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Efficacy and Safety of Erenumab in Pediatric Subjects With Episodic Migraine (OASIS(EM))

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ClinicalTrials.gov Identifier: NCT03836040
Recruitment Status : Recruiting
First Posted : February 11, 2019
Last Update Posted : January 4, 2022
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE January 29, 2019
First Posted Date  ICMJE February 11, 2019
Last Update Posted Date January 4, 2022
Actual Study Start Date  ICMJE July 19, 2019
Estimated Primary Completion Date August 14, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 7, 2019)
Change from baseline in monthly migraine days (MMDs) [ Time Frame: Completion of double blind treatment phase at 12 weeks ]
To evaluate the effect of erenumab compared with placebo on the change in MMDs from baseline to week 9 through week 12 (month 3) of the double-blind treatment period (DBTP).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2020)
  • Change in monthly headache days from baseline [ Time Frame: Completion of double blind treatment phase at 12 weeks ]
    To evaluate the effect of erenumab compared with placebo on the change from baseline in monthly headache days to week 9 through week 12 (month 3) of the double-blind treatment period (DBTP)
  • Proportion of subjects with at least 50% reduction in monthly migraine days (MMDs) from baseline [ Time Frame: Completion of double blind treatment phase at 12 weeks ]
    To evaluate the effect of erenumab compared with placebo on the proportion of subjects with at least 50% reduction in MMDs from baseline to week 9 through week 12 (month 3) of the double-blind treatment period (DBTP)
  • Change in monthly migraine days (MMDs) from baseline to the average of the first 3 months [ Time Frame: Completion of double blind treatment phase at 12 weeks ]
    To evaluate the effect of erenumab compared with placebo on the change in MMDs from baseline to the average of the first 3 months (week 1 through week 12) of the double-blind treatment period (DBTP).
  • Change in monthly migraine days (MMDs) from baseline to the average of the first 6 month [ Time Frame: Completion of double blind treatment phase at 24 weeks ]
    To evaluate the effect of erenumab compared with placebo on the change in MMDs from baseline to the average of the 6 month (week 1 through week 24) double-blind treatment period (DBTP).
  • Change in monthly average severity of migraine attacks from baseline (measured with a visual analogue scale) [ Time Frame: Completion of double blind treatment phase at 12 weeks ]
    To evaluate the effect of erenumab compared with placebo on the change from baseline in monthly average severity of migraine attacks to week 9 through week 12 (month 3) of the double-blind treatment period (DBTP). This will be measured in a daily electronic diary (eDiary) with a visual analogue scale.
  • Change from baseline in migraine-related disability and productivity [ Time Frame: Completion of double blind treatment phase at 12 weeks ]
    To evaluate the effect of erenumab compared with placebo on the change from baseline in migraine-related disability and productivity as measured by the modified Pediatric Migraine Disability Assessment Questionnaire (PedMIDAS) to month 3 of the double-blind treatment period (DBTP).
Original Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2019)
  • Change in monthly headache days from baseline [ Time Frame: Completion of double blind treatment phase at 12 weeks ]
    To evaluate the effect of erenumab compared with placebo on the change from baseline in monthly headache days to week 9 through week 12 (month 3) of the double-blind treatment period (DBTP)
  • Proportion of subjects with at least 50% reduction in monthly migraine days (MMDs) from baseline [ Time Frame: Completion of double blind treatment phase at 12 weeks ]
    To evaluate the effect of erenumab compared with placebo on the proportion of subjects with at least 50% reduction in MMDs from baseline to week 9 through week 12 (month 3) of the double-blind treatment period (DBTP
  • Change in monthly migraine days (MMDs) from baseline to the average of the first 3 months [ Time Frame: Completion of double blind treatment phase at 12 weeks ]
    To evaluate the effect of erenumab compared with placebo on the change in MMDs from baseline to the average of the first 3 months (week 1 through week 12) of the double-blind treatment period (DBTP).
  • Change in monthly migraine days (MMDs) from baseline to the average of the first 6 month [ Time Frame: Completion of double blind treatment phase at 24 weeks ]
    To evaluate the effect of erenumab compared with placebo on the change in MMDs from baseline to the average of the 6 month (week 1 through week 24) double-blind treatment period (DBTP).
  • Change in monthly average severity of migraine attacks from baseline (measured with a visual analogue scale) [ Time Frame: Completion of double blind treatment phase at 12 weeks ]
    To evaluate the effect of erenumab compared with placebo on the change from baseline in monthly average severity of migraine attacks to week 9 through week 12 (month 3) of the double-blind treatment period (DBTP). This will be measured in a daily electronic diary (eDiary) with a visual analogue scale.
  • Change from baseline in migraine-related disability and productivity [ Time Frame: Completion of double blind treatment phase at 12 weeks ]
    To evaluate the effect of erenumab compared with placebo on the change from baseline in migraine-related disability and productivity as measured by the modified Pediatric Migraine Disability Assessment Questionnaire (PedMIDAS) to month 3 of the double-blind treatment period (DBTP).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Erenumab in Pediatric Subjects With Episodic Migraine
Official Title  ICMJE A Phase 3, Randomized, Double-blind,Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Erenumab in Children (6 to < 12 Years) and Adolescents (12 to < 18 Years) With Episodic Migraine (OASIS PEDIATRIC [EM])
Brief Summary This study will evaluate the efficacy and safety of erenumab in migraine prevention in children (6 to <12 years) and adolescents (12 to <18 years) with episodic migraine. The study hypothesis is that in pediatric subjects with episodic migraine, the combined erenumab dose group has a greater reduction from baseline to week 9 through week 12 (month 3) in monthly migraine days (MMDs) when compared with placebo in the double-blind treatment phase (DBTP).
Detailed Description

