OASIS (CM): Efficacy and Safety of Erenumab in Pediatric Subjects With Chronic Migraine

Sponsor

Amgen (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03832998

Collaborator

Novartis (Industry)

286

Enrollment

Locations

Arms

87.7

Anticipated Duration (Months)

3.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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 subjects 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).

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: Erenumab Dose 1 Drug: Erenumab Dose 2 Drug: Erenumab Dose 3 Other: Placebo	Phase 3

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 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 286 participants (256 adolescents and 30 children).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

286 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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])

Actual Study Start Date :

Sep 5, 2019

Anticipated Primary Completion Date :

Aug 14, 2024

Anticipated Study Completion Date :

Dec 27, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Level 1 Subjects will be randomized to one of two doses determined by their body weight at Day 1.	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: AMG 334 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®
Experimental: Dose Level 2 Subjects will be randomized to one of two doses determined by their body weight at Day 1.	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®
Placebo Comparator: Placebo	Other: Placebo Placebo matching dose for erenumab dose 1, 2 and 3.

Arm

Intervention/Treatment

Experimental: Dose Level 1

Subjects will be randomized to one of two doses determined by their body weight at Day 1.

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:

AMG 334

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®

Experimental: Dose Level 2

Subjects will be randomized to one of two doses determined by their body weight at Day 1.

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®

Placebo Comparator: Placebo

Other: Placebo

Placebo matching dose for erenumab dose 1, 2 and 3.

Outcome Measures

Primary Outcome Measures

Change from baseline in monthly migraine days (MMDs) [Baseline through week 12 of the double blind treatment phase]
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).

Secondary Outcome Measures

Change in monthly headache days from baseline [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 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 [Baseline through week 12 of the double blind treatment phase]
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 [Baseline through week 12 of the double blind treatment phase]
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 months [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) [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 double-blind treatment period (DBTP). This will be measured in an electronic diary (eDiary) with a visual analogue scale.
Change from baseline in migraine-related disability and productivity [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 migraine-related disability and productivity as measured by the modified Pediatric Migraine Disability Assessment Questionnaire (modified PedMIDAS) to month 3 of the double-blind treatment period (DBTP).

