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

Primary Purpose

Migraine

Status

Completed

Phase

Phase 4

Locations

Germany

Study Type

Interventional

Intervention

Erenumab

Topiramate

Erenumab matching placebo

Topiramate matching placebo

About this trial

This is an interventional prevention trial for Migraine focused on measuring Migraine, Episodic migraine, Chronic migraine, Headache, erenumab, topiramate, CAMG 334, Calcitonin Gene-related Peptide, CGRP, CGRP receptor agonist, monoclonal antibody, treatment failure

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key 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)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Erenumab

Topiramate

Arm Description

70 mg and 140 mg Erenumab

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).

Full Information

NCT ID

NCT03828539

First Posted

February 1, 2019

Last Updated

October 7, 2021

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03828539

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Completed

Study Start Date

February 22, 2019 (Actual)

Primary Completion Date

July 29, 2020 (Actual)

Study Completion Date

July 29, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Migraine

Keywords

Migraine, Episodic migraine, Chronic migraine, Headache, erenumab, topiramate, CAMG 334, Calcitonin Gene-related Peptide, CGRP, CGRP receptor agonist, monoclonal antibody, treatment failure

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

777 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Erenumab

Arm Type

Experimental

Arm Description

70 mg and 140 mg Erenumab

Arm Title

Topiramate

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

Erenumab

Other Intervention Name(s)

AMG334

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Topiramate

Other Intervention Name(s)

Topamax

Intervention Description

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

Biological

Intervention Name(s)

Erenumab matching placebo

Intervention Description

Erenumab matching placebo pre-filled syringue administered every 4 weeks

Intervention Type

Drug

Intervention Name(s)

Topiramate matching placebo

Intervention Description

Topiramate matching placebo administered daily

Primary Outcome Measure Information:

Title

Proportion of Patients With Treatment Discontinuation Due to an Adverse Event (AE) During the Double-blind Treatment Epoch/Period (DBTE)

Description

Time Frame

24 Weeks

Secondary Outcome Measure Information:

Title

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)

Description

Time Frame

Baseline, Last three months (month 4, 5, and 6)

Other Pre-specified Outcome Measures:

Title

EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Reduction in the Headache Impact Test (HIT-6) From Baseline to Week 24

Description

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.

Time Frame

Baseline, Week 24

Title

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

Description

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.

