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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
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition Migraine
Interventions Biological: Erenumab
Drug: Topiramate
Biological: Erenumab matching placebo
Drug: Topiramate matching placebo
Enrollment 777
Recruitment Details 82 centers in Germany enrolled patients.
Pre-assignment Details A total of 777 patients were randomized to receive either erenumab (389 patients) or topiramate (388 patients).
Arm/Group Title Erenumab Topiramate
Hide Arm/Group Description 70 mg and 140 mg Erenumab Topiramate in the highest tolerated dose (50 - 100 mg/day)
Period Title: Overall Study
Started [1] 389 388
Full Analysis Set (FAS) [2] 388 388
Safety Analysis Set (SAF) [3] 388 388
Completed 373 366
Not Completed 16 22
Reason Not Completed
Adverse Event             3             12
Patient's/guardian's decision             3             5
Lost to Follow-up             4             2
Protocol Violation             3             2
Withdrawal of informed consent             2             1
New therapy for study indication             1             0
[1]
All patients who received a randomization number, regardless of receiving study medication were included in the Randomized Set
[2]
All patients who received at least one dose of active study medication. In FAS, patients were analyzed according to randomized treatment, regardless of the actual treatment received.
[3]
All randomized patients who received at least one dose of active study medication. In the SAF, patients were analyzed based on actual treatment received.
Arm/Group Title Erenumab Topiramate Total
Hide Arm/Group Description 70 mg and 140 mg Erenumab Topiramate in the highest tolerated dose (50 - 100 mg/day) Total of all reporting groups
Overall Number of Baseline Participants 388 388 776
Hide Baseline Analysis Population Description
Demographic variables and other baseline characteristics were summarized for each randomized treatment group and for all patients (total) using the Full Analysis set (FAS)
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 388 participants 388 participants 776 participants
40.8  (12.4) 40.7  (12.4) 40.7  (12.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 388 participants 388 participants 776 participants
Female
331
  85.3%
335
  86.3%
666
  85.8%
Male
57
  14.7%
53
  13.7%
110
  14.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 388 participants 388 participants 776 participants
Caucasian 383 387 770
Asian 1 0 1
Unknown 1 0 1
Other 3 1 4
Baseline Monthly Migraine Days (MMDs) categories   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 388 participants 388 participants 776 participants
< 4 days
2
   0.5%
0
   0.0%
2
   0.3%
4 to 7 days
94
  24.2%
92
  23.7%
186
  24.0%
8 to 14 days
248
  63.9%
254
  65.5%
502
  64.7%
>= 15 days
43
  11.1%
42
  10.8%
85
  11.0%
Missing
1
   0.3%
0
   0.0%
1
   0.1%
[1]
Measure Description: Monthly migraine days at baseline are the number of migraine days in the baseline period that are normalized in a 28-day interval. Monthly migraine days after baseline are the number of migraine days between each monthly IMP dose that are normalized in a 28-day interval. Days without eDiary data in each normalized monthly interval were prorated.
1.Primary Outcome
Title Proportion of Patients With Treatment Discontinuation Due to an Adverse Event (AE) During the Double-blind Treatment Epoch/Period (DBTE)
Hide Description 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.
Time Frame 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title Erenumab Topiramate
Hide Arm/Group Description:
70 mg and 140 mg Erenumab
Topiramate in the highest tolerated dose (50 - 100 mg/day)
Overall Number of Participants Analyzed 388 388
Measure Type: Count of Participants
Unit of Measure: Participants
41
  10.6%
151
  38.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Erenumab, Topiramate
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Regression, Logistic
Comments Odds ratio is obtained from a logistic regression model that includes treatment group and stratification factor (MMD at baseline)
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
0.13 to 0.27
Estimation Comments [Not Specified]
2.Secondary Outcome
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)
Hide Description 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).