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 ≥ 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 (subjects 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 subject 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 subject 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 subject is at risk of self-harm or harm to others.
History of major psychiatric disorder. Subjects with anxiety disorder and/or mild major depressive disorder (Patient Health Questionnaire Modified for Adolescents [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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital Colorado	Aurora	Colorado	United States	80045
2	Colorado Springs Neurological Associates	Colorado Springs	Colorado	United States	80907
3	New England Institute for Clinical Research	Stamford	Connecticut	United States	06905
4	Childrens National Health System	Washington	District of Columbia	United States	20010
5	Nicklaus Childrens Hospital	Miami	Florida	United States	33155
6	Premiere Research Institute	West Palm Beach	Florida	United States	33407
7	Ann and Robert H Lurie Childrens Hospital of Chicago	Chicago	Illinois	United States	60611
8	Josephson Wallack Munshower Neurology	Indianapolis	Indiana	United States	46256
9	University of Maryland, Baltimore	Baltimore	Maryland	United States	21201
10	New England Regional Headache Center Inc	Worcester	Massachusetts	United States	01605
11	Michigan Head Pain and Neurological Institute	Ann Arbor	Michigan	United States	48104
12	Clinical Research Institute Inc	Plymouth	Minnesota	United States	55441
13	Childrens Mercy Hospital and Clinics	Kansas City	Missouri	United States	64108
14	Mercy Research	Saint Louis	Missouri	United States	63141
15	Meridian Clinical Research LLC	Hastings	Nebraska	United States	68901
16	Dent Neurosciences Research Center	Amherst	New York	United States	14226
17	Columbia University Medical Center	New York	New York	United States	10032
18	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio	United States	45229
19	Cleveland Clinic	Cleveland	Ohio	United States	44195
20	Nationwide Childrens Hospital	Columbus	Ohio	United States	43205
21	Childrens Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
22	Preferred Primary Care Physicians, Inc	Pittsburgh	Pennsylvania	United States	15236
23	Childrens Specialty Group	Norfolk	Virginia	United States	23507
24	Vaught Neurological Services	Crab Orchard	West Virginia	United States	25827
25	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
26	Universitair Ziekenhuis Brussel	Brussel		Belgium	1090
27	Stollery Childrens Hospital	Edmonton	Alberta	Canada	T6G 1C9
28	London Health Sciences Centre	London	Ontario	Canada	N6A 4G5
29	Childrens Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
30	The Hospital For Sick Children	Toronto	Ontario	Canada	M5G 1X8
31	Fundacion Centro de Investigacion Clinica	Medellín	Antioquia	Colombia	050021
32	Solano y Terront Servicios Medicos Ltda - Unidad Integral de Endocrinologia Uniendo	Bogota	Cundinamarca	Colombia	110221
33	Cafam	Bogota	Cundinamarca	Colombia	111211
34	Fundacion Hospital Infantil Universitario De San Jose	Bogota	Cundinamarca	Colombia	111221
35	Fundacion Cardiovascular de Colombia	Floridablanca	Santander	Colombia	681004
36	Terveystalo Pulssi	Turku		Finland	20100
37	Charite Universitaetsmedizin Berlin Campus Virchow Klinikum	Berlin		Germany	13353
38	Universitaetsklinikum Essen	Essen		Germany	45147
39	Schmerzklinik Kiel	Kiel		Germany	24149
40	Arzneimittelforschung Leipzig GmbH	Leipzig		Germany	04107
41	Dr Kenessey Albert Korhaz - Rendelointezet	Balassagyarmat		Hungary	2660
42	Dr Altmann Anna egyeni vallalkozo	Budapest		Hungary	1026
43	Semmelweis Egyetem	Budapest		Hungary	1083
44	Debreceni Egyetem Klinikai Kozpont	Debrecen		Hungary	4032
45	Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz	Miskolc		Hungary	3526
46	Fondazione IRCCS Istituto Neurologico Carlo Besta	Milano		Italy	20133
47	Azienda ospedaliera di rilievo nazionale e di alta specializzazione Civico di Cristina Benfratelli	Palermo		Italy	90134
48	Fondazione Istituto Neurologico Nazionale C Mondino IRCCS	Pavia		Italy	27100
49	IRCCS Ospedale Pediatrico Bambino Gesu	Roma		Italy	00165
50	Josai Kids Clinic	Nagoya-shi	Aichi	Japan	451-0031
51	Hiroshima City Hiroshima Citizens Hospital	Hiroshima-shi	Hiroshima	Japan	730-8518
52	Kitami Clinic	Sapporo-shi	Hokkaido	Japan	060-0004
53	Konan Medical Center	Kobe-shi	Hyogo	Japan	658-0064
54	Kumamoto City Hospital	Kumamoto-shi	Kumamoto	Japan	862-8505
55	Tatsuoka Neurology Clinic	Kyoto-shi	Kyoto	Japan	600-8811
56	Sendai Headache and Neurology Clinic	Sendai-shi	Miyagi	Japan	982-0014
57	Tominaga Hospital	Osaka-shi	Osaka	Japan	556-0017
58	Saitama Neuropsychiatric Institute	Saitama-shi	Saitama	Japan	338-8577
59	Tokyo Headache Clinic	Shibuya-ku	Tokyo	Japan	151-0051
60	Tokyo Medical University Hospital	Shinjuku-ku	Tokyo	Japan	160-0023
61	Nagamitsu Clinic	Hofu-shi	Yamaguchi	Japan	747-0802
62	Nagaseki Headache Clinic	Kai-shi	Yamanashi	Japan	400-0124
63	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-952
64	Instytut Centrum Zdrowia Matki Polki	Lodz		Poland	93-338
65	Centrum Medyczne Luxmed Spzoo	Lublin		Poland	20-109
66	Szpital Kliniczny im Heliodora Swiecickiego Uniwersytetu Medycznego im Karola Marcinkowskiego w Pozn	Poznan		Poland	60-355
67	Clinical Research Center Spzoo Medic-R Spolka Komandytowa	Poznan		Poland	60-848
68	Dr Sekowska Leczenie Bolu	Warszawa		Poland	01-018
69	Next Stage	Warszawa		Poland	02-042
70	FSBI Russian Children Clinical Hospital of the MoH RF	Moscow		Russian Federation	119571
71	LLC clinic Chaika	Moscow		Russian Federation	125047
72	LLC Sibneyromed	Novosibirsk		Russian Federation	630004
73	LLC Medical Technologies	Saint Petersburg		Russian Federation	191025
74	Noahs Ark Childrens Hospital for Wales	Cardiff		United Kingdom	CF14 4XW
75	Royal Hospital for Children	Glasgow		United Kingdom	G51 4TF
76	Alder Hey Childrens Hospital	Liverpool		United Kingdom	L12 2AP
77	Evelina Childrens Hospital	London		United Kingdom	SE1 7EU
78	Great Ormond Street Hospital for Children	London		United Kingdom	WC1N 3JH
79	Oxford Childrens Hospital	Oxford		United Kingdom	OX3 9DU