A Multicenter Assessment of ALD403 in Chronic Migraine

A Parallel Group, Double-Blind, Randomized, Placebo Controlled, Dose-Ranging Phase 2 Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of ALD403 Administered Intravenously in Patients With Chronic Migraine

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

Study Overview

• Status: Completed
• Conditions: Migraine Disorders
• Intervention / Treatment: Biological: Placebo; Biological: ALD403

• Study Type: Interventional
• Enrollment (Actual): 665
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2031
      • Research Site
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Research Site
    • Melbourne, Victoria, Australia, 3050
      • Research Site
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Research Site
• Georgia
  • Tbilisi, Georgia, 0160
    • Research Site
  • Tbilisi, Georgia, 0186
    • Research Site
  • Tbilisi, Georgia, 0112
    • Research Site
• New Zealand
  • Auckland, New Zealand, 8963
    • Research Site
  • Christchurch, New Zealand, 2856
    • Research Site
  • Hamilton, New Zealand, 3204
    • Research Site
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Research Site
    • Mobile, Alabama, United States, 36608
      • Research Site
  • Arizona
    • Phoenix, Arizona, United States, 85027
      • Research Site
    • Scottsdale, Arizona, United States, 85259
      • Research Site
  • Arkansas
    • Hot Springs, Arkansas, United States, 71901
      • Research Site
    • Little Rock, Arkansas, United States, 72211
      • Research Site
  • California
    • Anaheim, California, United States, 92801
      • Research Site
    • Encino, California, United States, 91436
      • Research Site
    • Long Beach, California, United States, 90806
      • Reserach Site
    • Los Angeles, California, United States, 90036
      • Research Site
    • Oakland, California, United States, 94612
      • Research Site
    • San Diego, California, United States, 92108
      • Research Site
    • San Francisco, California, United States, 94102
      • Research Site
    • Santa Monica, California, United States, 90404
      • Research Site
    • Stanford, California, United States, 94305
      • Research Site
    • Ventura, California, United States, 93003
      • Research Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80918
      • Research Site
    • Denver, Colorado, United States, 80210
      • Research Site
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Research Site
    • Waterbury, Connecticut, United States, 06708
      • Research Site
  • Florida
    • Gainesville, Florida, United States, 32607
      • Research Site
    • Hallandale Beach, Florida, United States, 33009
      • Research Site
    • Jacksonville, Florida, United States, 32256
      • Research Site
    • Miami, Florida, United States, 33173
      • Research Site
    • Miami, Florida, United States, 33144
      • Research Site
    • North Miami, Florida, United States, 33161
      • Research Site
    • Orlando, Florida, United States, 32806
      • Research Site
    • Orlando, Florida, United States, 32801
      • Research Site
    • Tampa, Florida, United States, 33606
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Research Site
    • Atlanta, Georgia, United States, 30022
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Research Site
    • Chicago, Illinois, United States, 60640
      • Research Site
    • Evansville, Illinois, United States, 47714
      • Research Site
    • Normal, Illinois, United States, 61761
      • Research Site
  • Kansas
    • Prairie Village, Kansas, United States, 66206
      • Research Site
    • Wichita, Kansas, United States, 67207
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Research Site
    • Shreveport, Louisiana, United States, 71105
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 21310
      • Research Site
    • Brockton, Massachusetts, United States, 02301
      • Research Site
    • New Bedford, Massachusetts, United States, 02740
      • Research Site
    • Watertown, Massachusetts, United States, 02472
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Research Site
    • Springfield, Missouri, United States, 65807
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Research Site
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Research Site
  • New York
    • Albany, New York, United States, 12208
      • Research Site
    • Amherst, New York, United States, 14226
      • Research Site
    • Bronx, New York, United States, 10461
      • Research Site
    • Brooklyn, New York, United States, 11235
      • Research Site
    • Endwell, New York, United States, 13760
      • Research Site
    • New York, New York, United States, 10019
      • Research Site
    • Rochester, New York, United States, 14609
      • Research Site
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Research Site
    • Winston-Salem, North Carolina, United States, 27103
      • Research Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • Research Site
    • Cincinnati, Ohio, United States, 45255
      • Research Site
    • Cleveland, Ohio, United States, 44195
      • Research Site
    • Columbus, Ohio, United States, 43213
      • Research Site
    • Dayton, Ohio, United States, 45424
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Research Site
    • Willow Grove, Pennsylvania, United States, 19090
      • Research Site
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Research Site
    • Memphis, Tennessee, United States, 38119
      • Research Site
  • Texas
    • Austin, Texas, United States, 78705
      • Research Site
    • Dallas, Texas, United States, 75231
      • Research Site
    • Fort Worth, Texas, United States, 76104
      • Research Site
    • Houston, Texas, United States, 77058
      • Research Site
  • Utah
    • Orem, Utah, United States, 84058
      • Research Site
    • Salt Lake City, Utah, United States, 84109
      • Research Site
  • Virginia
    • Richmond, Virginia, United States, 23226
      • Research Site
    • Virginia Beach, Virginia, United States, 23454
      • Research Site
  • Washington
    • Bellevue, Washington, United States, 98007
      • Research Site
    • Seattle, Washington, United States, 98105
      • Research Site
    • Tacoma, Washington, United States, 98405
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of migraine at ≤ 35 years of age with history of chronic migraine ≥ 1 year
• During the 28 day screening period, must have ≥ 15 headache days of which ≥ 8 days were assessed as migraine days with at least 5 migraine attacks as recorded in the eDiary
• Headache eDiary was completed on at least 22 of the 28 days prior to randomization

