Clinical trial NCT03836040: Efficacy and Safety of Erenumab in Pediatric Participants With Episodic Migraine
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 Episodic Migraine (OASIS PEDIATRIC [EM])
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Migraine
Keywords: Migraine
Headache
Prevention
Pediatric
Episodic Migraine
Lead sponsor: Amgen
Sponsor class: INDUSTRY
Collaborators: name: Novartis
First posted: 2019-02-11
Enrollment: 456
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 participants 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 DBTP (24 weeks for Group 1 participants; 12-weeks for Group 2 participants) 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).

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 greater than or equal to 12 months before screening according to the IHS Classification ICHD-3 (Headache Classification Committee of the International Headache Society, 2013) based on medical records and/or participant self-report or parents' or legal representative's report.
  * The following ICHD-3 specifications for pediatric migraine (participants 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 participants have facial location of pain, which is called 'facial migraine' in the literature; there is no evidence that these participants form a separate subgroup of migraine participants.
  * 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 participant 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 participant 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's assessment.
* 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, participant 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 based on a patient health questionnaire-9 modified for adolescents (PHQ-A) score greater than or equal to 10 at screening. Participants 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. Participant 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.
  * Participants 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. Participants 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: Participants 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.
  * Participant has clinically significant vital signs, laboratory results, or ECG abnormality during screening that, in the opinion of the investigator, could pose a risk to participant 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 participant 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 participants 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.
  * Participant has known sensitivity to any of the products or components to be administered during dosing.
  * Participant 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 participant'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 participant safety or interfere with the study evaluation, procedures or completion.

Primary outcomes:
measure: Change from baseline in MMDs
timeFrame: Baseline through week 12 of the double blind treatment phase
Secondary outcomes:
measure: Change in monthly headache days from baseline
timeFrame: Baseline through week 12 of the double blind treatment phase
measure: Proportion of participants with at least 50% reduction in MMDs from baseline
timeFrame: Baseline through week 12 of the double blind treatment phase
measure: Change in MMDs from baseline to the average of the first 3 months
timeFrame: Baseline through week 12 of the double blind treatment phase
measure: Change in monthly average severity of migraine attacks from baseline (measured with a visual analogue scale)
timeFrame: Baseline through week 12 of the double blind treatment phase
measure: Change from baseline in migraine-related disability and productivity
timeFrame: Baseline through week 12 of the double blind treatment phase
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Paradigm Clinical Research Center Inc
state: California
city: Aurora
country: United States
facility: Childrens Hospital Colorado
state: Colorado
city: Colorado Springs
country: United States
facility: Colorado Springs Neurological Associates
state: Colorado
city: Stamford
country: United States
facility: New England Institute for Clinical Research
state: Connecticut
city: Washington
country: United States
facility: Childrens National Health System
state: District of Columbia
city: Gulf Breeze
country: United States
facility: Northwest Florida Clinical Research Group Limited Liability Company
state: Florida
city: Miami
country: United States
facility: Nicklaus Childrens Hospital
state: Florida
city: Miami
country: United States
facility: Nicklaus Childrens Hospital
state: Florida
city: Tampa
country: United States
facility: Pediatric Epilepsy and Neurology Specialists
state: Florida
city: Tampa
country: United States
facility: TrueBlue Clinical Research
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research Center Pediatrics
state: Georgia
city: Savannah
country: United States
facility: CenExel iResearch, LLC
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Chicago Headache Center and Research Institute
state: Illinois
city: Indianapolis
country: United States
facility: Josephson Wallack Munshower Neurology
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland, Baltimore
state: Maryland
city: Worcester
country: United States
facility: New England Regional Headache Center Inc
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Head Pain and Neurological Institute
state: Michigan
city: Minneapolis
country: United States
facility: Clinical Research Institute Inc
state: Minnesota
city: Kansas City
country: United States
facility: Childrens Mercy Hospital and Clinics
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Research
state: Missouri
city: Grand Island
country: United States
facility: Velocity Clinical Research, Inc
state: Nebraska
city: Amherst
country: United States
facility: Dent Neurosciences Research Center
state: New York
city: New York
country: United States
facility: Modern Migraine MD
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Nationwide Childrens Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Childrens Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians, Inc
state: Pennsylvania
city: Summerville
country: United States
facility: Palmetto Gastroenterology Clinical Research, LLC
state: South Carolina
city: Austin
country: United States
facility: Child Neurology Consultants of Austin
state: Texas
city: Burleson
country: United States
facility: Helios Clinical Research Inc
state: Texas
