Assessment of LBR-101 In Chronic Migraine

Study Overview
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Brief Summary
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The purpose of the study is to determine whether monthly subcutaneous administration of LBR-101 (fremanezumab) is safe and provides migraine prevention in patients with chronic migraine.

Detailed Description
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Two distinct doses of subcutaneous LBR-101 (fremanezumab) administered monthly will be compared to placebo for safety and efficacy. The mean change from baseline in the number of cumulative headache hours measured at the 28-day period ending with week 12.

Official Title
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A Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel Group, Multi-dose Study Comparing the Efficacy and Safety of Subcutaneous LBR-101 With Placebo for the Preventive Treatment of Chronic Migraine

Conditions
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Chronic Migraine

Intervention / Treatment
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* Drug: LBR-101 High Dose
* Drug: LBR-101 Low Dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged 18 to 65 years of age. A signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study including any known and potential risks and available alternative treatments. Chronic migraine meeting the diagnostic criteria listed in the International Classification of Headache Disorders (ICHD-III beta version, 2013) Body Mass Index (BMI) of 17.5 to 37.5 kg/m2, and a total body weight between 50 kg and 120 kg inclusive. Demonstrated compliance with the electronic headache diary during the run-in period headache data on a minimum of 22/28 days (80% diary compliance) Exclusion Criteria: Onset of chronic migraine after the age of 50 years. Subject has received onabotulinum toxin A for migraine or for any medical or cosmetic reasons requiring injections in the head, face, or neck during the 6 months prior to study entry. Subject is using medications containing opioids (including codeine) or barbiturates (including Fiorinal®, Fioricet®, or any other combination containing butalbital) on more than 4 days per month for the treatment of migraine or for any other reason. Failed > 2 medication categories or > 3 preventive medications (within two medication categories) due to lack of efficacy for prophylactic treatment of episodic or chronic migraine after an adequate therapeutic trial Treatment with an investigational drug or device within 30 days of study entry or any prior exposure to a monoclonal antibody targeting the CGRP pathway.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LBR-101 High Dose<br>Subcutaneous High Dose LBR-101 Administered Monthly x 3 | Drug: LBR-101 High Dose<br>* Subcutaneously Administered LBR-101 Monthly x 3<br>* Other names: Fremanezumab;|
| Experimental: LBR-101 Low Dose<br>Subcutaneous Low Dose LBR-101 Administered Monthly x 3 | Drug: LBR-101 Low Dose<br>* Subcutaneously Administered LBR-101 Monthly x 3<br>* Other names: Fremanezumab;|
| Placebo Comparator: Placebo<br>Subcutaneous Placebo Administered Monthly x 3 | Drug: Placebo<br>* Subcutaneously Administered Placebo (Vehicle) Monthly x 3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in the Number of Monthly Cumulative Headache Hours of Any Severity on Headache Days Relative to the 28-day Post-treatment Period Ending With Week 12 | A headache day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache of any severity or the participant used acute migraine medication (triptans and ergot compounds) to treat a headache. This calculation was defined as the change from baseline in the number of hours with headache of any severity during the 28-day post treatment period ending at week 12. Headache severity was rated daily by the participant as either no pain, mild, moderate, or severe. | Baseline to week 12 | 
| Number of Participants With at Least One Adverse Event | An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Relationship of AE to treatment was determined by the Investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. | Baseline to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in the Number of Headache Days of at Least Moderate Severity Relative to the 28-day Post-treatment Period Ending With Week 12 | A headache day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache of any severity or the participant used acute migraine medication (triptans and ergot compounds) to treat a headache. This calculation was defined as the change from baseline in the number of headache days of at least moderate severity during the 28-day post treatment period ending at week 12. Headache severity was rated daily by the participant as either no pain, mild, moderate, or severe. | Baseline to week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Headache, Migraine, Chronic Migraine