A Multicenter Assessment of LBR-101 in High Frequency Episodic Migraine

Study Overview
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Brief Summary
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The purpose of this study is to determine whether monthly subcutaneous administration of LBR-101 (fremanezumab) is safe and provides migraine prevention in subjects with high frequency episodic migraine.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Study Comparing the Efficacy and Safety of Two Doses of Subcutaneous LBR-101 With Placebo for the Preventive Treatment of High Frequency Episodic Migraine

Conditions
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Episodic Migraine Headache

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. Subjects fulfilling criteria for episodic migraine as per the Second Edition of The International Headache Society (Olesen and Steiner 2004), who experience migraine at high frequency as follows: i. History of headaches on more than 8 days per month for at least 3 months prior to screening ii. Verification of headache frequency through prospectively collected baseline information during the 28-day run-in phase demonstrating headaches (of any type) on at least 8 days with at total of 8 to 14 days* fulfilling criteria for migraine. *Operational definition for migraine and probable migraine days are presented in the statistical section of this protocol. 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 by entry of headache data on a minimum of 22/28 days (80% compliance). Exclusion Criteria: 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 six months prior to screening. Subject uses 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: Treatment
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 High Dose 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 Low Dose 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 Monthly Migraine Days During the 28-day Post Treatment Period Ending With Week 12 | A migraine day was endorsed when at least 1 of the following situations occurred: 1) A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache endorsing criteria for migraine, or 2) a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache endorsing criteria for probable migraine, a migraine subtype where only one migraine criterion is missing, or 3) the participant used acute migraine medication (triptans and ergot compounds) to treat a headache of any duration, or 4) any of the above days preceded or followed by a day with a headache of any duration. This calculation was defined as the change from baseline in the number of headache days 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 | 
| Number of Participants Reporting Mild, Moderate, and Severe Adverse Events (AEs) | Adverse events were rated based on the investigator's clinical judgment. Mild: awareness of a sign or symptom that was easily tolerated Moderate: sign or symptom intense enough to interfere with usual activity Severe: interfered significantly with ability to do work or usual activity | Up to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Number of Days With Headache of Any Severity | 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 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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High Frequency Episodic Migraine Headache, Episodic Migraine Headache, Migraine Headache