city: Frisco
country: United States
facility: Stryde Consulting LLC
state: Texas
city: Norfolk
country: United States
facility: Childrens Specialty Group
state: Virginia
city: Crab Orchard
country: United States
facility: Vaught Neurological Services
state: West Virginia
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Brussel
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Mechelen
country: Belgium
facility: Algemeen Ziekenhuis Sint-Maarten
city: Saint Nicolas
country: Belgium
facility: Docteur Simona Sava
city: Edmonton
country: Canada
facility: Stollery Childrens Hospital
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Childrens Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: The Hospital For Sick Children
state: Ontario
city: Medellin
country: Colombia
facility: Servicios de Salud Ips Suramericana Sas - Ips Sura Industriales
state: Antioquia
city: Medellín
country: Colombia
facility: Fundacion Centro de Investigacion Clinica
state: Antioquia
city: Rionegro
country: Colombia
facility: Institucion Prestadora de Servicios de Salud Sociedad Médica Rionegro SA Somer SA
state: Antioquia
city: Bogota
country: Colombia
facility: Solano y Terront Servicios Medicos SAS - Unidad Integral de Endocrinologia Uniendo
state: Cundinamarca
city: Bogota
country: Colombia
facility: Cafam
state: Cundinamarca
city: Bogota
country: Colombia
facility: Fundacion Hospital Infantil Universitario De San Jose
state: Cundinamarca
city: Bucaramanga
country: Colombia
facility: Fundacion cardiovascular de Colombia
state: Santander
city: Turku
country: Finland
facility: Terveystalo Pulssi
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin, Campus Virchow
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Greifswald
country: Germany
facility: Universitaetsklinikum Greifswald
city: Kiel
country: Germany
facility: Schmerzklinik Kiel
city: Leipzig
country: Germany
facility: Arzneimittelforschung Leipzig GmbH
city: Balassagyarmat
country: Hungary
facility: Dr Kenessey Albert Korhaz - Rendelointezet
city: Budapest
country: Hungary
facility: Dr Altmann Anna egyeni vallalkozo
city: Budapest
country: Hungary
facility: High Tech Medical Kft
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen Varmegyei Kozponti Korhaz es Egyetemi Oktatokorhaz
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Palermo
country: Italy
facility: Azienda di Rilievo Nazionale e Alta Specializzazione Civico Di Cristina Benfratelli
city: Pavia
country: Italy
facility: Fondazione Istituto Neurologico Nazionale C Mondino IRCCS
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu
city: Nagoya-shi
country: Japan
facility: Josai Kids Clinic
state: Aichi
city: Matsuyama-shi
country: Japan
facility: Medical Corporation Seikokai Takanoko Hospital
state: Ehime
city: Hiroshima-shi
country: Japan
facility: Hiroshima City Hiroshima Citizens Hospital
state: Hiroshima
city: Sapporo-shi
country: Japan
facility: Kitami Clinic
state: Hokkaido
city: Kobe-shi
country: Japan
facility: Konan Medical Center
state: Hyogo
city: Kochi-shi
country: Japan
facility: Umenotsuji Clinic
state: Kochi
city: Kumamoto-shi
country: Japan
facility: Kumamoto City Hospital
state: Kumamoto
city: Kyoto-shi
country: Japan
facility: Tatsuoka Neurology Clinic
state: Kyoto
city: Kyoto-shi
country: Japan
facility: Japanese Red Cross Kyoto Daiichi Hospital
state: Kyoto
city: Kyoto-shi
country: Japan
facility: Ishikawa Clinic
state: Kyoto
city: Sendai-shi
country: Japan
facility: Sendai Headache and Neurology Clinic
state: Miyagi
city: Osaka-shi
country: Japan
facility: Tominaga Hospital
state: Osaka
city: Saitama-shi
country: Japan
facility: Saitama Neuropsychiatric Institute
state: Saitama
city: Shinjuku-ku
country: Japan
facility: Tokyo Medical University Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Hofu-shi
country: Japan
facility: Nagamitsu Clinic
state: Yamaguchi
city: Kai-shi
country: Japan
facility: Nagaseki Headache Clinic
state: Yamanashi
city: Bialystok
country: Poland
facility: Uniwersytecki Dzieciecy Szpital Kliniczny im Ludwika Zamenhofa w Bialymstoku
city: Bydgoszcz
country: Poland
facility: AthleticoMed
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Lublin
country: Poland
facility: Centrum Medyczne Luxmed Spzoo
city: Lublin
country: Poland
facility: Centrum Medyczne Hope Clinic Sebastian Szklener
city: Poznan
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
city: Poznan
country: Poland
facility: Clinical Research Center Spzoo Medic-R Spolka Komandytowa
city: Warszawa
country: Poland
facility: Dr Sekowska Leczenie Bolu
city: Warszawa
country: Poland
facility: Next Stage Spzoo
city: Wroclaw
country: Poland
facility: Migre Polskie Centrum Leczenia Migreny Anna Gryglas-Dworak
city: Coimbra
country: Portugal
facility: Unidade Local de Saude de Coimbra, EPE - Hospital Pediatrico de Coimbra
city: Lisboa
country: Portugal
facility: Unidade Local de Saude de Sao Jose, EPE - Hospital Dona Estefania
city: Lisboa
country: Portugal
facility: Hospital da Luz, SA
city: Lisboa
country: Portugal
facility: Unidade Local de Saude de Santa Maria, EPE - Hospital de Santa Maria
city: Dorado
country: Puerto Rico
facility: Puerto Rico Health and Wellness Institute
city: Moscow
country: Russian Federation
facility: FSBI Russian Children Clinical Hospital of the MoH RF
city: Moscow
country: Russian Federation
facility: LLC clinic Chaika
city: Novosibirsk
country: Russian Federation
facility: LLC Sibneyromed
city: Saint Petersburg
country: Russian Federation
facility: LLC Medical Technologies
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Andalucía
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
state: Cataluña
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
state: Comunidad Valenciana
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Basel
country: Switzerland
facility: Universitaets-Kinderspital beider Basel
city: Zollikon
country: Switzerland
facility: Kopfwehzentrum Hirslanden
city: Cardiff
country: United Kingdom
facility: Noahs Ark Childrens Hospital for Wales
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Children
city: Liverpool
country: United Kingdom
facility: Alder Hey Childrens Hospital
city: London
country: United Kingdom
facility: Evelina Childrens Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
city: Manchester
country: United Kingdom
facility: 4 Medical Clinical Solutions Manchester
city: Oxford
country: United Kingdom
facility: Oxford Childrens Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: