Trial Outcomes & Findings for Head-to-head Study of Erenumab Against Topiramate in Patients With Episodic and Chronic Migraine (NCT NCT03828539)

Last Updated: 2021-10-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

777 participants

Primary outcome timeframe

24 Weeks

Results posted on

2021-10-11

Participant Flow

82 centers in Germany enrolled patients.

A total of 777 patients were randomized to receive either erenumab (389 patients) or topiramate (388 patients).

Participant milestones

Participant milestones
Measure	Erenumab 70 mg and 140 mg Erenumab	Topiramate Topiramate in the highest tolerated dose (50 - 100 mg/day)
Overall Study STARTED	389	388
Overall Study Full Analysis Set (FAS)	388	388
Overall Study Safety Analysis Set (SAF)	388	388
Overall Study COMPLETED	373	366
Overall Study NOT COMPLETED	16	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Erenumab 70 mg and 140 mg Erenumab	Topiramate Topiramate in the highest tolerated dose (50 - 100 mg/day)
Overall Study Adverse Event	3	12
Overall Study Patient's/guardian's decision	3	5
Overall Study Lost to Follow-up	4	2
Overall Study Protocol Violation	3	2
Overall Study Withdrawal of informed consent	2	1
Overall Study New therapy for study indication	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Erenumab n=388 Participants 70 mg and 140 mg Erenumab	Topiramate n=388 Participants Topiramate in the highest tolerated dose (50 - 100 mg/day)	Total n=776 Participants Total of all reporting groups
Age, Continuous	40.8 Years STANDARD_DEVIATION 12.4 • n=5 Participants	40.7 Years STANDARD_DEVIATION 12.4 • n=7 Participants	40.7 Years STANDARD_DEVIATION 12.4 • n=5 Participants
Sex: Female, Male Female	331 Participants n=5 Participants	335 Participants n=7 Participants	666 Participants n=5 Participants
Sex: Female, Male Male	57 Participants n=5 Participants	53 Participants n=7 Participants	110 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	383 Participants n=5 Participants	387 Participants n=7 Participants	770 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Baseline Monthly Migraine Days (MMDs) categories < 4 days	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Baseline Monthly Migraine Days (MMDs) categories 4 to 7 days	94 Participants n=5 Participants	92 Participants n=7 Participants	186 Participants n=5 Participants
Baseline Monthly Migraine Days (MMDs) categories 8 to 14 days	248 Participants n=5 Participants	254 Participants n=7 Participants	502 Participants n=5 Participants
Baseline Monthly Migraine Days (MMDs) categories >= 15 days	43 Participants n=5 Participants	42 Participants n=7 Participants	85 Participants n=5 Participants
Baseline Monthly Migraine Days (MMDs) categories Missing	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 Weeks

Population: Full Analysis Set (FAS)

Outcome measures

Outcome measures
Measure	Erenumab n=388 Participants 70 mg and 140 mg Erenumab	Topiramate n=388 Participants Topiramate in the highest tolerated dose (50 - 100 mg/day)
Proportion of Patients With Treatment Discontinuation Due to an Adverse Event (AE) During the Double-blind Treatment Epoch/Period (DBTE)	41 Participants	151 Participants

SECONDARY outcome

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

Population: Full Analysis Set (FAS)

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).

Outcome measures

Outcome measures
Measure	Erenumab n=388 Participants 70 mg and 140 mg Erenumab	Topiramate n=388 Participants Topiramate in the highest tolerated dose (50 - 100 mg/day)
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)	215 Participants	121 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set (FAS)

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.

Outcome measures

Outcome measures
Measure	Erenumab n=388 Participants 70 mg and 140 mg Erenumab	Topiramate n=388 Participants Topiramate in the highest tolerated dose (50 - 100 mg/day)
EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Reduction in the Headache Impact Test (HIT-6) From Baseline to Week 24	280 Participants	209 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set (FAS)

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.

Outcome measures

Outcome measures
Measure	Erenumab n=388 Participants 70 mg and 140 mg Erenumab	Topiramate n=388 Participants Topiramate in the highest tolerated dose (50 - 100 mg/day)
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 Physical Component Summary (PCS)	185 Participants	145 Participants
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 Mental Component Summary (MCS)	98 Participants	65 Participants

Adverse Events

Erenumab

Serious events: 10 serious events

Other events: 253 other events

Deaths: 0 deaths

Topiramate

Serious events: 19 serious events

Other events: 331 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Erenumab n=388 participants at risk 70 mg and 140 mg Erenumab	Topiramate n=388 participants at risk Topiramate in the highest tolerated dose (50 - 100 mg/day)
Ear and labyrinth disorders Vertigo	5.2% 20/388 • 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). 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).	6.2% 24/388 • 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). 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).
Gastrointestinal disorders Abdominal pain upper	5.7% 22/388 • 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). 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).	5.9% 23/388 • 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). 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).
Gastrointestinal disorders Constipation	12.4% 48/388 • 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). 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).	3.1% 12/388 • 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). 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).
Gastrointestinal disorders Diarrhoea	5.2% 20/388 • 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). 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).	7.5% 29/388 • 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). 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).
Gastrointestinal disorders Nausea	9.3% 36/388 • 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). 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).	18.3% 71/388 • 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). 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).
General disorders Fatigue	11.3% 44/388 • 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). 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).	19.1% 74/388 • 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). 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).
Infections and infestations Nasopharyngitis	37.4% 145/388 • 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). 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).	38.7% 150/388 • 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). 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).
Investigations Weight decreased	1.3% 5/388 • 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). 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).	5.7% 22/388 • 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). 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).
Metabolism and nutrition disorders Decreased appetite	2.1% 8/388 • 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). 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).	10.1% 39/388 • 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). 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).
Musculoskeletal and connective tissue disorders Back pain	5.4% 21/388 • 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). 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).	5.2% 20/388 • 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). 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).
Nervous system disorders Disturbance in attention	4.6% 18/388 • 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). 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).	16.2% 63/388 • 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). 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).
Nervous system disorders Dizziness	7.2% 28/388 • 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). 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).	15.5% 60/388 • 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). 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).
Nervous system disorders Dysgeusia	0.77% 3/388 • 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). 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).	5.9% 23/388 • 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). 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).
Nervous system disorders Paraesthesia	4.4% 17/388 • 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). 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).	41.0% 159/388 • 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). 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).
Nervous system disorders Taste disorder	0.00% 0/388 • 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). 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).	6.7% 26/388 • 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). 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).
Psychiatric disorders Sleep disorder	5.2% 20/388 • 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). 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).	2.1% 8/388 • 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). 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).