: November 2, 2019
• First Submitted That Met QC Criteria: November 2, 2019
• First Posted (Actual): November 5, 2019

Study Record Updates

• Last Update Posted (Actual): August 17, 2021
• Last Update Submitted That Met QC Criteria: August 13, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: ALD403-CLIN-015; 18903A (Other Identifier: H. Lundbeck A/S)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No