A phase 3, randomised, placebo-controlled study of erenumab for the prevention of chronic migraine in patients from Asia: the DRAGON study

Abstract

Abstact: BACKGROUND: DRAGON was a phase 3, randomised, double-blind, placebo-controlled study which evaluated the efficacy and safety of erenumab in patients with chronic migraine (CM) from Asia not adequately represented in the global pivotal CM study.

Methods: DRAGON study was conducted across 9 Asian countries or regions including mainland China, India, the Republic of Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Patients (N = 557) with CM (aged 18-65 years) were randomised (1:1) to receive once-monthly subcutaneous erenumab 70 mg or matching placebo for 12 weeks. The primary endpoint was the change in monthly migraine days (MMD) from baseline to the last 4 weeks of the 12-week double-blind treatment phase (DBTP). Secondary endpoints included achievement of ≥ 50% reduction in MMD, change in monthly acute headache medication days, modified migraine disability assessment (mMIDAS), and safety. Study was powered for the primary endpoint of change from baseline in MMD.

Results: At baseline, the mean (SD) age was 41.7 (± 10.9) years, and 81.5% (n = 454) patients were women. The mean migraine duration was 18.0 (± 11.6) years, and the mean MMD was 19.2 (± 5.4). 97.8% (n = 545) randomised patients completed the DBTP. Overall, demographics and baseline characteristics were balanced between the erenumab and placebo groups except for a slightly higher proportion of women in the placebo group. At Week 12, the adjusted mean change from baseline in MMD was - 8.2 days for erenumab and - 6.6 days for placebo, with a statistically significant difference for erenumab versus placebo (adjusted mean difference vs placebo: - 1.57 [95%CI: - 2.83, - 0.30]; P = 0.015). A greater proportion of patients treated with erenumab achieved ≥ 50% reduction in MMD versus placebo (47.0% vs 36.7%, P = 0.014). At Week 12, greater reductions in monthly acute headache medication days (- 5.34 vs - 4.66) and mMIDAS scores (- 14.67 vs - 12.93) were observed in patients treated with erenumab versus placebo. Safety and tolerability profile of erenumab was comparable to placebo, except the incidence of constipation (8.6% for erenumab vs 3.2% for placebo).

Conclusion: DRAGON study demonstrated the efficacy and safety of erenumab 70 mg in patients with CM from Asia. No new safety signals were observed during the DBTP compared with the previous trials.

Trial registration: NCT03867201.

Keywords: Asian; Calcitonin gene-related peptide; Chronic migraine; Clinical trial; Efficacy; Erenumab; Monoclonal antibodies; Safety.

Fig. 1

a Study design. Note: For patients not entering the OLTP, the safety follow-up visit occurred 12 weeks after the last dose of the DBTP. In the selected countries or regions, patients completing the DBTP on the study drug were eligible to participate in the OLTP (until launch of erenumab in the respective country or region). The study was powered only for the primary endpoint assessed in the overall population with an alpha level of 0.05. The endpoints were assessed as change from baseline over the last 4 weeks of the DBTP. * Duration of baseline was up to 35 days (5 weeks) due to COVID-19, with the last 28 days of this period considered for the assessment of headache frequency (MMD). DBTP, double-blind treatment phase; OLTP, open-label treatment phase; QM, once monthly; SC, subcutaneous. b Patient disposition in the DBTP. Note: *A patient is defined as a completer for the DBT if the individual had received the Week 8 dose (erenumab or placebo). ^† A patient is defined as completer for the DBTP, if the individual had completed all scheduled visits in the DBTP, including Week 12 visit, or entered in the OLTP. For patients who continued to OLTP, the cut-off was end of treatment. For patients who entered into the safety follow-up after double-blind treatment, the cut-off is 11-Aug-2021 or end of study whichever is the earliest. Screened were those patients who had signed an informed consent form. Full analysis set comprised all randomised patients. DBT, double-blind treatment; DBTP, double-blind treatment phase; OLTP, open-label treatment phase

Fig. 2

Change from baseline in MMD by treatment and visit (Full analysis set). Adjusted LSM and 95% CIs from the primary analysis model are presented. Note: The primary efficacy endpoint (change from baseline in MMD) was analysed using a generalised linear mixed effects repeated measures model based on observed monthly data during the treatment period. CI, confidence interval; LSM, least-squares means; MMD, monthly migraine days

Fig. 3

Proportion of patients achieving ≥ 50% reduction from baseline in MMD (Full Analysis Set). P-values reported for the dichotomous secondary endpoint (proportion of patients achieving ≥ 50% reduction in MMD) are nominal and should be interpreted with caution. n, number of patients who achieved ≥ 50% reduction in MMD; M, total number of patients in the treatment group with response variable defined. Note: Statistical analysis for the proportion of patients with ≥ 50% reduction from baseline in MMD was done using CMH test adjusting for stratification factor after missing data was imputed (NRI). CI, confidence interval; CMH Cochran–Mantel–Haenszel; MMD monthly migraine day; NRI non-responder imputation; OR, odds ratio