Table 1.
Summary of EVOLVE-1, EVOLVE-2, REGAIN, and CONQUER trials
| Study title and identifiers | EM or CM | Key design characteristics | Primary outcome | Summary of results |
|---|---|---|---|---|
| A Phase 3, Randomized, Double-blind, Placebo-controlled Study of LY2951742 in Patients with EM (EVOLVE-1) NCT02614183 [19] | EM | Adults aged 18–65 years with at least a 1-year history of migraine. Patients received subcutaneous injection treatments once monthly for 6 months and were followed-up for 5 months after last injection. Patients were randomized 2:1:1 to receive placebo or monthly subcutaneous galcanezumab 120 mg or galcanezumab 240 mg | Overall mean change from baseline in the number of monthly migraine headache days during the treatment period |
Enrolled: 862 Study start date: 11/2015 Study completion date: 3/2017 Primary outcome met for both galcanezumab doses (p < 0.001) Treatment with galcanezumab significantly reduced monthly migraine headache days (both p < 0.001) by 4.7 days (120 mg) and 4.6 days (240 mg) compared with placebo (2.8 days). All key secondary measures (reduction in monthly migraine headache days, migraine headache days with acute medication use, and scores from the Migraine-Specific Quality of Life questionnaire, Patient Global Impression of Severity, MIDAS) were also significant after multiplicity adjustment. There were no meaningful differences between 120-mg and 240-mg doses of galcanezumab on measures of efficacy |
|
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients With EM (EVOLVE-2) |
EM | Adults aged 18–65 years with a diagnosis of migraine with or without aura, and at least a 1-year history of migraine. Patients received subcutaneous injection treatments once monthly for 6 months and were followed up for 4 months after last injection. Patients were randomized 2:1:1 to receive placebo, galcanezumab 120 mg, or galcanezumab 240 mg | Overall mean change from baseline in monthly migraine headache days |
Enrolled: 922 Study start date: 12/2015 Study completion date: 3/2017 Primary outcome met for both galcanezumab doses (p < 0.001) Mean monthly migraine headache days were reduced by 4.3 and 4.2 days for galcanezumab 120 and 240 mg, respectively, and 2.3 days for placebo. The group differences (95% CIs) versus placebo were 2.0 (− 2.6, − 1.5) and 1.9 (− 2.4, − 1.4), respectively. Both doses were superior to placebo for all key secondary endpoints (≥ 50%, ≥ 75%, 100% response rates; monthly migraine headache days with acute migraine medication use; Patient Global Impression of Severity rating; the Role Function-Restrictive score of the Migraine-Specific Quality of Life Questionnaire). Injection site pain was the most common treatment-emergent AE, reported at similar rates in all treatment groups. Both galcanezumab doses had significantly more injection site reactions and injection site pruritus, and the 240-mg group had significantly more injection site erythema versus placebo |
|
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients With CM (REGAIN) |
CM | Adults aged 18–65 years, with a diagnosis of CM as defined by the International Classification of Headache Disorders, 3rd edn, beta version (ICHD-3 beta) guidelines and migraine onset before 50 years of age. Patients received subcutaneous injection treatments once monthly for 6 months (3 months double-blind, placebo-controlled treatment, and 3 months open-label treatment). Patients received subcutaneous injection treatments once monthly for 12 months (3 months double-blind, placebo-controlled treatment, and 9 months open-label treatment), and were followed up for 4 months posttreatment. Patients were randomized 2:1:1 to receive placebo, galcanezumab 120 mg, or galcanezumab 240 mg | The overall mean change from baseline in the number of monthly migraine headache days during the 3-month double-blind treatment phase |
Enrolled: 1117 Study start date: 11/2015 Study completion date: 3/2017 Primary outcome met for both galcanezumab doses (p < 0.001) Mean number of monthly headache days at baseline was 19.4 for the total sample. Both galcanezumab dose groups demonstrated greater overall mean reduction in the number of monthly migraine headache days compared to placebo (placebo − 2.7, galcanezumab 120 mg − 4.8, galcanezumab 240 mg − 4.6). There were no clinically meaningful differences between galcanezumab doses and placebo on any safety or tolerability outcome except for a higher incidence of treatment-emergent injection-site reaction (p < 0.01), injection-site erythema (p < 0.001), injection-site pruritus (p < 0.01), and sinusitis (p < 0.05) in the galcanezumab 240-mg group relative to placebo |
|
A Randomized, Double-Blind, Placebo-Controlled Study of Galcanezumab in Adults With Treatment-Resistant Migraine (CONQUER) |
EM or CM | Adults aged 18–75 years, with EM (58%) or CM (42%), with migraine onset before the age of 50 years, who had a documented failure of preventive medications from two to four drug treatments in the past 10 years owing to lack of efficacy or tolerability, or both. Patients received subcutaneous injection treatments once monthly for 6 months (3 months double-blind, placebo-controlled treatment, and 3 months open-label treatment). Patients were randomized 1:1 to receive placebo or galcanezumab 120 mg (with a loading dose of 240 mg) | Overall mean change from baseline in number of monthly migraine headache days during the 3-month treatment period in all patients who were randomly assigned and received at least one dose of study drug |
Enrolled: 462 Study start date: 7/2018 Study completion date: 6/2019 Primary outcome met for 120-mg galcanezumab dose (p < 0.0001) Galcanezumab-treated patients had significantly greater reduction in migraine headache days versus placebo across months 1–3. The galcanezumab group had on average 4·1 fewer monthly migraine headache days compared with baseline (13·4), while the placebo group had on average 1·0 fewer than at baseline (13·0; between-group difference − 3·1 [95% CI − 3·9 to − 2·3]; p < 0·0001; effect size = 0·72). Types and number of treatment-emergent AEs were similar between galcanezumab and placebo. Treatment-emergent AEs were reported in 122 (53%) of 230 patients in the placebo group and 119 (51%) of 232 patients in the galcanezumab group. There were 4 serious AEs during the study, 2 (1%) reported in the placebo group and 2 (1%) reported in the galcanezumab group |
AE adverse event, CM chronic migraine, EM episodic migraine, MIDAS Migraine Disability Assessment