Exclusion Criteria:

• Confounding pain syndromes (e.g. fibromyalgia, chronic low back pain, complex regional pain syndrome) or any pain syndrome that requires regular analgesia
• Psychiatric conditions that are uncontrolled and untreated, including conditions that are not controlled for a minimum of 6 months prior to screening.
• History or diagnosis of complicated migraine (ICHD-III beta version, 2013), chronic tension-type headache, hypnic headache, cluster headache, hemicrania continua, new daily persistent headache, migraine with brainstem aura, sporadic and familial hemiplegic migraine
• Unable to differentiate migraine from other headaches
• Subject has received botulinum toxin for migraine or for any other medical/cosmetic reasons requiring injections in the head, face, or neck within 4 months prior to screening.
• Have any clinically significant concurrent medical condition
• Receipt of any monoclonal antibody treatment within 6 months of screening (within or outside a clinical trial)
• Previously dosed with ALD403 or any monoclonal antibody targeting the CGRP pathway

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALD403 Dose Level 1; ALD403 Dose Level 1 (IV)	Biological: ALD403; Other Names: Eptinezumab-jjmr; Vyepti
Experimental: ALD403 Dose Level 2; ALD403 Dose Level 2 (IV)	Biological: ALD403; Other Names: Eptinezumab-jjmr; Vyepti
Experimental: ALD403 Dose Level 3; ALD403 Dose Level 3 (IV)	Biological: ALD403; Other Names: Eptinezumab-jjmr; Vyepti
Experimental: ALD403 Dose Level 4; ALD403 Dose Level 4 (IV)	Biological: ALD403; Other Names: Eptinezumab-jjmr; Vyepti
Placebo Comparator: Placebo; Placebo (IV)	Biological: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Weeks 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	Weeks 1-12
100% Headache Responder Rate	Participants with an average reduction in headache days of at least 100% over Weeks 1 to 12, as compared with baseline	Weeks 1-12
100% Migraine Responder Rate	Participants with an average reduction in migraine days of at least 100% over Weeks 1 to 12, as compared with baseline	Weeks 1-12
The Change From Baseline in Monthly Headache Days, Weeks 1-12	Monthly headache days, as measured by eDiary. 4-weekly intervals averaged across weeks 1-12.	Weeks 1-12
The Change From Baseline in Monthly Migraine Days, Weeks 1-12	Monthly migraine days, as measured by eDiary. 4-weekly intervals averaged across weeks 1-12.	Weeks 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	Weeks 1-12
Change From Baseline in Percentage of Severe Headaches	The change from baseline in percentage of headaches that are classified as severe over Weeks 9-12	Weeks 9-12
The Change From Baseline to Week 12 in HIT-6 Total 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). A score of 60 or above is labeled as "severe".	Baseline to 12
Percent Change From Baseline in Headache Days	Monthly headache days, as measured by eDiary. 4-weekly intervals averaged across weeks 1-12.	Weeks 1-12
Percent Change From Baseline in Migraine Days	Monthly migraine days, as measured by eDiary. 4-weekly intervals averaged across weeks 1-12.	Weeks 1-12
Time to First Migraine After Dosing	The median number of days after dosing a participant had the next migraine using the eDiary as the recall method	Baseline to Week 49 (End of Study)
Change From Baseline in Monthly Migraine Attacks, Weeks 1-12	The number of monthly migraine attacks summarized over Weeks 1-12. A migraine attack is defined as 1 continuously recorded migraine. One attack may result in multiple migraine days	Weeks 1-12
Change From Baseline in Monthly Headache Episodes, Weeks 1-12	The number of monthly headache episodes as summarized over Weeks 1-12. A headache episode is defined as 1 continuously recorded headache. One episode may result in multiple headache days	Weeks 1-12
Change From Baseline in Monthly Migraine Hours, Weeks 1-12	Migraine hours are the sum of the duration of migraines within 4 week intervals, and the average 4 week duration within 12 week intervals.	Weeks 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.	Weeks 1-12
Change From Baseline to Weeks 9-12 in Percentage of Migraines With Use of Acute Medication	The percent of migraines with acute medication usage. Participants with no migraines will be included with a rate of zero.	Weeks 9-12
Change From Baseline to Weeks 9-12 in Percentage of Headaches With Use of Acute Medication	The percent of headaches with acute medication usage. Participants with no headaches will be included with a rate of zero.	Weeks 9-12
Baseline and Change From Baseline in Short Form Health Survey (SF-36, Version 2.0) at Week 12	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 (range: 0=worst to 100=best). Increases from baseline indicate improvement.	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Alder Biopharmaceuticals, Inc.
• Investigators: Study Director: Jeff TL Smith, MD, Alder Biopharmaceuticals, Inc.

Publications and helpful links

General Publications

• 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.
• 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. Erratum In: J Headache Pain. 2021 May 25;22(1):46.
• Dodick DW, Lipton RB, Silberstein S, Goadsby PJ, Biondi D, Hirman J, Cady R, Smith J. Eptinezumab for prevention of chronic migraine: A randomized phase 2b clinical trial. Cephalalgia. 2019 Aug;39(9):1075-1085. doi: 10.1177/0333102419858355. Epub 2019 Jun 24.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: October 20, 2014
• First Submitted That Met QC Criteria: October 24, 2014
• First Posted (Estimate): October 27, 2014

Study Record Updates

• Last Update Posted (Actual): April 8, 2020
• Last Update Submitted That Met QC Criteria: March 30, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Migraine Disorders; ALD403
• 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-005