Time Frame

Baseline, Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Stuttgart

State/Province

Baden Wuertemberg

ZIP/Postal Code

70178

Country

Germany

Facility Name

Novartis Investigative Site

City

Hannover

State/Province

Niedersachsen

ZIP/Postal Code

30159

Country

Germany

Facility Name

Novartis Investigative Site

City

Aachen

State/Province

Nordrhein-Westfalen

ZIP/Postal Code

52062

Country

Germany

Facility Name

Novartis Investigative Site

City

Alzenau

ZIP/Postal Code

63755

Country

Germany

Facility Name

Novartis Investigative Site

City

Bad Homburg

ZIP/Postal Code

61348

Country

Germany

Facility Name

Novartis Investigative Site

City

Bad Honnef

ZIP/Postal Code

53604

Country

Germany

Facility Name

Novartis Investigative Site

City

Bad Saarow

ZIP/Postal Code

15526

Country

Germany

Facility Name

Novartis Investigative Site

City

Bayreuth

ZIP/Postal Code

95445

Country

Germany

Facility Name

Novartis Investigative Site

City

Bergen

ZIP/Postal Code

18528

Country

Germany

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

10713

Country

Germany

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

120999

Country

Germany

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

12101

Country

Germany

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

12163

Country

Germany

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

12627

Country

Germany

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

13156

Country

Germany

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

14169

Country

Germany

Facility Name

Novartis Investigative Site

City

Bielefeld

ZIP/Postal Code

D 33647

Country

Germany

Facility Name

Novartis Investigative Site

City

Boblingen

ZIP/Postal Code

71032

Country

Germany

Facility Name

Novartis Investigative Site

City

Bochum

ZIP/Postal Code

44791

Country

Germany

Facility Name

Novartis Investigative Site

City

Bonn

ZIP/Postal Code

53111

Country

Germany

Facility Name

Novartis Investigative Site

City

Bonn

ZIP/Postal Code

53177

Country

Germany

Facility Name

Novartis Investigative Site

City

Celle

ZIP/Postal Code

29223

Country

Germany

Facility Name

Novartis Investigative Site

City

Chemnitz

ZIP/Postal Code

09117

Country

Germany

Facility Name

Novartis Investigative Site

City

Dillingen

ZIP/Postal Code

66763

Country

Germany

Facility Name

Novartis Investigative Site

City

Erbach

ZIP/Postal Code

64711

Country

Germany

Facility Name

Novartis Investigative Site

City

Essen

ZIP/Postal Code

45133

Country

Germany

Facility Name

Novartis Investigative Site

City

Essen

ZIP/Postal Code

45147

Country

Germany

Facility Name

Novartis Investigative Site

City

Frankfurt

ZIP/Postal Code

60313

Country

Germany

Facility Name

Novartis Investigative Site

City

Freiburg

ZIP/Postal Code

79098

Country

Germany

Facility Name

Novartis Investigative Site

City

Gelsenkirchen

ZIP/Postal Code

45879

Country

Germany

Facility Name

Novartis Investigative Site

City

Greifswald

ZIP/Postal Code

17475

Country

Germany

Facility Name

Novartis Investigative Site

City

Haar

ZIP/Postal Code

85540

Country

Germany

Facility Name

Novartis Investigative Site

City

Halle

ZIP/Postal Code

06120

Country

Germany

Facility Name

Novartis Investigative Site

City

Hamburg

ZIP/Postal Code

20253

Country

Germany

Facility Name

Novartis Investigative Site

City

Heidelberg

ZIP/Postal Code

69120

Country

Germany

Facility Name

Novartis Investigative Site

City

Heidenheim

ZIP/Postal Code

89518

Country

Germany

Facility Name

Novartis Investigative Site

City

Hoppegarten

ZIP/Postal Code

15366

Country

Germany

Facility Name

Novartis Investigative Site

City

Ibbenbueren

ZIP/Postal Code

49477

Country

Germany

Facility Name

Novartis Investigative Site

City

Jena

ZIP/Postal Code

07740

Country

Germany

Facility Name

Novartis Investigative Site

City

Juelich

ZIP/Postal Code

52428

Country

Germany

Facility Name

Novartis Investigative Site

City

Kassel

ZIP/Postal Code

34121

Country

Germany

Facility Name

Novartis Investigative Site

City

Kassel

Country

Germany

Facility Name

Novartis Investigative Site

City

Kiel

ZIP/Postal Code

24149

Country

Germany

Facility Name

Novartis Investigative Site

City

Koln

ZIP/Postal Code

50935

Country

Germany

Facility Name

Novartis Investigative Site

City

Königstein im Taunus

ZIP/Postal Code

61462

Country

Germany

Facility Name

Novartis Investigative Site

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

Facility Name

Novartis Investigative Site

City

Leipzig

ZIP/Postal Code

04107

Country

Germany

Facility Name

Novartis Investigative Site

City

Luenen

ZIP/Postal Code

44534

Country

Germany

Facility Name

Novartis Investigative Site

City

Mannheim

ZIP/Postal Code

66163

Country

Germany

Facility Name

Novartis Investigative Site

City

Marburg Wehrda

ZIP/Postal Code

35041

Country

Germany

Facility Name

Novartis Investigative Site

City

Mittweida

ZIP/Postal Code

09648

Country

Germany

Facility Name

Novartis Investigative Site

City

Muenchen

ZIP/Postal Code

81377

Country

Germany

Facility Name

Novartis Investigative Site

City

Muenchen

ZIP/Postal Code

81675

Country

Germany

Facility Name

Novartis Investigative Site

City

Muenster

ZIP/Postal Code

48149

Country

Germany

Facility Name

Novartis Investigative Site

City

Neu-Ulm

ZIP/Postal Code

89231

Country

Germany

Facility Name

Novartis Investigative Site

City

Neuburg an der Donau

ZIP/Postal Code

86633

Country

Germany

Facility Name

Novartis Investigative Site

City

Osnabrück

ZIP/Postal Code

49074

Country

Germany

Facility Name

Novartis Investigative Site

City

Pforzheim

ZIP/Postal Code

75172

Country

Germany

Facility Name

Novartis Investigative Site

City

Quakenbrueck

ZIP/Postal Code

49610

Country

Germany

Facility Name

Novartis Investigative Site

City

Regensburg

ZIP/Postal Code

93059

Country

Germany

Facility Name

Novartis Investigative Site

City

Rostock

ZIP/Postal Code

18057

Country

Germany

Facility Name

Novartis Investigative Site

City

Ruelzheim

ZIP/Postal Code

76761

Country

Germany

Facility Name

Novartis Investigative Site

City

Schwerin

ZIP/Postal Code

19053

Country

Germany

Facility Name

Novartis Investigative Site

City

Schwerin

ZIP/Postal Code

19055

Country

Germany

Facility Name

Novartis Investigative Site

City

Seesen

ZIP/Postal Code

38723

Country

Germany

Facility Name

Novartis Investigative Site

City

Siegen

ZIP/Postal Code

57076

Country

Germany

Facility Name

Novartis Investigative Site

City

Sindelfingen

ZIP/Postal Code

71065

Country

Germany

Facility Name

Novartis Investigative Site

City

Stadtroda

ZIP/Postal Code

07646

Country

Germany

Facility Name

Novartis Investigative Site

City

Stuttgart

ZIP/Postal Code

70174

Country

Germany

Facility Name

Novartis Investigative Site

City

Stuttgart

ZIP/Postal Code

70178

Country

Germany

Facility Name

Novartis Investigative Site

City

Stuttgart

ZIP/Postal Code

70182

Country

Germany

Facility Name

Novartis Investigative Site

City

Trier

ZIP/Postal Code

54292

Country

Germany

Facility Name

Novartis Investigative Site

City

Tübingen

ZIP/Postal Code

72076

Country

Germany

Facility Name

Novartis Investigative Site

City

Ulm

ZIP/Postal Code

89073

Country

Germany

Facility Name

Novartis Investigative Site

City

Unterhaching

ZIP/Postal Code

82008

Country

Germany

Facility Name

Novartis Investigative Site

City

Westerstede/Oldenburg

ZIP/Postal Code

26655

Country

Germany

Facility Name

Novartis Investigative Site

City

Wiesbaden

ZIP/Postal Code

65191

Country

Germany

Facility Name

Novartis Investigative Site

City

Wuerzburg

ZIP/Postal Code

97080

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Citations:

PubMed Identifier

36380284

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.

Results Reference

derived

PubMed Identifier

34743579

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.

Results Reference

derived

Links:

URL

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

Description

A Plain Language Trial Summary is available on novartisclinicaltrials.com

Learn more about this trial

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

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

Migraine

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial