Efficacy and Safety of Erenumab in Pediatric Participants With Episodic Migraine

Migraine Clinical Trial

— OASIS(EM)  

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])

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03836040
• Other study ID #: 20150125
• Secondary ID: 2023-504930-23
• Status: Recruiting
• Phase: Phase 3
• Start date: July 19, 2019
• Est. completion date: May 5, 2027

Study information

• Verified date: June 2024
• Source: Amgen
• Contact: Amgen Call Center
• Phone: 866-572-6436
• Email: medinfo[@]amgen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 456
• Est. completion date: May 5, 2027
• Est. primary completion date: May 6, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

• 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.

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

Intervention

Drug:
• Erenumab Dose 1
Participants in the low body-weight group at day 1 and who are randomized to Dose Level 1 will receive this dose.
• Erenumab Dose 2
Participants 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.
• Erenumab Dose 3
Participants in the high body-weight group at day 1 who are randomized to Dose Level 2 will receive this dose.

Other:
• Placebo
Placebo matching dose for erenumab dose 1, 2 and 3.

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Brussel	Brussel
Belgium	Algemeen Ziekenhuis Sint-Maarten	Mechelen
Belgium	Docteur Simona Sava	Saint Nicolas
Canada	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
Colombia	Cafam	Bogota	Cundinamarca
Colombia	Fundacion Hospital Infantil Universitario De San Jose	Bogota	Cundinamarca
Colombia	Solano y Terront Servicios Medicos SAS - Unidad Integral de Endocrinologia Uniendo	Bogota	Cundinamarca
Colombia	Fundacion Cardiovascular de Colombia	Bucaramanga	Santander
Colombia	Fundacion Centro de Investigacion Clinica	Medellín	Antioquia
Finland	Terveystalo Pulssi	Turku
Germany	Charite - Universitaetsmedizin Berlin, Campus Virchow	Berlin
Germany	Universitaetsklinikum Essen	Essen
Germany	Schmerzklinik Kiel	Kiel
Germany	Arzneimittelforschung Leipzig GmbH	Leipzig
Hungary	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
Italy	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
Japan	Hiroshima City Hiroshima Citizens Hospital	Hiroshima-shi	Hiroshima
Japan	Nagamitsu Clinic	Hofu-shi	Yamaguchi
Japan	Nagaseki Headache Clinic	Kai-shi	Yamanashi
Japan	Konan Medical Center	Kobe-shi	Hyogo
Japan	Kumamoto City Hospital	Kumamoto-shi	Kumamoto
Japan	Ishikawa Clinic	Kyoto-shi	Kyoto
Japan	Japanese Red Cross Kyoto Daiichi Hospital	Kyoto-shi	Kyoto
Japan	Tatsuoka Neurology Clinic	Kyoto-shi	Kyoto
Japan	Medical Corporation Seikokai Takanoko Hospital	Matsuyama-shi	Ehime
Japan	Josai Kids Clinic	Nagoya-shi	Aichi
Japan	Tominaga Hospital	Osaka-shi	Osaka
Japan	Saitama Neuropsychiatric Institute	Saitama-shi	Saitama
Japan	Kitami Clinic	Sapporo-shi	Hokkaido
Japan	Sendai Headache and Neurology Clinic	Sendai-shi	Miyagi
Japan	Keio University Hospital	Shinjuku-ku	Tokyo
Japan	Tokyo Medical University Hospital	Shinjuku-ku	Tokyo
Poland	Uniwersytecki Dzieciecy Szpital Kliniczny im Ludwika Zamenhofa w Bialymstoku	Bialystok
Poland	AthleticoMed	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Instytut Centrum Zdrowia Matki Polki	Lodz
Poland	Centrum Medyczne Hope Clinic Sebastian Szklener	Lublin
Poland	Centrum Medyczne Luxmed Spzoo	Lublin
Poland	Clinical Research Center Spzoo Medic-R Spolka Komandytowa	Poznan
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu	Poznan
Poland	Dr Sekowska Leczenie Bolu	Warszawa
Poland	Next Stage Spzoo	Warszawa
Poland	Migre Polskie Centrum Leczenia Migreny Anna Gryglas-Dworak	Wroclaw
Portugal	Unidade Local de Saude de Coimbra, EPE - Hospital Pediatrico de Coimbra	Coimbra
Portugal	Hospital da Luz, SA	Lisboa
Portugal	Unidade Local de Saude de Santa Maria, EPE - Hospital de Santa Maria	Lisboa
Portugal	Unidade Local de Saude de Sao Jose, EPE - Hospital Dona Estefania	Lisboa
Puerto Rico	Puerto Rico Health and Wellness Institute	Dorado
Russian Federation	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
