A Multicenter Assessment of ALD403 in Frequent Episodic Migraine

Phase 3

Completed

Conditions: Migraine Disorders

Interventions: Drug: ALD403
Drug: Placebo

Registration Number: NCT02559895

Lead Sponsor: Alder Biopharmaceuticals, Inc.

Brief Summary: The purpose of this study is to assess ALD403 in the prevention of migraine headache in frequent episodic migraineurs.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 898

Inclusion Criteria

Diagnosis of migraine at ≤ 50 years of age (ICHD-II, 2004 Section 1)
History of migraine ≥ 12 months with
- ≤ 14 headache days of which at least 4 have to be migraine days (migraine days count as headache days) in each 28 day period in the 3 months prior to screening
- During the 28 days following the screening visit, the subject experiences ≤ 14 headache days of which at least 4 have to be migraine days (migraine days count as headache days) as recorded in the eDiary
No use of any botulinum toxin for migraine or for any other medical/cosmetic reasons requiring injections in the head, face, or neck 4 months prior to screening and during the 28 day period prior to randomization
Headache eDiary was completed on at least 25 of the 28 days prior to randomization

Exclusion Criteria

Confounding pain syndromes, e.g. fibromyalgia, 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- II, 2004 Section 1), 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
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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ALD403 Dose Level 2	ALD403	ALD403 Dose Level 2 (IV)
Placebo	Placebo	Placebo (IV)
ALD403 Dose Level 1	ALD403	ALD403 Dose Level 1 (IV)
ALD403 Dose Level 3	ALD403	ALD403 Dose Level 3 (IV)

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Monthly Migraine Days (Weeks 1-12)	Week 1-12	Monthly migraine days are summarized in 28-day intervals, and averaged across Weeks 1-12

Secondary Outcome Measures

Name	Time	Method
Percent of Migraines With Severe Intensity	Week 1-12	Summary of percent of migraines with severe intensity over Week 1-12.
75% Migraine Responder Rate	Week 1-4	Participants with an average reduction in migraine days of at least 75% over Weeks 1 to 4, as compared with baseline.
Percentage of Participants With a Migraine on the Day After Dosing	1 day	The percentage of participants with a migraine on the day after dosing, where Day 0 is treatment day and Day 1 is the day after dosing
50% Headache Responder Rate	Week 1-12	Participants with an average reduction in headache days of at least 50% over Weeks 1 to 12, as compared with baseline.
100% Migraine Responder Rate	Week 1-12	Participants with a reduction in migraine days of 100% over Weeks 1 to 12, as compared with baseline
100% Headache Responder Rate	Week 1-12	Participants with a reduction in headache days of 100% over Weeks 1 to 12, as compared with baseline.
Change From Baseline in Average Daily Migraine Prevalence to Week 4	Baseline to Week 4	The change in the percentage of days where a participant has a migraine from baseline to Week 4.
Percent of Headaches With Severe Intensity	Week 1-12	Summary of percent of headaches with severe intensity over Weeks 1-12.
50% Migraine Responder Rate	Week 1-12	Participants with an average reduction in migraine days of at least 50% over Weeks 1 to 12, as compared with baseline
75% Headache Responder Rate	Week 1-12	Participants with an average reduction in headache days of at least 75% over Weeks 1 to 12, as compared with baseline.
Change From Baseline in Acute Migraine Medication Days (Weeks 1-12)	Week 1-12	The change in number of days with any triptan or ergotamine use as recorded in the eDiary.
Change From Baseline to Week 12 in Percentage of Migraines With Use of Acute Medication	Week 1-12	The percentage of migraines with acute medication usage. Participants with no migraines will be included with a rate of zero.
Change From Baseline to Week 12 in Percentage of Headaches With Use of Acute Medication	Week 1-12	The percentage of headaches with acute medication usage. Participants with no headaches will be included with a rate of zero.
Change From Baseline in Monthly Headache Days (Weeks 1-12)	Week 1-12	Monthly headache days are summarized in 28-day intervals, and averaged across Weeks 1-12.
Health Related Quality of Life (EQ-5D-5L) at Week 12	Week 12	The EQ-5D-5L is a descriptive system of health-related quality of life states consisting of 5 dimension/questions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which can take one of five responses. The responses record five levels of severity (no problems/slight problems/moderate problems/severe problems/extreme problems) within a particular EQ-5D dimension.
Change From Baseline in Monthly Migraine Hours (Weeks 1-12)	Week 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	Week 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 of Short Form Health Survey (SF-36 v 2.0) Scale Scores	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. All scales are on a range of 0 to 100, with 0 being the worst and 100 being the best. Scales are reported separately. Increases from baseline indicate improvement.
Change in Baseline of Allodynia Symptom Checklist-12 (ASC-12) Total Score	Baseline to Week 12	The ASC-12 includes 12 questions about the frequency of various allodynia symptoms in association with headache attacks. For individuals with more than one type of headache, questions are directed to the "most severe type of headache." Each item is measured in a Likert type scale option with response categories: "Does not apply to me", "never", "rarely", "less than half the time", and "half the time or more". ASC items were scored as 0 (i.e., never, rarely or does not apply to me), 1 (less than half the time), and 2 (half the time or more), yielding scores that ranged from 0 to 24. If a single item is missing, it is scored as a 0. If more than one item is missing the total score will be missing. The interpretation of the total score is, 0-2: none; 3-5: mild; 6-8: moderate; greater than or equal to 9: severe.