A Study Evaluating the Effectiveness of AMG 334 Injection in Preventing Migraines in Adults Having Failed Other Therapies

Study Overview
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Brief Summary
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The purpose of this study is to determine if AMG 334 is effective in treating migraines in patients who have failed other preventive migraine treatments.

Detailed Description
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This study was a double blind, placebo-controlled, randomized trial in adult patients with episodic migraine. There was a screening period of 2 weeks to assess initial eligibility, and a 4-week baseline period. After randomization, participants entered the double-blind treatment epoch (DBTE) and had clinic visits for 12 weeks. All participants who completed the DBTE were eligible to enter the Open-Label Treatment Epoch (OLTE) for up to 156 weeks. All participants had a 12 week Follow-Up Epoch and a a Follow-Up visit 16 weeks after the last dose of AMG334 unless the participant continued on commercially available AMG334. Participants who had demonstrated clinical benefit were eligible to enter a Post Trial Access (PTA-Open Label Treatment Epoch) of flexible duration for approximately 6 months.

Official Title
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A 12-week Double-blind, Randomized, Multicenter Study Comparing the Efficacy and Safety of Once Monthly Subcutaneous 140 mg AMG 334 Against Placebo in Adult Episodic Migraine Patients Who Have Failed 2-4 Prophylactic Treatments (LIBERTY)

Conditions
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Episodic Migraine

Intervention / Treatment
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* Biological: AMG334 (70 mg) Pre-Filled Syringe (PFS)
* Biological: Placebo Pre-Filled Syringe (PFS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented history of migraine in the 12 months prior to screen 4-14 days per month of migraine symptoms >=80% diary compliance during the Baseline period Failure of previous migraine prophylactic treatments Exclusion Criteria: >50 years old at migraine onset Pregnant or nursing History of cluster or hemiplegic headache Evidence of seizure or psychiatric disorder Score of over 19 on Beck Depression Inventory-2 Active chronic pain syndrome Cardiac or hepatic disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo DB<br>Matching placebo subcutaneous injections administered every 4 weeks during Double-Blind Epoch | Biological: Placebo Pre-Filled Syringe (PFS)<br>* Subcutaneous injection of matching placebo<br>|
| Experimental: AMG334 140 mg DB<br>AMG334 70 mg subcutaneous injections (2) administered every 4 weeks during Double-Blind Epoch | Biological: AMG334 (70 mg) Pre-Filled Syringe (PFS)<br>* Two injections of AMG 334 70 mg (equaling 140 mg total dose) will be administered via subcutaneous injection<br>|
| Experimental: AMG334 140 mg DB cont on AMG334 140 mg<br>AMG334 70 mg subcutaneous injections (2) during DB continued on AMG334 140 mg in Open-Label Epoch | Biological: AMG334 (70 mg) Pre-Filled Syringe (PFS)<br>* Two injections of AMG 334 70 mg (equaling 140 mg total dose) will be administered via subcutaneous injection<br>|
| Experimental: Placebo in DB to AMG334 140 mg<br>Placebo in Double-Blind Epoch (DB) switched to AMG334 140 mg in Open-Label Epoch | Biological: AMG334 (70 mg) Pre-Filled Syringe (PFS)<br>* Two injections of AMG 334 70 mg (equaling 140 mg total dose) will be administered via subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With at Least 50% Reduction From Baseline of Monthly Migraine Days (MMD) in the Last Month (Last 4 Weeks of Treatment) | A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as: with/without aura, lasting ≥ 30 minutes with at least 1 criteria: 1. ≥ 2 of following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity, 2. ≥ 1 of the following symptoms: nausea and/or vomiting, photophobia and phonophobia. If a migraine-specific medication (ie, triptan or ergotamine) was taken during aura, or a headache, it was counted as a migraine day regardless of duration and pain features/associated symptoms. | Baseline, Month 3 (last 4 weeks of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Monthly Migraine Days (MMD) in the Last Month (Last 4 Weeks of Treatment) | A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as: with/without aura, lasting ≥ 30 minutes with at least 1 criteria: 1. ≥ 2 of following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity, 2. ≥ 1 of the following symptoms: nausea and/or vomiting, photophobia and phonophobia. If a migraine-specific medication (ie, triptan or ergotamine) was taken during aura, or a headache, it was counted as a migraine day regardless of duration and pain features/associated symptoms. | Baseline, Month 3 (last 4 weeks of treatment) | 
| Change From Baseline in Physical Impairment and Everyday Activities as Measured by the Migraine Physical Function Impact Diary (MPFID) at Month 3 | MPFID has 2 domains: Everyday Activities, which consisted of 7 items and Physical Impairment with 5 items using a 5-point scale. Scores were summed across each domain and were then transformed and used for analyses. Transforming MPFID domain scores ranged from 0-100, where higher scores were indicative of greater migraine impact (ie, higher burden) | Baseline, Month 3 (last 4 weeks of treatment) | 
| Change in the Number of Monthly Acute Migraine-specific Medication Treatment Days at Month 3 | Number of days on which acute migraine-specific medications were used were recorded in eDiary between each monthly IP dose. Migraine-Specific medications included two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications. Monthly migraine-specific medication use at baseline was the number of migraine-specific medication treatment days in the baseline period. | Baseline, Month 3 (last 4 weeks of treatment) | 
| Percentage of Participants With a 75% Reduction From Baseline of Monthly Migraine Days (MMD) in the Last Month (Last 4 Weeks of Treatment) | A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as: with/without aura, lasting ≥ 30 minutes with at least 1 criteria: 1. ≥ 2 of following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity, 2. ≥ 1 of the following symptoms: nausea and/or vomiting, photophobia and phonophobia. If a migraine-specific medication (ie, triptan or ergotamine) was taken during aura, or a headache, it was counted as a migraine day regardless of duration and pain features/associated symptoms. | Baseline, Month 3 (last 4 weeks of treatment) | 
| Percentage of Participants With a 100% Reduction From Baseline of Monthly Migraine Days (MMD) in the Last Month (Last 4 Weeks of Treatment) | A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as: with/without aura, lasting ≥ 30 minutes with at least 1 criteria: 1. ≥ 2 of following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity, 2. ≥ 1 of the following symptoms: nausea and/or vomiting, photophobia and phonophobia. If a migraine-specific medication (ie, triptan or ergotamine) was taken during aura, or a headache, it was counted as a migraine day regardless of duration and pain features/associated symptoms. | Baseline, Month 3 (last 4 weeks of treatment) | 
| Number of Participants Who Developed Anti-AMG334 Antibodies | Blood samples for immunogenicity testing were collected for the measurement of anti-AMG334 binding antibodies. | Baseline up to approximately 180 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine, attack, headache, episodic, aura, AMG 334, CGRP receptor agonist, erenumab, adult