Head-to-head Study of Erenumab Against Topiramate in Patients With Episodic and Chronic Migraine (HER-MES)
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|ClinicalTrials.gov Identifier: NCT03828539|
Recruitment Status : Completed
First Posted : February 4, 2019
Results First Posted : August 9, 2021
Last Update Posted : October 11, 2021
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|Condition or disease||Intervention/treatment||Phase|
|Migraine||Biological: Erenumab Drug: Topiramate Biological: Erenumab matching placebo Drug: Topiramate matching placebo||Phase 4|
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).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||777 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|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|
|Actual Study Start Date :||February 22, 2019|
|Actual Primary Completion Date :||July 29, 2020|
|Actual Study Completion Date :||July 29, 2020|
70 mg and 140 mg Erenumab
70mg/1mL (70 mg) or 2x70mg/1mL (140 mg) in pre-filled syringe, administered every 4 weeks
Other Name: AMG334
Biological: Erenumab matching placebo
Erenumab matching placebo pre-filled syringue administered every 4 weeks
Active Comparator: Topiramate
Topiramate in the highest tolerated dose (50 - 100 mg/day)
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.
Other Name: Topamax
Drug: Topiramate matching placebo
Topiramate matching placebo administered daily
- Proportion of Patients With Treatment Discontinuation Due to an Adverse Event (AE) During the Double-blind Treatment Epoch/Period (DBTE) [ Time Frame: 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.
- 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) [ Time Frame: 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).
- EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Reduction in the Headache Impact Test (HIT-6) From Baseline to Week 24 [ Time Frame: Baseline, 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.
- 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 [ Time Frame: Baseline, 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years to 65 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03828539
|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|
Documents provided by Novartis ( Novartis Pharmaceuticals ):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Novartis Pharmaceuticals|
|Other Study ID Numbers:||
2018-000943-15 ( EudraCT Number )
|First Posted:||February 4, 2019 Key Record Dates|
|Results First Posted:||August 9, 2021|
|Last Update Posted:||October 11, 2021|
|Last Verified:||October 2021|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
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
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
|Product Manufactured in and Exported from the U.S.:||Yes|
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