Erenumab - Comprehensive Assessment of Efficacy in (High-Frequency) Episodic Migraine (EMBRACE)

Amgen

Status and phase: Completed; Phase 4

Conditions: Migraine

Treatments: Drug: Placebo; Drug: Erenumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04252742

20190008

2019-003646-33 (EudraCT Number)

Details and patient eligibility

About

The primary objective of this study is to evaluate the treatment benefit of erenumab on headache duration of at least moderate pain intensity.

Enrollment: 512 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key inclusion criteria include:

• Age greater than or equal to 18 years upon entry into initial screening.
• Documented history of migraine with or without aura according to the International Headache Society (IHS) International Classification of Headache Disorders, Third Edition (ICHD-III) for greater than or equal to 12 months.
• Have high-frequency episodic migraine (HFEM): Defined as history of ≥ 7 to < 15 migraine days and < 15 headache days per month on average during the 3 months prior to screening.
• History of ≥ 4 migraine attacks of at least moderate severity per month on average during the 3 months prior to screening.
• History of treatment failure with at least 1 preventive treatment for migraine. Failure of preventive treatment for migraine is defined as treatment discontinuation due to lack of efficacy, adverse event, or general poor tolerability.
• Regular use of an oral triptan (using only eletriptan, rizatriptan, sumatriptan, or zolmitriptan) for acute migraine treatment, and typically initiating acute treatment with an oral triptan on > 50% of attacks of at least moderate pain intensity. Regular use is defined as ≥ 4 days of oral triptan use per month during the 3 months prior to screening.

Key exclusion criteria include:

• History of hemiplegic migraine, cluster headache, or other trigeminal autonomic cephalalgia.

• Has any medical contraindication to the use of an oral triptan.

• Previously treated with erenumab.

• Previously treated with a gepant (small molecule calcitonin gene related peptide receptor [CGRP-R] antagonist) in a preventive fashion in a manner consistent with migraine prevention that either:

  1. In the opinion of the investigator, did not offer any evidence of a therapeutic response or
  2. Was discontinued for less than 12 weeks from the date of initial screening or
  3. Was previously discontinued due to a known adverse drug reaction

• Currently being treated with lasmiditan and/or a gepant in the acute setting.

• No therapeutic response with greater than 4 of the defined medication categories after an adequate therapeutic trial.

• Currently has a history of consistent excellent response to oral triptans, defined as achievement of pain-freedom in ≤ 1 hour for ≥ 50% of treated attacks of at least moderate pain intensity during the 3 months prior to screening.

• Use of triptans administered via a non-oral (e.g. subcutaneous [SC] or intranasal delivery systems) or sublingual route at the time of screening, during the run-in and baseline periods, and throughout the study duration.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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512 participants in 2 patient groups

Erenumab

Experimental group

Description:

The 4-month DBTP has 2 phases: Main double-blind treatment phase (M-DBTP, months 1 to 3) that will assess the effect of erenumab on metrics such as time spent in at least moderate pain, peak migraine severity, and functional impairment. Exploratory DBTP (E-DBTP, month 4) that will assess the impact of erenumab on the acute response to treatment with oral triptan therapy as well as non-ictal burden.

Treatment:

Drug: Erenumab

Placebo

Experimental group

Description:

The 4-month DBTP has 2 phases: Main DBTP (M-DBTP, months 1 to 3) that will assess the effect of erenumab on metrics such as time spent in at least moderate pain, peak migraine severity, and functional impairment. Exploratory DBTP (E-DBTP, month 4) that will assess the impact of erenumab on the acute response to treatment with oral triptan therapy as well as non-ictal burden.

Treatment:

Drug: Placebo