Head-to-head Study of Erenumab Against Topiramate in Patients With Episodic and Chronic Migraine

Phase 4

Completed

Conditions: Migraine

Interventions: Biological: Erenumab
Drug: Topiramate
Drug: Topiramate matching placebo
Biological: Erenumab matching placebo

Registration Number: NCT03828539

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: This study used a single-cohort, 2-treatment arm, parallel-group randomized, double-blind, double-dummy design in adult patients with episodic migraine and chronic migraine, who had to be either naïve or not suitable for or could have failed up to three prophylactic treatments out of: propranolol/metoprolol, amitriptyline, flunarizine. Patients were stratified into groups according to their number of migraine days during the baseline period.

Detailed Description: All patients completing the Baseline period and fulfilling baseline eligibility criteria were invited to participate to the Double-blind, double-dummy Treatment Epoch (DBTE, 24 weeks) .

Eligible patients were randomized to one of two treatment arms. DBTE started with a titration phase for topiramate of a maximum of 6 weeks to determine the maximal tolerated dose and aimed to reach the recommended treatment dose of 100 mg according to the German SmPC. After the titration phase, maintenance phase started (18 weeks). Topiramate dose had to be maintained until the end of the DBTE. Erenumab dose at beginning of the DBTE was determined patient individually by the investigator based on the guidance provided in the SmPC and was either 70 mg or 140 mg. Dose escalation from 70 mg to 140 mg in case of insufficient response was considered at anytime during the DBTE.

Dose reduction of topiramate and erenumab was not allowed during DBTE (Week 0 to Week 24). After Week 24 or if the patient discontinued study drug, a one week double-blind taper off phase followed to ensure proper down titration for topiramate. At the end of the DBTE (24 weeks) the final assessment occurred to address the objectives.

A Follow-Up Visit 4 weeks after last study visit (or 8 weeks after last IMP injection for discontinued patients) was required as part of routine safety monitoring. The primary analysis was triggered when all patients had completed their respective last visit of the DBTE.

The End of study occurred when the last patient completed last visit (LPLV).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 777

Inclusion Criteria

Documented history of migraine in the 12 months prior to screen
at least 4 days per month of migraine symptoms
>=80% diary compliance during the Baseline period
Patients must be either naïve or not suitable or have failed previous migraine prophylactic treatments

Key

Exclusion Criteria

Older than 50 years of age at migraine onset
Pregnant or nursing
History of cluster or hemiplegic headache
History or evidence of major psychiatric disorder
Score of 19 or higher on Beck Depression Inventory (BDI)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Topiramate	Topiramate matching placebo	Topiramate in the highest tolerated dose (50 - 100 mg/day)
Erenumab	Erenumab	70 mg and 140 mg Erenumab
Erenumab	Erenumab matching placebo	70 mg and 140 mg Erenumab
Topiramate	Topiramate	Topiramate in the highest tolerated dose (50 - 100 mg/day)

Primary Outcome Measures

Name	Time	Method
Proportion of Patients With Treatment Discontinuation Due to an Adverse Event (AE) During the Double-blind Treatment Epoch/Period (DBTE)	24 Weeks	The primary objective was to demonstrate the tolerability of 70 mg and 140 mg erenumab compared to topiramate in the highest tolerated dose assessed by the rate of patients discontinuing treatment due to AE during the double-blind epoch of the study.

Secondary Outcome Measures

Name	Time	Method
Number of Patients With at Least 50% Reduction From Baseline in Monthly Migraine Days (MMD) Over the Last Three Months (Month 4, 5, and 6)	Baseline, Last three months (month 4, 5, and 6)	The secondary objective of this study was to evaluate the effect of erenumab compared to topiramate on the proportion of patients with at least 50% reduction from baseline in MMDs. The Baseline period was defined as the period between Week -4 and the day prior to first dose. This was analyzed by logistic regression over the last 3 months (months 4, 5, and 6) of treatment. All the subjects' data collected regarding 50% response in MMD was used in the analysis regardless of whether subjects discontinue study treatment or not. Subjects with missing response information on this endpoint were imputed as non-response (non-responder imputation).