A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients with Chronic Migraine - the REGAIN Study

Study 15Q-MC-CGAI (CGAI; REGAIN) will enable a comprehensive clinical
assessment of two doses of LY2951742 in a patient population for which the
medical need is substantial. This study, along with 2 studies in patients with
episodic migraine, is part of a Phase 3 clinical program that is intended to
provide pivotal efficacy data to support a registration in patients with
migraine.

Primary
To test the hypothesis that at least 1 dose of LY2951742 (120 mg or 240
mg/month) is superior to placebo in the prevention of migraine headache in
patients with chronic migraine

Key Secondary Objectives
If LY2951742 (120 or 240 mg/month) is statistically significantly superior to
placebo on the primary objective, the following key secondary objectives will
be tested with adjustment for multiplicity (only the key secondary objectives
are listed below):
- To compare LY2951742 with placebo with respect to 50% response rate
- To compare LY2951742 with placebo with respect to 75% response rate
-To compare LY2951742 with placebo with respect to 100% response rate
-To compare LY2951742 with placebo with respect to change in functioning
-To compare LY2951742 with placebo with respect to change in use of acute
(abortive) migraine treatment
-To compare LY2951742 with placebo with respect to change in global severity of
the migraine condition

A multisite, randomized, double-blind, parallel, placebo-controlled trial with
5 study periods in patients who meet International Classification of Headache
Disorders (ICHD) criteria for a diagnosis of chronic migraine as confirmed
during a prospective baseline period.

Three treatment arms: LY2951742 (120 mg/month [administered as 1 injection]
with a 240 mg loading dose), LY2951742 (240 mg/month, administered as 2
injections of 120 mg), and placebo. Following a prospective baseline period (30
to 40 days), eligible patients will be randomized in a 2:1:1 ratio to receive
placebo, 120 mg/month of LY2951742, or 240 mg/month of LY2951742, respectively,
and will begin a 3-month double-blind treatment phase. Patients who complete
the double-blind period may enter a 9-month open-label extension phase for
treatment with LY2951742. All patients entering the open-label period will
receive an initial dose of 240 mg of LY2951742 at the first open-label visit.
At the second open-label visit, all patients will receive a 120 mg dose of
LY295174; dosing at subsequent visits will be flexible (either 120 mg or 240
mg/month) at the discretion of the investigator. All patients will also be
followed for a 4-month, post-treatment phase during which patients will no
longer receive any study medication.

The study drug is accompanied by certain risks. The most commonly observed
adverse events in studies in migraine patients were pain at the site of
injection and infection of the upper breathing system, such as bronchitis,
cold, or cold-like symptoms. More information about the known and expected
benefits, risks, serious adverse events (SAEs) and reasonably anticipated
adverse events (AEs) of LY2951742 are to be found in the Investigator*s
Brochure (IB). The studyprocedures, including blood draws, also have certain
risks. The study drug, the study procedures and the combination may also have
other, unknown risks. The risks are described in the subject information sheet.
This current study is being carried out in a patient population for which the
drug already has shown preliminary evidence of efficacy and safety. In
addition, this patient population is experiencing very frequent headaches
leading to a high degree of disability, so treatment options are much needed.