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

Migraine Clinical Trial

— HER-MES  

Official title:

Head-to-head Study of Erenumab Against topiRamate-a Double-blind, Double Dummy Migraine Study to Assess Tolerability and Efficacy in a patiEnt -Centered Setting

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03828539
• Other study ID #: CAMG334ADE01
• Secondary ID: 2018-000943-15
• Status: Completed
• Phase: Phase 4
• Start date: February 22, 2019
• Est. completion date: July 29, 2020

Study information

• Verified date: October 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 777
• Est. completion date: July 29, 2020
• Est. primary completion date: July 29, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Key Inclusion Criteria:

1. Documented history of migraine in the 12 months prior to screen

2. at least 4 days per month of migraine symptoms

3. >=80% diary compliance during the Baseline period

4. Patients must be either naïve or not suitable or have failed previous migraine prophylactic treatments

Key Exclusion Criteria:

1. Older than 50 years of age at migraine onset

2. Pregnant or nursing

3. History of cluster or hemiplegic headache

4. History or evidence of major psychiatric disorder

5. Score of 19 or higher on Beck Depression Inventory (BDI)

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

Intervention

Biological:
• Erenumab
70mg/1mL (70 mg) or 2x70mg/1mL (140 mg) in pre-filled syringe, administered every 4 weeks

Drug:
• Topiramate
Film-coated tablet taken orally: 25 mg administered once daily (first week of titration phase). After the first week, titration was done according to the summary of product characteristics (SmPC) in 25 mg increments each week and aimed to reach the recommended daily treatment dose of 100 mg (50/75/100 mg). 50/75/100 mg were administered twice daily during titration phase and maintenance phase.

Biological:
• Erenumab matching placebo
Erenumab matching placebo pre-filled syringue administered every 4 weeks

Drug:
• Topiramate matching placebo
Topiramate matching placebo administered daily

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Aachen	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Alzenau
Germany	Novartis Investigative Site	Bad Homburg
Germany	Novartis Investigative Site	Bad Honnef
Germany	Novartis Investigative Site	Bad Saarow
Germany	Novartis Investigative Site	Bayreuth
Germany	Novartis Investigative Site	Bergen
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Boblingen
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Celle
Germany	Novartis Investigative Site	Chemnitz
Germany	Novartis Investigative Site	Dillingen
Germany	Novartis Investigative Site	Erbach
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Gelsenkirchen
Germany	Novartis Investigative Site	Greifswald
Germany	Novartis Investigative Site	Haar
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover	Niedersachsen
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Heidenheim
Germany	Novartis Investigative Site	Hoppegarten
Germany	Novartis Investigative Site	Ibbenbueren
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Juelich
Germany	Novartis Investigative Site	Kassel
Germany	Novartis Investigative Site	Kassel
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Koln
Germany	Novartis Investigative Site	Königstein im Taunus
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Luenen
Germany	Novartis Investigative Site	Mannheim
Germany	Novartis Investigative Site	Marburg Wehrda
Germany	Novartis Investigative Site	Mittweida
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Neu-Ulm
Germany	Novartis Investigative Site	Neuburg an der Donau
Germany	Novartis Investigative Site	Osnabrück
Germany	Novartis Investigative Site	Pforzheim
Germany	Novartis Investigative Site	Quakenbrueck
Germany	Novartis Investigative Site	Regensburg
Germany	Novartis Investigative Site	Rostock
Germany	Novartis Investigative Site	Ruelzheim
Germany	Novartis Investigative Site	Schwerin
Germany	Novartis Investigative Site	Schwerin
Germany	Novartis Investigative Site	Seesen
Germany	Novartis Investigative Site	Siegen
Germany	Novartis Investigative Site	Sindelfingen
Germany	Novartis Investigative Site	Stadtroda
Germany	Novartis Investigative Site	Stuttgart
Germany	Novartis Investigative Site	Stuttgart
Germany	Novartis Investigative Site	Stuttgart
Germany	Novartis Investigative Site	Stuttgart	Baden Wuertemberg
Germany	Novartis Investigative Site	Trier
Germany	Novartis Investigative Site	Tübingen
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Unterhaching
Germany	Novartis Investigative Site	Westerstede/Oldenburg
Germany	Novartis Investigative Site	Wiesbaden
Germany	Novartis Investigative Site	Wuerzburg

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Reduction in the Headache Impact Test (HIT-6) From Baseline to Week 24	The HIT-6 is a widely used patient-reported outcome measure that assesses the negative effects of headaches on normal activity. Six items assess the frequency of pain severity, headaches limiting daily activity (household, work, school, and social), wanting to lie down when headache is experienced, feeling too tired to work or do daily activities because of headache, feeling "fed up" or irritated because of headache, and headaches limiting ability to concentrate or work on daily activities. Each of the 6 questions is responded to using 1 of 5 response categories: "never," "rarely," "sometimes," "very often," or "always." For each HIT-6 item, 6, 8, 10, 11, or 13 points, respectively, are assigned to the response provided. These points are summed to produce a total HIT-6 score that ranges from 36 to 78. HIT-6 scores are categorized into 4 grades: little or no impact (49 or less), some impact (50 - 55), substantial impact (56 - 59), and severe impact (60 - 78) due to headache.	Baseline, Week 24
Other	EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Increase in the Medical Outcome Short Form Health Survey Version 2 (SF-36) From Baseline to Week 24	The SF-36 is a widely used and extensively studied instrument to measure health-related quality of life (HRQoL) among healthy subjects and patients with acute and chronic conditions. It consists of eight subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) also can be computed. The SF-36 has proven useful in monitoring general and specific populations, comparing the relative burden of different disease, differentiating the health benefits produced by different treatments, and in screening individual patients. The purpose of the SF-36 in this study was to assess the HRQoL of patients. Given the nature of this disease and the 4-weekly assessment, the SF-36 version 2, with a 4-week recall period, was used in this study.	Baseline, Week 24
Primary	Proportion of Patients With Treatment Discontinuation Due to an Adverse Event (AE) During the Double-blind Treatment Epoch/Period (DBTE)	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.	24 Weeks
Secondary	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)	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).	Baseline, Last three months (month 4, 5, and 6)

External Links

•   A Plain Language Trial Summary is available on novartisclinicaltrials.com