A Multicenter Assessment of ALD403 in Chronic Migraine

• ClinicalTrials.gov Identifier: NCT02275117
• Recruitment Status: Completed
• First Posted: October 27, 2014
• Results First Posted: March 30, 2020
• Last Update Posted: April 8, 2020
• Sponsor: Alder Biopharmaceuticals, Inc.
• Information provided by (Responsible Party): Alder Biopharmaceuticals, Inc.

Tracking Information

• First Submitted Date: October 20, 2014
• First Posted Date: October 27, 2014
• Results First Submitted Date: March 16, 2020
• Results First Posted Date: March 30, 2020
• Last Update Posted Date: April 8, 2020
• Study Start Date: October 2014
• Actual Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 16, 2020)

75% Migraine Responder Rate [ Time Frame: 12 Weeks ]

Participants with an average reduction in migraine days of at least 75% over Weeks 1 to 12, as compared with baseline.

• Original Primary Outcome Measures (submitted: October 24, 2014): Change in migraine days from baseline to week 12. [ Time Frame: 12 weeks ]

Current Secondary Outcome Measures (submitted: March 16, 2020)

• 50% Migraine Responder Rate [ Time Frame: Weeks 1-12 ]
  Participants with an average reduction in migraine days of at least 50% over Weeks 1 to 12, as compared with baseline
• 50% Headache Responder Rate [ Time Frame: Weeks 1-12 ]
  Participants with an average reduction in headache days of at least 50% over Weeks 1 to 12, as compared with baseline
• 100% Headache Responder Rate [ Time Frame: Weeks 1-12 ]
  Participants with an average reduction in headache days of at least 100% over Weeks 1 to 12, as compared with baseline
• 100% Migraine Responder Rate [ Time Frame: Weeks 1-12 ]
  Participants with an average reduction in migraine days of at least 100% over Weeks 1 to 12, as compared with baseline
• The Change From Baseline in Monthly Headache Days, Weeks 1-12 [ Time Frame: Weeks 1-12 ]
  Monthly headache days, as measured by eDiary. 4-weekly intervals averaged across weeks 1-12.
• The Change From Baseline in Monthly Migraine Days, Weeks 1-12 [ Time Frame: Weeks 1-12 ]
  Monthly migraine days, as measured by eDiary. 4-weekly intervals averaged across weeks 1-12.
• Change From Baseline in Percentage of Severe Migraines [ Time Frame: Weeks 1-12 ]
  The change from baseline in percentage of migraines that are classified as severe over Weeks 1-12
• Change From Baseline in Percentage of Severe Headaches [ Time Frame: Weeks 9-12 ]
  The change from baseline in percentage of headaches that are classified as severe over Weeks 9-12
• The Change From Baseline to Week 12 in HIT-6 Total Score [ Time Frame: Baseline to 12 ]
  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".
• Percent Change From Baseline in Headache Days [ Time Frame: Weeks 1-12 ]
  Monthly headache days, as measured by eDiary. 4-weekly intervals averaged across weeks 1-12.
• Percent Change From Baseline in Migraine Days [ Time Frame: Weeks 1-12 ]
  Monthly migraine days, as measured by eDiary. 4-weekly intervals averaged across weeks 1-12.
• Time to First Migraine After Dosing [ Time Frame: Baseline to Week 49 (End of Study) ]
  The median number of days after dosing a participant had the next migraine using the eDiary as the recall method
• Change From Baseline in Monthly Migraine Attacks, Weeks 1-12 [ Time Frame: 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
• Change From Baseline in Monthly Headache Episodes, Weeks 1-12 [ Time Frame: 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
• Change From Baseline in Monthly Migraine Hours, Weeks 1-12 [ Time Frame: 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.
• Change From Baseline in Monthly Headache Hours, Weeks 1-12 [ Time Frame: 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.
• Change From Baseline to Weeks 9-12 in Percentage of Migraines With Use of Acute Medication [ Time Frame: Weeks 9-12 ]
  The percent of migraines with acute medication usage. Participants with no migraines will be included with a rate of zero.
• Change From Baseline to Weeks 9-12 in Percentage of Headaches With Use of Acute Medication [ Time Frame: Weeks 9-12 ]
  The percent of headaches with acute medication usage. Participants with no headaches will be included with a rate of zero.
• Baseline and Change From Baseline in Short Form Health Survey (SF-36, Version 2.0) at Week 12 [ Time Frame: Baseline to 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.

Original Secondary Outcome Measures (submitted: October 24, 2014)

• Evaluate safety of ALD403: laboratory variables, ECG and adverse events [ Time Frame: 49 weeks ]
• Cmax - Peak plasma concentration of ALD403 [ Time Frame: 49 weeks ]
• Tmax - Time to achieve peak plasma concentration of ALD403 [ Time Frame: 49 weeks ]
• AUC - Area under the plasma concentration vs.time curve of ALD403 [ Time Frame: 49 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Multicenter Assessment of ALD403 in Chronic Migraine
• Official Title: 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
• Brief Summary: The purpose of this study is to assess ALD403 in the prevention of migraine headache in chronic migraineurs.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Migraine Disorders

Intervention

• Biological: ALD403
  Other Names:

  • Eptinezumab-jjmr
  • Vyepti
• Biological: Placebo

Study Arms

• Experimental: ALD403 Dose Level 1
  ALD403 Dose Level 1 (IV)
  Intervention: Biological: ALD403
• Experimental: ALD403 Dose Level 2
  ALD403 Dose Level 2 (IV)
  Intervention: Biological: ALD403
• Experimental: ALD403 Dose Level 3
  ALD403 Dose Level 3 (IV)
  Intervention: Biological: ALD403
• Experimental: ALD403 Dose Level 4
  ALD403 Dose Level 4 (IV)
  Intervention: Biological: ALD403
• Placebo Comparator: Placebo
  Placebo (IV)
  Intervention: Biological: Placebo

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 16, 2020): 665
• Original Estimated Enrollment (submitted: October 24, 2014): 600
• Actual Study Completion Date: November 2016
• Actual Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Georgia, New Zealand, United States

Administrative Information

• NCT Number: NCT02275117
• Other Study ID Numbers: ALD403-CLIN-005
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Alder Biopharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Alder Biopharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Alder Biopharmaceuticals, Inc.
• Verification Date: March 2020