Efficacy and Safety of Erenumab in Pediatric Subjects With Chronic Migraine
- Conditions
- Migraine
- Interventions
- Registration Number
- NCT03832998
- Lead Sponsor
- Amgen
- 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).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 284
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose Level 1 Erenumab Dose 2 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. Dose Level 1 Erenumab Dose 1 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. Dose Level 2 Erenumab Dose 3 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. Placebo Placebo - Dose Level 2 Erenumab Dose 2 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.
- Primary Outcome Measures
Name Time Method Change from baseline in MMDs Baseline through week 12 of DBTP 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.
- Secondary Outcome Measures
Name Time Method Number of participants experiencing Treatment-emergent Adverse Events (TEAE) Up to Week 83 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.
Number of participants expressing C Terminal Telopeptide of Type 1 Collagen (CTX) Markers Up to week 83 Change in monthly average severity of migraine attacks from baseline (measured with a visual analogue scale) Baseline through week 12 of the double blind treatment phase 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.
Number of participants expressing Procollagen Type 1 N Propeptide (P1NP) Markers Up to week 83 Change in monthly headache days from baseline Baseline through week 12 of the DBTP 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.
Proportion of participants with at least 50% reduction in MMDs from baseline Baseline through week 12 of the DBTP 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.
Change from baseline in migraine-related disability and productivity as assessed by the Pediatric Migraine Disability Assessment (PedMIDAS) Baseline through week 12 of the DBTP 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.
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 2 only: Number of participants experiencing injection site pain as assessed by FPS-R Day 1 and week 8 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 Change in MMDs from baseline to the average of the first 3 months Baseline through week 12 of the DBTP 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.
Number of participants expressing Anti-erenumab antibodies 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
Trial Locations
- Locations (101)
Paradigm Clinical Research Center Inc
🇺🇸San Diego, California, United States
Childrens Hospital Colorado
🇺🇸Aurora, Colorado, United States
Colorado Springs Neurological Associates
🇺🇸Colorado Springs, Colorado, United States
New England Institute for Clinical Research
🇺🇸Stamford, Connecticut, United States
Childrens National Health System
🇺🇸Washington, District of Columbia, United States
TrueBlue Clinical Research
🇺🇸Brandon, Florida, United States
Northwest Florida Clinical Research Group Limited Liability Company
🇺🇸Gulf Breeze, Florida, United States
Nicklaus Childrens Hospital
🇺🇸Miami, Florida, United States
Pediatric Epilepsy and Neurology Specialists
🇺🇸Tampa, Florida, United States
Premiere Research Institute
🇺🇸West Palm Beach, Florida, United States
Rare Disease Research Center Pediatrics
🇺🇸Atlanta, Georgia, United States
CenExel iResearch, LLC
🇺🇸Savannah, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Chicago Headache Center and Research Institute
🇺🇸Chicago, Illinois, United States
Josephson Wallack Munshower Neurology
🇺🇸Indianapolis, Indiana, United States
University of Maryland, Baltimore
🇺🇸Baltimore, Maryland, United States
New England Regional Headache Center Inc
🇺🇸Worcester, Massachusetts, United States
Michigan Head Pain and Neurological Institute
🇺🇸Ann Arbor, Michigan, United States
Clinical Research Institute Inc
🇺🇸Plymouth, Minnesota, United States
Childrens Mercy Hospital and Clinics
🇺🇸Kansas City, Missouri, United States
Mercy Research
🇺🇸Saint Louis, Missouri, United States
Meridian Clinical Research LLC
🇺🇸Hastings, Nebraska, United States
Dent Neurosciences Research Center
🇺🇸Amherst, New York, United States
Modern Migraine MD
🇺🇸New York, New York, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
