Efficacy and Safety of Erenumab in Pediatric Subjects With Chronic Migraine

Study Overview
=================
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 chronic migraine. The study hypothesis is that in pediatric participants with chronic 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 chronic migraine. The trial consists of four phases: screening (up to 3 weeks of initial screening and a 4-week prospective baseline phase); the DBTP (24 weeks for Group 1 subjects; 12-weeks for Group 2 subjects) 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 enrol 286 participants (256 adolescents and 30 children).

Official Title
-----------------
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 Chronic Migraine (OASIS PEDIATRIC [CM])

Conditions
-----------------
Migraine

Intervention / Treatment
-----------------
* Drug: Erenumab Dose 1
* Drug: Erenumab Dose 2
* Drug: Erenumab Dose 3
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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. Participant'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 ≥ 12 months before screening according to the IHS Classification ICHD-3 (Headache Classification Committee of the International Headache Society, 2013) ICHD-3 specifications for pediatric migraine (participants aged less than 18 years), should be considered for the diagnosis of migraine. History of ≥ 15 headache days per month of which ≥ 8 headache days were assessed by the participant as migraine days per month in each of the 3 months prior to screening. Migraine frequency: greater than or equal to 8 migraine days based on the eDiary data during the last 28 days of the baseline phase if more than 28 days in duration. Headache frequency of greater than or equal to 15 headache days based on the eDiary data during the last 28 days of the baseline phase if more than 28 days in duration. Demonstrated at least 80% compliance with the eDiary based on the last 28 days of the baseline period, if more than 28 days in duration (eg, completing eDiary items for at least 23 out of the last 28 days of the baseline phase). Key Exclusion Criteria: History of cluster headache or hemiplegic migraine headache. Chronic migraine with continuous pain, in which the participant does not have any pain free periods (of any duration) during the 1 month prior to screening. No therapeutic response with greater than 3 medication categories for prophylactic treatment of migraine after an adequate therapeutic trial. 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's assessment. History of suicidal behavior or the participant is at risk of self-harm or harm to others. History of major psychiatric disorder. Participants with anxiety disorder and/or mild major depressive disorder (Patient Health Questionnaire Modified for Adolescents [PHQ-A] score 9 for adolescents or based on medical judgement of the investigator for children) 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. Participants must have been on a stable dose within the 3 months before the start of the baseline phase.

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Level 1<br>Participants will be randomized to one of two doses determined by their body weight at Day 1. Participants who enrolled under the original protocol or protocol amendment 1 will be identified as group 1. Those enrolled under protocol amendment 2 will be identified as group 2. | Drug: Erenumab Dose 1<br>* Participants in the low body-weight group at day 1 and who are randomized to Dose Level 1 will receive this dose.<br>* Other names: Aimovig®;Drug: Erenumab Dose 2<br>* Participants in the low body-weight group at day 1 who are randomized to Dose Level 2 and participants in the high body-weight group at day 1 who are randomized to Dose Level 1 will receive this dose.<br>* Other names: Aimovig®;|
| Experimental: Dose Level 2<br>Participants will be randomized to one of two doses determined by their body-weight at Day 1. Participants who enrolled under the original protocol or protocol amendment 1 will be identified as group 1. Those enrolled under protocol amendment 2 will be identified as group 2. | Drug: Erenumab Dose 2<br>* Participants in the low body-weight group at day 1 who are randomized to Dose Level 2 and participants in the high body-weight group at day 1 who are randomized to Dose Level 1 will receive this dose.<br>* Other names: Aimovig®;Drug: Erenumab Dose 3<br>* Participants in the high body-weight group at day 1 who are randomized to Dose Level 2 will receive this dose.<br>* Other names: Aimovig®;|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo matching dose for erenumab dose 1, 2 and 3.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in MMDs | 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 DBTP. | Baseline through week 12 of DBTP | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in monthly headache days from baseline | 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 DBTP. | Baseline through week 12 of the DBTP | 
| Proportion of participants with at least 50% reduction in MMDs from baseline | To evaluate the effect of erenumab compared with placebo on the proportion of participants with at least 50% reduction in MMDs from baseline to week 9 through week 12 (month 3) of the DBTP. | Baseline through week 12 of the DBTP | 
| Change in MMDs from baseline to the average of the first 3 months | 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 DBTP. | Baseline through week 12 of the DBTP | 
| Change in monthly average severity of migraine attacks from baseline (measured with a visual analogue scale) | 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 DBTP. This will be measured in an electronic diary (eDiary) with a visual analogue scale. | Baseline through week 12 of the double blind treatment phase | 
| Change from baseline in migraine-related disability and productivity as assessed by the Pediatric Migraine Disability Assessment (PedMIDAS) | 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 PedMIDAS to week 9 through week 12 (month 3) of the DBTP. | Baseline through week 12 of the DBTP | 
| Number of participants experiencing Treatment-emergent Adverse Events (TEAE) | TEAEs are any event that occurred after the participant received study treatment. Any clinically significant changes in vital signs, electrocardiograms, and clinical laboratory tests that occurred after study treatment administration were recorded as TEAEs. A serious TEAE is any untoward medical occurrence in a clinical study participant after first dose irrespective of a causal relationship with the study treatment(s) that resulted in death, was immediately life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or another medically important serious event. | Up to Week 83 | 
| Number of participants expressing C Terminal Telopeptide of Type 1 Collagen (CTX) Markers |  | Up to week 83 | 
| Number of participants expressing Procollagen Type 1 N Propeptide (P1NP) Markers |  | Up to week 83 | 
| Number of participants expressing Anti-erenumab antibodies |  | Up to week 83 | 
| Change in growth and development rate as assessed by physical measuraments based on age-adjusted Z-scores for height and weight |  | Up to week 83 | 
| Number of participants experiencing treatment-emergent suicidal ideation and behavior as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS). |  | Up to week 83 | 
| Group 1 only: Number of participants experiencing injection site pain as assessed by Face Pain Scale-revised (FPS-R) |  | Day 1 and week 20 | 
| Group 2 only: Number of participants experiencing injection site pain as assessed by FPS-R |  | Day 1 and week 8 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Migraine, Headache, Prevention, Pediatric, Chronic Migraine