Time Frame Baseline, Last three months (month 4, 5, and 6)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title Erenumab Topiramate
Hide Arm/Group Description:
70 mg and 140 mg Erenumab
Topiramate in the highest tolerated dose (50 - 100 mg/day)
Overall Number of Participants Analyzed 388 388
Measure Type: Count of Participants
Unit of Measure: Participants
215
  55.4%
121
  31.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Erenumab, Topiramate
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Regression, Logistic
Comments Odds ratio is obtained from a logistic regression model that includes treatment group and stratification factor (MMD at baseline)
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.76
Confidence Interval (2-Sided) 95%
2.06 to 3.71
Estimation Comments [Not Specified]
3.Other Pre-specified Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title Erenumab Topiramate
Hide Arm/Group Description:
70 mg and 140 mg Erenumab
Topiramate in the highest tolerated dose (50 - 100 mg/day)
Overall Number of Participants Analyzed 388 388
Measure Type: Count of Participants
Unit of Measure: Participants
280
  72.2%
209
  53.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Erenumab, Topiramate
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Regression, Logistic
Comments Odds ratio is obtained from a logistic regression model that includes treatment group and stratification factor (MMD at baseline)
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.30
Confidence Interval (2-Sided) 95%
1.70 to 3.12
Estimation Comments [Not Specified]
4.Other Pre-specified Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)
Arm/Group Title Erenumab Topiramate
Hide Arm/Group Description:
70 mg and 140 mg Erenumab
Topiramate in the highest tolerated dose (50 - 100 mg/day)
Overall Number of Participants Analyzed 388 388
Measure Type: Count of Participants
Unit of Measure: Participants
Physical Component Summary (PCS)
185
  47.7%
145
  37.4%
Mental Component Summary (MCS)
98
  25.3%
65
  16.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Erenumab, Topiramate
Comments Physical Component Summary (PCS)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments Odds ratio is obtained from a logistic regression model that includes treatment group and stratification factor (MMD at baseline)
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.75
Confidence Interval (2-Sided) 95%
1.26 to 2.43
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Erenumab, Topiramate
Comments Mental Component Summary (MCS)
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Regression, Logistic
Comments Odds ratio is obtained from a logistic regression model that includes treatment group and stratification factor (MMD at baseline)
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.79
Confidence Interval (2-Sided) 95%
1.29 to 2.69
Estimation Comments [Not Specified]
Time Frame Adverse events were collected from first dose of study treatment until 8 weeks after the last Investigational Medicinal product (IMP) injection, assessed up to approximately 33 weeks (treatment duration ranged from 4.0 to 25.1 weeks).
Adverse Event Reporting Description Any sign or symptom that occurs during the study treatment until 8 weeks after the last Investigational Medicinal product (IMP) injection. Maximum exposure to study treatments = 25 weeks (Erenumab treatment group) and 25.1 weeks (Topiramate treatment group).
 
Arm/Group Title Erenumab Topiramate
Hide Arm/Group Description 70 mg and 140 mg Erenumab Topiramate in the highest tolerated dose (50 - 100 mg/day)
All-Cause Mortality
Erenumab Topiramate
Affected / at Risk (%) Affected / at Risk (%)
Total   0/388 (0.00%)   0/388 (0.00%) 
Hide Serious Adverse Events
Erenumab Topiramate
Affected / at Risk (%) Affected / at Risk (%)
Total   10/388 (2.58%)   19/388 (4.90%) 
Eye disorders     
Angle closure glaucoma  1  0/388 (0.00%)  1/388 (0.26%) 
Retinal detachment  1  0/388 (0.00%)  1/388 (0.26%) 
