Clinical trial NCT02025556: A Multicenter Assessment of LBR-101 in High Frequency Episodic Migraine
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Episodic Migraine Headache
Keywords: High Frequency Episodic Migraine Headache
Episodic Migraine Headache
Migraine Headache
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
Collaborators: name: NCGS, Inc.
First posted: 2014-01-01
Enrollment: 297
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Mean Change From Baseline in the Monthly Migraine Days During the 28-day Post Treatment Period Ending With Week 12
timeFrame: Baseline to week 12
measure: Number of Participants With at Least One Adverse Event
timeFrame: Baseline to week 12
measure: Number of Participants Reporting Mild, Moderate, and Severe Adverse Events (AEs)
timeFrame: Up to week 12
Secondary outcomes:
measure: Change From Baseline in Number of Days With Headache of Any Severity
timeFrame: Baseline to week 12
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Teva Investigational Site 145
state: Arizona
city: Phoenix
country: United States
facility: Teva Investigational Site 130
state: Arizona
city: Scottsdale
country: United States
facility: Teva Investigational Site 117
state: Arizona
city: Little Rock
country: United States
facility: Teva Investigational Site 158
state: Arkansas
city: Anaheim
country: United States
facility: Teva Investigational Site 161
state: California
city: Fullerton
country: United States
facility: Teva Investigational Site 116
state: California
city: Long Beach
country: United States
facility: Teva Investigational Site 119
state: California
city: Oceanside
country: United States
facility: Teva Investigational Site 146
state: California
city: San Francisco
country: United States
facility: Teva Investigational Site 113
state: California
city: Stanford
country: United States
facility: Teva Investigational Site 108
state: California
city: Walnut Creek
country: United States
facility: Teva Investigational Site 112
state: California
city: Boulder
country: United States
facility: Teva Investigational Site 132
state: Colorado
city: Stamford
country: United States
facility: Teva Investigational Site 162
state: Connecticut
city: DeLand
country: United States
facility: Teva Investigational Site 143
state: Florida
city: Hialeah
country: United States
facility: Teva Investigational Site 137
state: Florida
city: Hollywood
country: United States
facility: Teva Investigational Site 159
state: Florida
city: Jacksonville
country: United States
facility: Teva Investigational Site 101
state: Florida
city: Jacksonville
country: United States
facility: Teva Investigational Site 166
state: Florida
city: Maitland
country: United States
facility: Teva Investigational Site 129
state: Florida
city: Orlando
country: United States
facility: Teva Investigational Site 167
state: Florida
city: Ormond Beach
country: United States
facility: Teva Investigational Site 139
state: Florida
city: Port Orange
country: United States
facility: Teva Investigational Site 140
state: Florida
city: South Miami
country: United States
facility: Teva Investigational Site 160
state: Florida
city: Atlanta
country: United States
facility: Teva Investigational Site 149
state: Georgia
city: Decatur
country: United States
facility: Teva Investigational Site 164
state: Georgia
city: Douglasville
country: United States
facility: Teva Investigational Site 134
state: Georgia
city: Evansville
country: United States
facility: Teva Investigational Site 125
state: Indiana
city: Lenexa
country: United States
facility: Teva Investigational Site 133
state: Kansas
city: Brockton
country: United States
facility: Teva Investigational Site 135
state: Massachusetts
city: New Bedford
country: United States
facility: Teva Investigational Site 124
state: Massachusetts
city: Springfield
country: United States
facility: Teva Investigational Site 151
state: Massachusetts
city: Watertown
country: United States
facility: Teva Investigational Site 109
state: Massachusetts
city: Worcester
country: United States
facility: Teva Investigational Site 115
state: Massachusetts
city: Ann Arbor
country: United States
facility: Teva Investigational Site 110
state: Michigan
city: Kalamazoo
country: United States
facility: Teva Investigational Site 114
