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

• ClinicalTrials.gov Identifier: NCT04252742
• Recruitment Status: Completed
• First Posted: February 5, 2020
• Last Update Posted: November 8, 2023
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: January 22, 2020
• First Posted Date: February 5, 2020
• Last Update Posted Date: November 8, 2023
• Actual Study Start Date: September 15, 2020
• Actual Primary Completion Date: October 26, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 30, 2020)

Change from baseline in mean monthly hours of at least moderate headache pain intensity, with pain intensity measured by the 11-point NRS scale [ Time Frame: Over months 1, 2, and 3 ]

To evaluate the treatment benefit of erenumab on headache duration of at least moderate pain intensity

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 11, 2022)

• Change from baseline in mean monthly physical function domain score as measured by the Migraine Functional Impact Questionnaire (MFIQ) [ Time Frame: Over months 1, 2, and 3 ]
  To evaluate the treatment benefit of erenumab on functional impairment
• Change from baseline in the mean monthly impact on usual activities domain score as measured by the MFIQ [ Time Frame: Over months 1, 2, and 3 ]
  To evaluate the treatment benefit of erenumab on functional impairment
• Change from baseline in the mean monthly impact on emotional function domain score as measured by the MFIQ [ Time Frame: Over months 1, 2, and 3 ]
  To evaluate the treatment benefit of erenumab on functional impairment
• Change from baseline in the mean monthly impact on social function domain score as measured by the MFIQ [ Time Frame: Over months 1, 2, and 3 ]
  To evaluate the treatment benefit of erenumab on functional impairment
• Change from baseline in mean monthly average duration of at least moderate pain intensity in qualifying migraine attacks, with pain measured by the 11-point NRS scale [ Time Frame: Over months 1, 2, and 3 ]
  To evaluate the treatment benefit of erenumab on duration of migraine pain of at least moderate intensity
• Change from baseline in mean monthly average peak migraine pain intensity as assessed by the 11-point Numeric Rating Scale (NRS) [ Time Frame: Over months 1, 2, and 3 ]
  To evaluate the treatment benefit of erenumab on peak migraine pain intensity

Original Secondary Outcome Measures (submitted: January 30, 2020)

• Change from baseline in mean physical functioning as measured by the Migraine Functional Impact Questionnaire (MFIQ) [ Time Frame: Over months 1, 2, and 3 ]
  To evaluate the treatment benefit of erenumab on functional impairment
• Change from baseline on the Impact of usual activities as measured by the Migraine Functional Impact Questionnaire (MFIQ) [ Time Frame: Over months 1, 2, and 3 ]
  To evaluate the treatment benefit of erenumab on functional impairment
• Change from baseline on the Impact of emotional functioning as measured by the Migraine Functional Impact Questionnaire (MFIQ) [ Time Frame: Over months 1, 2, and 3 ]
  To evaluate the treatment benefit of erenumab on functional impairment
• Change from baseline in mean monthly function as impact on social functioning as measured by the Migraine Functional Impact Questionnaire (MFIQ) [ Time Frame: Over months 1, 2, and 3 ]
  To evaluate the treatment benefit of erenumab on functional impairment
• Change from baseline in mean monthly hours of at least moderate pain intensity per migraine attack, with pain measured by the 11-point NRS scale [ Time Frame: Over months 1, 2, and 3 ]
  To evaluate the treatment benefit of erenumab on duration of migraine pain of at least moderate intensity
• Change from baseline in mean monthly peak migraine pain intensity as assessed by the 11-point Numeric Rating Scale (NRS) [ Time Frame: Over months 1, 2, and 3 ]
  To evaluate the treatment benefit of erenumab on peak migraine pain intensity

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Erenumab - Comprehensive Assessment of Efficacy in (High-Frequency) Episodic Migraine
• Official Title: Comprehensive Assessment of Erenumab Efficacy in Subjects With High Frequency Episodic Migraine With at Least 1 Previously Failed Preventive Treatment: a Global, Double-blind, Placebo-controlled Phase 4 Study
• Brief Summary: The primary objective of this study is to evaluate the treatment benefit of erenumab on headache duration of at least moderate pain intensity.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Migraine

Intervention

• Drug: Erenumab
  140 mg, 2 consecutive injections of 70 mg
• Drug: Placebo
  2 consecutive injections

Study Arms

• Experimental: Erenumab

  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.
  Intervention: Drug: Erenumab
• Experimental: Placebo

  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.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 21, 2023): 512
• Original Estimated Enrollment (submitted: January 30, 2020): 576
• Actual Study Completion Date: October 26, 2023
• Actual Primary Completion Date: October 26, 2023 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Czechia, Hungary, Italy, Poland, Portugal, Romania, Spain, United States

Administrative Information

• NCT Number: NCT04252742
• Other Study ID Numbers: 20190008; 2019-003646-33 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s)and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• URL: https://www.amgen.com/datasharing

• Current Responsible Party: Amgen
• Original Responsible Party: Same as current
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: November 2023