This study is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of erenumab in migraine prevention in children (6 to <12 years) and adolescents (12 to <18 years) with episodic migraine.

The trial consists of four phases: screening (up to 3 weeks of initial screening and a 4-week prospective baseline phase); the double-blind treatment phase (24 weeks) in which participants receive placebo or Erenumab dose 1, dose 2 or dose 3 (based on participant's body weight) via subcutaneous injection once a month; the optional dose level blinded extension phase (40 weeks), in which all participants are assigned to receive dose 1, dose 2 or dose 3 of Erenumab; and a 12 weeks safety follow-up phase (16 weeks after the last dose of investigational drug).

The study intends to enroll 456 participants (376 adolescents and up to 80 children).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Migraine
Intervention  ICMJE
  • Drug: Erenumab Dose 1
    Subjects in the low body-weight group at day 1 and who are randomized to Dose Level 1 will receive this dose.
    Other Names:
    • AMG334
    • Aimovig®
  • Drug: Erenumab Dose 2
    Subjects in the low body-weight group at day 1 who are randomized to Dose Level 2 and subjects in the high body-weight group at day 1 who are randomized to Dose Level 1 will receive this dose.
    Other Names:
    • AMG 334
    • Aimovig®
  • Drug: Erenumab Dose 3
    Subjects in the high body-weight group at day 1 who are randomized to Dose Level 2 will receive this dose.
    Other Names:
    • AMG 334
    • Aimovig®
  • Other: Placebo
    Placebo matching dose for erenumab dose 1, 2 and 3.
Study Arms  ICMJE
  • Experimental: Dose level 1
    Subjects will be randomized to one of two doses determined by their body weight at Day 1.
    Interventions:
    • Drug: Erenumab Dose 1
    • Drug: Erenumab Dose 2
  • Experimental: Dose level 2
    Subjects will be randomized to one of two doses determined by their body weight at Day 1.
    Interventions:
    • Drug: Erenumab Dose 2
    • Drug: Erenumab Dose 3
  • Placebo Comparator: Placebo
    Subjects will be randomized to a placebo comparator.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 7, 2019)
456
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 25, 2026
Estimated Primary Completion Date August 14, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • Inclusion Criteria

    • Children (6 to less than 12 years of age) or adolescent (12 to less than 18 years of age) at the time of signing, if developmentally appropriate, the formal assent to participate to the study.
    • Subject's parent or legal representative has provided written informed consent before initiation of any study-specific activities/procedures.
    • History of migraine (with or without aura) for greater than or equal to 12 months before screeningaccording to the IHS Classification ICHD-3 (Headache Classification Committeeof the International Headache Society, 2013) based on medical records and/or subject self-report or parents' or legal representative's report.
    • The following ICHD-3 specifications for pediatric migraine (subjects aged less than 18 years), should be considered for the diagnosis of migraine:
    • Attacks may last 2 to 72 hours.
    • Migraine headache is more often bilateral than in adults; unilateral pain usually emerges in late adolescence or early adult life.
    • Migraine headache is usually frontotemporal. Occipital headache in children is rare and calls for diagnostic caution.
    • A subset of otherwise typical subjects have facial location of pain, which is called 'facial migraine' in the literature; there is no evidence that these subjects form a separate subgroup of migraine subjects.
    • In young children, photophobia and phonophobia may be inferred from their behavior.
    • History of less than 15 headache days per month of which greater than or equal to 4 headache days were assessed by the subject as migraine days in each of the 3 months prior to screening (refer to Section 5.6 for definition of migraine day)
  • Criteria to be assessed prospectively during the 4-week baseline phase and confirmed before randomizing the subject into the DBTP:

    • Migraine frequency: greater than or equal 4 and less than 15 migraine days based on the eDiary data during the last 28 days of the baseline phase if greater than 28 days in duration
    • Headache frequency: less than 15 headache days based on the eDiary data during the last 28 days of the baseline phase if greater than 28 days in duration.
    • Demonstrated at least 80% compliance with the eDiary based on the last 28 days of the baseline period, if greater than 28 days in duration (eg, completing eDiary items for at least 23 out of the last 28 days of the baseline phase).
  • Exclusion Criteria

    • History of cluster headache or hemiplegic migraine headache.