state: Michigan
city: Golden Valley
country: United States
facility: Teva Investigational Site 150
state: Minnesota
city: Kansas City
country: United States
facility: Teva Investigational Site 152
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 104
state: Missouri
city: Springfield
country: United States
facility: Teva Investigational Site 107
state: Missouri
city: Reno
country: United States
facility: Teva Investigational Site 148
state: Nevada
city: Bronx
country: United States
facility: Teva Investigational Site 105
state: New York
city: Greensboro
country: United States
facility: Teva Investigational Site 131
state: North Carolina
city: Raleigh
country: United States
facility: Teva Investigational Site 118
state: North Carolina
city: Raleigh
country: United States
facility: Teva Investigational Site 165
state: North Carolina
city: Winston-Salem
country: United States
facility: Teva Investigational Site 168
state: North Carolina
city: Canton
country: United States
facility: Teva Investigational Site 122
state: Ohio
city: Cincinnati
country: United States
facility: Teva Investigational Site 141
state: Ohio
city: Cincinnati
country: United States
facility: Teva Investigational Site 142
state: Ohio
city: Cleveland
country: United States
facility: Teva Investigational Site 155
state: Ohio
city: Columbus
country: United States
facility: Teva Investigational Site 102
state: Ohio
city: Oklahoma City
country: United States
facility: Teva Investigational Site 127
state: Oklahoma
city: Philadelphia
country: United States
facility: Teva Investigational Site 111
state: Pennsylvania
city: Goose Creek
country: United States
facility: Teva Investigational Site 120
state: South Carolina
city: Bristol
country: United States
facility: Teva Investigational Site 153
state: Tennessee
city: Memphis
country: United States
facility: Teva Investigational Site 126
state: Tennessee
city: Nashville
country: United States
facility: Teva Investigational Site 154
state: Tennessee
city: Arlington
country: United States
facility: Teva Investigational Site 128
state: Texas
city: Austin
country: United States
facility: Teva Investigational Site 121
state: Texas
city: Austin
country: United States
facility: Teva Investigational Site 136
state: Texas
city: Mansfield
country: United States
facility: Teva Investigational Site 156
state: Texas
city: Salt Lake City
country: United States
facility: Teva Investigational Site 157
state: Utah
city: Charlottesville
country: United States
facility: Teva Investigational Site 123
state: Virginia
city: Roanoke
country: United States
facility: Teva Investigational Site 144
state: Virginia
Study officials:
affiliation: Teva Pharmaceuticals USA
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References:
citation: Silberstein SD, Rapoport AM, Loupe PS, Aycardi E, McDonald M, Yang R, Bigal ME. The Effect of Beginning Treatment With Fremanezumab on Headache and Associated Symptoms in the Randomized Phase 2 Study of High Frequency Episodic Migraine: Post-Hoc Analyses on the First 3 Weeks of Treatment. Headache. 2019 Mar;59(3):383-393. doi: 10.1111/head.13446. Epub 2018 Nov 18.
citation: VanderPluym J, Dodick DW, Lipton RB, Ma Y, Loupe PS, Bigal ME. Fremanezumab for preventive treatment of migraine: Functional status on headache-free days. Neurology. 2018 Sep 18;91(12):e1152-e1165. doi: 10.1212/01.wnl.0000544321.19316.40. Epub 2018 Aug 17.
citation: Halker Singh RB, Aycardi E, Bigal ME, Loupe PS, McDonald M, Dodick DW. Sustained reductions in migraine days, moderate-to-severe headache days and days with acute medication use for HFEM and CM patients taking fremanezumab: Post-hoc analyses from phase 2 trials. Cephalalgia. 2019 Jan;39(1):52-60. doi: 10.1177/0333102418772585. Epub 2018 May 3.
citation: Cohen JM, Dodick DW, Yang R, Newman LC, Li T, Aycardi E, Bigal ME. Fremanezumab as Add-On Treatment for Patients Treated With Other Migraine Preventive Medicines. Headache. 2017 Oct;57(9):1375-1384. doi: 10.1111/head.13156. Epub 2017 Sep 1.
citation: Bigal ME, Dodick DW, Rapoport AM, Silberstein SD, Ma Y, Yang R, Loupe PS, Burstein R, Newman LC, Lipton RB. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study. Lancet Neurol. 2015 Nov;14(11):1081-90. doi: 10.1016/S1474-4422(15)00249-5. Epub 2015 Sep 30.