Clinical trial NCT03828539: Head-to-head Study of Erenumab Against Topiramate in Patients With Episodic and Chronic Migraine
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Migraine
Keywords: Migraine
Episodic migraine
Chronic migraine
Headache
erenumab
topiramate
CAMG 334
Calcitonin Gene-related Peptide
CGRP
CGRP receptor agonist
monoclonal antibody
treatment failure
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-02-04
Enrollment: 777
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

Eligibility criteria: 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)

Primary outcomes:
measure: Proportion of Patients With Treatment Discontinuation Due to an Adverse Event (AE) During the Double-blind Treatment Epoch/Period (DBTE)
timeFrame: 24 Weeks
Secondary outcomes:
measure: 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)
timeFrame: Baseline, Last three months (month 4, 5, and 6)
Other outcomes:
measure: EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Reduction in the Headache Impact Test (HIT-6) From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: 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
timeFrame: Baseline, Week 24
Locations:
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
state: Baden Wuertemberg
city: Hannover
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Aachen
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Alzenau
country: Germany
facility: Novartis Investigative Site
city: Bad Homburg
country: Germany
facility: Novartis Investigative Site
city: Bad Honnef
country: Germany
facility: Novartis Investigative Site
city: Bad Saarow
country: Germany
facility: Novartis Investigative Site
city: Bayreuth
country: Germany
facility: Novartis Investigative Site
city: Bergen
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bielefeld
country: Germany
facility: Novartis Investigative Site
city: Boblingen
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Celle
country: Germany
facility: Novartis Investigative Site
city: Chemnitz
country: Germany
facility: Novartis Investigative Site
city: Dillingen
country: Germany
facility: Novartis Investigative Site
city: Erbach
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Gelsenkirchen
country: Germany
facility: Novartis Investigative Site
city: Greifswald
country: Germany
facility: Novartis Investigative Site
city: Haar
country: Germany
facility: Novartis Investigative Site
city: Halle
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Heidenheim
country: Germany
facility: Novartis Investigative Site
city: Hoppegarten
country: Germany
facility: Novartis Investigative Site
city: Ibbenbueren
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Juelich
country: Germany
facility: Novartis Investigative Site
city: Kassel
country: Germany
facility: Novartis Investigative Site
city: Kassel
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Koln
country: Germany
facility: Novartis Investigative Site
city: Königstein im Taunus
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Luenen
country: Germany
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
city: Marburg Wehrda
country: Germany
facility: Novartis Investigative Site
city: Mittweida
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Neu-Ulm
country: Germany
facility: Novartis Investigative Site
city: Neuburg an der Donau
country: Germany
facility: Novartis Investigative Site
city: Osnabrück
country: Germany
facility: Novartis Investigative Site
city: Pforzheim
country: Germany
facility: Novartis Investigative Site
city: Quakenbrueck
country: Germany
facility: Novartis Investigative Site
city: Regensburg
country: Germany
facility: Novartis Investigative Site
city: Rostock
country: Germany
facility: Novartis Investigative Site
city: Ruelzheim
country: Germany
facility: Novartis Investigative Site
city: Schwerin
country: Germany
facility: Novartis Investigative Site
city: Schwerin
country: Germany
facility: Novartis Investigative Site
city: Seesen
country: Germany
facility: Novartis Investigative Site
city: Siegen
country: Germany
facility: Novartis Investigative Site
city: Sindelfingen
country: Germany
facility: Novartis Investigative Site
city: Stadtroda
country: Germany
facility: Novartis Investigative Site
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
city: Trier
country: Germany
facility: Novartis Investigative Site
city: Tübingen
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Unterhaching
country: Germany
facility: Novartis Investigative Site
city: Westerstede/Oldenburg
country: Germany
facility: Novartis Investigative Site
city: Wiesbaden
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Ehrlich M, Hentschke C, Sieder C, Maier-Peuschel M, Reuter U. Erenumab versus topiramate: post hoc efficacy analysis from the HER-MES study. J Headache Pain. 2022 Nov 15;23(1):141. doi: 10.1186/s10194-022-01511-y.
citation: Reuter U, Ehrlich M, Gendolla A, Heinze A, Klatt J, Wen S, Hours-Zesiger P, Nickisch J, Sieder C, Hentschke C, Maier-Peuschel M. Erenumab versus topiramate for the prevention of migraine - a randomised, double-blind, active-controlled phase 4 trial. Cephalalgia. 2022 Feb;42(2):108-118. doi: 10.1177/03331024211053571. Epub 2021 Nov 7.