  • No therapeutic response with greater than 2 of the following 10 medication categories for prophylactic treatment of migraine after an adequate therapeutic trial. These medication categories are:

    • Category 1: beta blockers (eg, propranolol, atenolol, bisoprolol, metoprolol, nadolol, nebivolol, pindolol, timolol)
    • Category 2: tricyclic antidepressants (eg, amitriptyline, nortriptyline, protriptyline)
    • Category 3: topiramate
    • Category 4: divalproex sodium, sodium valproate
    • Category 5: serotonin-norepinephrine reuptake inhibitors (eg, venlafaxine, desvenlafaxine, duloxetine, milnacipran)
    • Category 6: cyproheptadine
    • Category 7: flunarizine, cinnarizine
    • Category 8: botulinum toxin
    • Category 9: lisinopril/candesartan
    • Category 10: medications targeting the CGRP pathway
  • No therapeutic response is defined as no reduction in headache frequency, duration, or severity after administration of the medication for at least 6 weeks at the generally-accepted therapeutic dose(s) based on the investigator'sassessment.
  • The following scenarios do not constitute lack of therapeutic response:

    • Lack of sustained response to a medication.
    • partial, suboptimal response to a medication
    • failure to tolerate a therapeutic dose.
    • Evidence of drug or alcohol abuse or dependence within 12 months before screening, based on medical records, subject self-report, or positive urine drug test performed during screening (with the exception of prescribed medications such as opioids or barbiturates).
    • Human immunodeficiency virus (HIV) infection by history.
    • History of seizure disorder or other significant neurological disorder other than migraine. Note: a single childhood febrile seizure is not exclusionary.
    • History of major psychiatric disorder (such as schizophrenia, schizoaffective disorder, bipolar disorder, obsessive-compulsive disorder, or pervasive developmental disorder), or current evidence of major depressive disorder basedon a patient health questionnaire-9 modified for adolescents (PHQ-A) score greater than or equal to 10 at screening. Subjects with anxiety disorder and/or mild major depressive disorder (with PHQ-A score ≤ 9) are permitted in the study if they are considered by the investigator to be stable and are taking no more than 1 medication for each disorder. Subjects must have been on a stable dose within the 3 months before the start of the baseline phase.
    • Use of prohibited medication within 1 month before the start of the baseline phase and/or during the baseline phase
    • Use of prohibited devices (such as stimulation devices) or procedures (such as acupuncture, biofeedback, relaxation techniques, or psychotherapy) with the goal of preventing migraines, within 3 months before the start of the baseline phase and/or during the baseline phase
    • Subjects receiving Cognitive Behavioral Therapy (CBT) are excluded unless they are on a stable, maintenance phase of a CBT program for migraine for at least 3 months before the start of the baseline phase. Subjects undergoing CBT are considered on a stable, maintenance phase if they have undergone greater than or equal 6 weekly or biweekly sessions of CBT administered by adequately trained psychologists and who, for at least 3 months before the start of the baseline phase, only follow "booster" CBT sessions at a monthly, bimonthly or quarterly frequency. Note: Subjects who have discontinued CBT within 3 months prior to the start of the baseline phase are eligible for the study provided that there is evidence of CBT failure/lack of efficacy prior to initial screening (per medical records or investigator's assessment).
    • Received botulinum toxin in the head and/or neck region within 4 months before the start of the baseline phase or during the baseline phase.
    • Received medication targeting the CGRP pathway within 4 months before the start of the baseline phase or during the baseline phase.
  • Taken the following for any indication in any month during the 2 months before the start of the baseline phase, or during the baseline phase:

    • Ergotamines or triptans on greater than or equal 10 days per month.
    • Simple analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs], acetaminophen) on greater than or equal 15 days per month.
    • Opioid or butalbital-containing analgesics on greater than or equal 4 days per month.
    • Currently receiving treatment in another investigational device or drug study, or less than 90 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
    • Subject has clinically significant vital signs, laboratory results, or ECG abnormality during screening that, in the opinion of the investigator, could pose a risk to subject safety or interfere with the study evaluation.
    • Hepatic disease by history or total bilirubin (TBL) greater than or equal 2.0 x upper limit of normal (ULN) or alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than or equal 3.0 x ULN, as assessed by the central laboratory at initial screening.
    • Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during the study and for an additional 16 weeks after the last dose of investigational product. (Females of childbearing potential should only be included in the study after a confirmed menstrual period and a negative highly sensitive urine and serum pregnancy test.)
    • Female subjects of childbearing potential unwilling to use an acceptable method of effective contraception during treatment and for an additional 16 weeks after the last dose of investigational product.
    • Subject has known sensitivity to any of the products or components to be administered during dosing
    • Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject's legal representative and investigator's knowledge.
    • History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com
Listed Location Countries  ICMJE Belgium,   Canada,   Colombia,   Finland,   Germany,   Hungary,   Italy,   Japan,   Poland,   Russian Federation,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03836040
Other Study ID Numbers  ICMJE 20150125
2017-002397-39 ( EudraCT Number )
Has Data Monitoring Committee Yes
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  ICMJE
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 URL below.
URL: https://www.amgen.com/datasharing
Responsible Party Amgen
Study Sponsor  ICMJE Amgen
Collaborators  ICMJE Novartis
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP