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

NCT ID: NCT03828539

Last Updated: 2021-10-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 777 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-22
• Study Completion Date: 2020-07-29

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).

Conditions

Migraine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Erenumab

70 mg and 140 mg Erenumab

Group Type: EXPERIMENTAL

Erenumab

Intervention Type: BIOLOGICAL

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

Erenumab matching placebo

Intervention Type: BIOLOGICAL

Erenumab matching placebo pre-filled syringue administered every 4 weeks

Topiramate

Topiramate in the highest tolerated dose (50 - 100 mg/day)

Group Type: ACTIVE_COMPARATOR

Topiramate

Intervention Type: DRUG

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.

Topiramate matching placebo

Intervention Type: DRUG

Topiramate matching placebo administered daily

Interventions

Erenumab

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

Intervention Type: BIOLOGICAL

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.

Intervention Type: DRUG

Erenumab matching placebo

Erenumab matching placebo pre-filled syringue administered every 4 weeks

Intervention Type: BIOLOGICAL

Topiramate matching placebo

Topiramate matching placebo administered daily

Intervention Type: DRUG

Other Intervention Names

AMG334; Topamax

Eligibility Criteria

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

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Stuttgart, Baden-Wurttemberg, Germany

Novartis Investigative Site

Marburg Wehrda, Germany, Germany

Novartis Investigative Site

Hanover, Lower Saxony, Germany

Novartis Investigative Site

Aachen, North Rhine-Westphalia, Germany

Novartis Investigative Site

Alzenau in Unterfranken, , 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

Bochum, , Germany

Novartis Investigative Site

Bonn, , Germany

Novartis Investigative Site

Bonn, , Germany

Novartis Investigative Site

Böblingen, , Germany

Novartis Investigative Site

Celle, , Germany

Novartis Investigative Site

Chemnitz, , Germany

Novartis Investigative Site

Cologne, , Germany

Novartis Investigative Site

Dillingen, , Germany

Novartis Investigative Site

Erbach im Odenwald, , Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Frankfurt, , Germany

Novartis Investigative Site

Freiburg im Breisgau, , 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

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

Jülich, , Germany

Novartis Investigative Site

Kassel, , Germany

Novartis Investigative Site

Kassel, , Germany

Novartis Investigative Site

Kiel, , Germany

Novartis Investigative Site

Königstein im Taunus, , Germany

Novartis Investigative Site

Leipzig, , Germany

Novartis Investigative Site

Leipzig, , Germany

Novartis Investigative Site

Lünen, , Germany

Novartis Investigative Site

Mannheim, , Germany

Novartis Investigative Site

Mittweida, , Germany

Novartis Investigative Site

München, , Germany

Novartis Investigative Site

München, , Germany

Novartis Investigative Site

Münster, , 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

Quakenbrück, , Germany

Novartis Investigative Site

Regensburg, , Germany

Novartis Investigative Site

Rostock, , Germany

Novartis Investigative Site

Rülzheim, , 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

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

Würzburg, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 36380284 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34743579 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=941

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Other Identifiers

2018-000943-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAMG334ADE01

Identifier Type: -

Identifier Source: org_study_id