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona	Cataluña
Spain	Hospital Universitari Vall d Hebron	Barcelona	Cataluña
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Universitario Virgen del Rocio	Sevilla	Andalucía
Spain	Hospital Universitari i Politecnic La Fe	Valencia	Comunidad Valenciana
Switzerland	Universitaets-Kinderspital beider Basel	Basel
Switzerland	Kopfwehzentrum Hirslanden	Zollikon
United Kingdom	Noahs Ark Childrens Hospital for Wales	Cardiff
United Kingdom	Royal Hospital for Children	Glasgow
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 States	Dent Neurosciences Research Center	Amherst	New York
United States	Michigan Head Pain and Neurological Institute	Ann Arbor	Michigan
United States	Rare Disease Research Center Pediatrics	Atlanta	Georgia
United States	Childrens Hospital Colorado	Aurora	Colorado
United States	University of Maryland, Baltimore	Baltimore	Maryland
United States	TrueBlue Clinical Research	Brandon	Florida
United States	Helios Clinical Research Inc	Burleson	Texas
United States	Ann and Robert H Lurie Childrens Hospital of Chicago	Chicago	Illinois
United States	Chicago Headache Center and Research Institute	Chicago	Illinois
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Colorado Springs Neurological Associates	Colorado Springs	Colorado
United States	Nationwide Childrens Hospital	Columbus	Ohio
United States	Vaught Neurological Services	Crab Orchard	West Virginia
United States	Stryde Consulting LLC	Frisco	Texas
United States	Northwest Florida Clinical Research Group Limited Liability Company	Gulf Breeze	Florida
United States	Meridian Clinical Research LLC	Hastings	Nebraska
United States	Josephson Wallack Munshower Neurology	Indianapolis	Indiana
United States	Childrens Mercy Hospital and Clinics	Kansas City	Missouri
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Nicklaus Childrens Hospital	Miami	Florida
United States	Nicklaus Childrens Hospital	Miami	Florida
United States	Clinical Research Institute Inc	Minneapolis	Minnesota
United States	Columbia University Medical Center	New York	New York
United States	Modern Migraine MD	New York	New York
United States	Childrens Specialty Group	Norfolk	Virginia
United States	Childrens Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Preferred Primary Care Physicians, Inc	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Mercy Research	Saint Louis	Missouri
United States	Paradigm Clinical Research Center Inc	San Diego	California
United States	CenExel iResearch, LLC	Savannah	Georgia
United States	New England Institute for Clinical Research	Stamford	Connecticut
United States	Palmetto Gastroenterology Clinical Research, LLC	Summerville	South Carolina
United States	Childrens National Health System	Washington	District of Columbia
United States	Premiere Research Institute	West Palm Beach	Florida
United States	New England Regional Headache Center Inc	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Amgen	Novartis

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Colombia,  Finland,  Germany,  Hungary,  Italy,  Japan,  Poland,  Portugal,  Puerto Rico,  Russian Federation,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 the double-blind treatment period (DBTP).	Baseline through week 12 of the double blind treatment phase
Secondary	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 the DBTP	Baseline through week 12 of the double blind treatment phase
Secondary	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 double blind treatment phase
Secondary	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 double blind treatment phase
Secondary	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 a daily electronic diary (eDiary) with a visual analogue scale.	Baseline through week 12 of the double blind treatment phase
Secondary	Change from baseline in migraine-related disability and productivity	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 double blind treatment phase

External Links

•   AmgenTrials clinical trials website