Cincinnati Childrens Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Nationwide Childrens Hospital
🇺🇸Columbus, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Childrens Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Preferred Primary Care Physicians, Inc
🇺🇸Pittsburgh, Pennsylvania, United States
Palmetto Gastroenterology Clinical Research, LLC
🇺🇸Summerville, South Carolina, United States
Child Neurology Consultants of Austin
🇺🇸Austin, Texas, United States
Helios Clinical Research Inc
🇺🇸Burleson, Texas, United States
Stryde Consulting LLC
🇺🇸Frisco, Texas, United States
Childrens Specialty Group
🇺🇸Norfolk, Virginia, United States
Vaught Neurological Services
🇺🇸Crab Orchard, West Virginia, United States
Marshfield Clinic
🇺🇸Marshfield, Wisconsin, United States
Universitair Ziekenhuis Brussel
🇧🇪Brussel, Belgium
Algemeen Ziekenhuis Sint-Maarten
🇧🇪Mechelen, Belgium
Docteur Simona Sava
🇧🇪Saint Nicolas, Belgium
Stollery Childrens Hospital
🇨🇦Edmonton, Alberta, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Childrens Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
The Hospital For Sick Children
🇨🇦Toronto, Ontario, Canada
Fundacion Centro de Investigacion Clinica
🇨🇴Medellín, Antioquia, Colombia
Cafam
🇨🇴Bogota, Cundinamarca, Colombia
Fundacion Cardiovascular de Colombia
🇨🇴Bucaramanga, Santander, Colombia
Terveystalo Pulssi
🇫🇮Turku, Finland
Charite - Universitaetsmedizin Berlin, Campus Virchow
🇩🇪Berlin, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Schmerzklinik Kiel
🇩🇪Kiel, Germany
Arzneimittelforschung Leipzig GmbH
🇩🇪Leipzig, Germany
Dr Kenessey Albert Korhaz - Rendelointezet
🇭🇺Balassagyarmat, Hungary
Dr Altmann Anna egyeni vallalkozo
🇭🇺Budapest, Hungary
High Tech Medical Kft
🇭🇺Budapest, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Borsod-Abauj-Zemplen Varmegyei Kozponti Korhaz es Egyetemi Oktatokorhaz
🇭🇺Miskolc, Hungary
Fondazione IRCCS Istituto Neurologico Carlo Besta
🇮🇹Milano, Italy
Azienda di Rilievo Nazionale e Alta Specializzazione Civico Di Cristina Benfratelli
🇮🇹Palermo, Italy
Fondazione Istituto Neurologico Nazionale C Mondino IRCCS
🇮🇹Pavia, Italy
IRCCS Ospedale Pediatrico Bambino Gesu
🇮🇹Roma, Italy
Josai Kids Clinic
🇯🇵Nagoya-shi, Aichi, Japan
Medical Corporation Seikokai Takanoko Hospital
🇯🇵Matsuyama-shi, Ehime, Japan
Hiroshima City Hiroshima Citizens Hospital
🇯🇵Hiroshima-shi, Hiroshima, Japan
Kitami Clinic
🇯🇵Sapporo-shi, Hokkaido, Japan
Konan Medical Center
🇯🇵Kobe-shi, Hyogo, Japan
Kumamoto City Hospital
🇯🇵Kumamoto-shi, Kumamoto, Japan
Tatsuoka Neurology Clinic
🇯🇵Kyoto-shi, Kyoto, Japan
Japanese Red Cross Kyoto Daiichi Hospital
🇯🇵Kyoto-shi, Kyoto, Japan
Sendai Headache and Neurology Clinic
🇯🇵Sendai-shi, Miyagi, Japan
Tominaga Hospital
🇯🇵Osaka-shi, Osaka, Japan
Saitama Neuropsychiatric Institute
🇯🇵Saitama-shi, Saitama, Japan
Tokyo Headache Clinic
🇯🇵Shibuya-ku, Tokyo, Japan
Tokyo Medical University Hospital
🇯🇵Shinjuku-ku, Tokyo, Japan
Keio University Hospital
🇯🇵Shinjuku-ku, Tokyo, Japan
Nagamitsu Clinic
🇯🇵Hofu-shi, Yamaguchi, Japan
Nagaseki Headache Clinic
🇯🇵Kai-shi, Yamanashi, Japan
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Instytut Centrum Zdrowia Matki Polki
🇵🇱Lodz, Poland
Centrum Medyczne Luxmed Spzoo
🇵🇱Lublin, Poland
Centrum Medyczne Hope Clinic Sebastian Szklener
🇵🇱Lublin, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
🇵🇱Poznan, Poland
Clinical Research Center Spzoo Medic-R Spolka Komandytowa
🇵🇱Poznan, Poland
Dr Sekowska Leczenie Bolu
🇵🇱Warszawa, Poland
Next Stage Spzoo
🇵🇱Warszawa, Poland
Migre Polskie Centrum Leczenia Migreny Anna Gryglas-Dworak
🇵🇱Wroclaw, Poland
Puerto Rico Health and Wellness Institute
🇵🇷Dorado, Puerto Rico
FSBI Russian Children Clinical Hospital of the MoH RF
🇷🇺Moscow, Russian Federation
LLC clinic Chaika
🇷🇺Moscow, Russian Federation
LLC Sibneyromed
🇷🇺Novosibirsk, Russian Federation
LLC Medical Technologies
🇷🇺Saint Petersburg, Russian Federation
Noahs Ark Childrens Hospital for Wales
🇬🇧Cardiff, United Kingdom
Royal Hospital for Children
🇬🇧Glasgow, United Kingdom
4 Medical Clinical Solutions London
🇬🇧Ilford, United Kingdom
Alder Hey Childrens Hospital
🇬🇧Liverpool, United Kingdom
Evelina Childrens Hospital
🇬🇧London, United Kingdom
Great Ormond Street Hospital for Children
🇬🇧London, United Kingdom
4 Medical Clinical Solutions Manchester
🇬🇧Manchester, United Kingdom
Oxford Childrens Hospital
🇬🇧Oxford, United Kingdom