A Multicenter Assessment of ALD403 in Frequent Episodic Migraine

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

Official Title
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A Parallel Group, Double-Blind, Randomized, Placebo Controlled, Trial to Evaluate the Efficacy and Safety of ALD403 Administered Intravenously in Patients With Frequent Episodic Migraines

Conditions
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Migraine Disorders

Intervention / Treatment
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* Drug: ALD403
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALD403 Dose Level 1<br>ALD403 Dose Level 1 (IV) | Drug: ALD403<br> <br> * Other names: Vyepti;|
| Experimental: ALD403 Dose Level 2<br>ALD403 Dose Level 2 (IV) | Drug: ALD403<br> <br> * Other names: Vyepti;|
| Experimental: ALD403 Dose Level 3<br>ALD403 Dose Level 3 (IV) | Drug: ALD403<br> <br> * Other names: Vyepti;|
| Placebo Comparator: Placebo<br>Placebo (IV) | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Monthly Migraine Days (Weeks 1-12) | Monthly migraine days are summarized in 28-day intervals, and averaged across Weeks 1-12 | Week 1-12 | 

Secondary 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. | Week 1-12 | 
| 75% Migraine Responder Rate | Participants with an average reduction in migraine days of at least 75% over Weeks 1 to 4, as compared with baseline. | Week 1-4 | 
| 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 | Week 1-12 | 
| Percentage of Participants With a Migraine on the Day After Dosing | 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 | 1 day | 
| 75% Headache Responder Rate | Participants with an average reduction in headache days of at least 75% over Weeks 1 to 12, as compared with baseline. | Week 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. | Week 1-12 | 
| 100% Migraine Responder Rate | Participants with a reduction in migraine days of 100% over Weeks 1 to 12, as compared with baseline | Week 1-12 | 
| 100% Headache Responder Rate | Participants with a reduction in headache days of 100% over Weeks 1 to 12, as compared with baseline. | Week 1-12 | 
| Change From Baseline in Acute Migraine Medication Days (Weeks 1-12) | The change in number of days with any triptan or ergotamine use as recorded in the eDiary. | Week 1-12 | 
| Change From Baseline in Average Daily Migraine Prevalence to Week 4 | The change in the percentage of days where a participant has a migraine from baseline to Week 4. | Baseline to Week 4 | 
| Change From Baseline to Week 12 in Percentage of Migraines With Use of Acute Medication | The percentage of migraines with acute medication usage. Participants with no migraines will be included with a rate of zero. | Week 1-12 | 
| Change From Baseline to Week 12 in Percentage of Headaches With Use of Acute Medication | The percentage of headaches with acute medication usage. Participants with no headaches will be included with a rate of zero. | Week 1-12 | 
| Change From Baseline in Monthly Headache Days (Weeks 1-12) | Monthly headache days are summarized in 28-day intervals, and averaged across Weeks 1-12. | Week 1-12 | 
| Percent of Headaches With Severe Intensity | Summary of percent of headaches with severe intensity over Weeks 1-12. | Week 1-12 | 
| Percent of Migraines With Severe Intensity | Summary of percent of migraines with severe intensity over Week 1-12. | Week 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. | Week 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. | Week 1-12 | 
| Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores | 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. | Baseline to Week 12 | 
| Health Related Quality of Life (EQ-5D-5L) at 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. | Week 12 | 
| Change in Baseline of Allodynia Symptom Checklist-12 (ASC-12) Total Score | 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. | Baseline to Week 12 |