Rhegmatogenous retinal detachment  1  0/388 (0.00%)  1/388 (0.26%) 
Gastrointestinal disorders     
Gastritis  1  0/388 (0.00%)  1/388 (0.26%) 
Irritable bowel syndrome  1  0/388 (0.00%)  1/388 (0.26%) 
Mechanical ileus  1  1/388 (0.26%)  0/388 (0.00%) 
Obstructive defaecation  1  1/388 (0.26%)  0/388 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis  1  0/388 (0.00%)  1/388 (0.26%) 
Immune system disorders     
Anaphylactic shock  1  0/388 (0.00%)  1/388 (0.26%) 
Infections and infestations     
Appendicitis  1  0/388 (0.00%)  1/388 (0.26%) 
Bacteriuria  1  0/388 (0.00%)  1/388 (0.26%) 
Gastroenteritis  1  0/388 (0.00%)  1/388 (0.26%) 
Gastrointestinal infection  1  0/388 (0.00%)  1/388 (0.26%) 
Influenza  1  0/388 (0.00%)  1/388 (0.26%) 
Nasopharyngitis  1  0/388 (0.00%)  1/388 (0.26%) 
Papilloma viral infection  1  1/388 (0.26%)  0/388 (0.00%) 
Parasitic gastroenteritis  1  0/388 (0.00%)  1/388 (0.26%) 
Pyelonephritis  1  0/388 (0.00%)  1/388 (0.26%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  0/388 (0.00%)  1/388 (0.26%) 
Concussion  1  0/388 (0.00%)  1/388 (0.26%) 
Contusion  1  1/388 (0.26%)  0/388 (0.00%) 
Fall  1  1/388 (0.26%)  0/388 (0.00%) 
Ligament rupture  1  1/388 (0.26%)  0/388 (0.00%) 
Limb injury  1  1/388 (0.26%)  0/388 (0.00%) 
Skin laceration  1  1/388 (0.26%)  0/388 (0.00%) 
Sternal fracture  1  1/388 (0.26%)  0/388 (0.00%) 
Tendon injury  1  1/388 (0.26%)  0/388 (0.00%) 
Investigations     
Weight decreased  1  0/388 (0.00%)  1/388 (0.26%) 
Metabolism and nutrition disorders     
Decreased appetite  1  0/388 (0.00%)  1/388 (0.26%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion  1  1/388 (0.26%)  0/388 (0.00%) 
Lumbar spinal stenosis  1  0/388 (0.00%)  1/388 (0.26%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Fibroadenoma of breast  1  0/388 (0.00%)  1/388 (0.26%) 
Nervous system disorders     
Migraine  1  0/388 (0.00%)  1/388 (0.26%) 
Migraine with aura  1  1/388 (0.26%)  0/388 (0.00%) 
Syncope  1  0/388 (0.00%)  1/388 (0.26%) 
Psychiatric disorders     
Depression  1  0/388 (0.00%)  1/388 (0.26%) 
Major depression  1  1/388 (0.26%)  0/388 (0.00%) 
Reproductive system and breast disorders     
Cervical dysplasia  1  1/388 (0.26%)  0/388 (0.00%) 
Dysmenorrhoea  1  1/388 (0.26%)  0/388 (0.00%) 
Endometriosis  1  0/388 (0.00%)  1/388 (0.26%) 
1
Term from vocabulary, MedDRA (23.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Erenumab Topiramate
Affected / at Risk (%) Affected / at Risk (%)
Total   253/388 (65.21%)   331/388 (85.31%) 
Ear and labyrinth disorders     
Vertigo  1  20/388 (5.15%)  24/388 (6.19%) 
Gastrointestinal disorders     
Abdominal pain upper  1  22/388 (5.67%)  23/388 (5.93%) 
Constipation  1  48/388 (12.37%)  12/388 (3.09%) 
Diarrhoea  1  20/388 (5.15%)  29/388 (7.47%) 
Nausea  1  36/388 (9.28%)  71/388 (18.30%) 
General disorders     
Fatigue  1  44/388 (11.34%)  74/388 (19.07%) 
Infections and infestations     
Nasopharyngitis  1  145/388 (37.37%)  150/388 (38.66%) 
Investigations     
Weight decreased  1  5/388 (1.29%)  22/388 (5.67%) 
Metabolism and nutrition disorders     
Decreased appetite  1  8/388 (2.06%)  39/388 (10.05%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  21/388 (5.41%)  20/388 (5.15%) 
Nervous system disorders     
Disturbance in attention  1  18/388 (4.64%)  63/388 (16.24%) 
Dizziness  1  28/388 (7.22%)  60/388 (15.46%) 
Dysgeusia  1  3/388 (0.77%)  23/388 (5.93%) 
Paraesthesia  1  17/388 (4.38%)  159/388 (40.98%) 
Taste disorder  1  0/388 (0.00%)  26/388 (6.70%) 
Psychiatric disorders     
Sleep disorder  1  20/388 (5.15%)  8/388 (2.06%) 
1
Term from vocabulary, MedDRA (23.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT03828539    
Other Study ID Numbers: CAMG334ADE01
2018-000943-15 ( EudraCT Number )
First Submitted: February 1, 2019
First Posted: February 4, 2019
Results First Submitted: July 16, 2021
Results First Posted: August 9, 2021
Last Update Posted: October 11, 2021