OASIS(EM): Efficacy and Safety of Erenumab in Pediatric Subjects With Episodic Migraine
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 episodic migraine. The study hypothesis is that in pediatric subjects 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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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 episodic 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 456 participants (376 adolescents and up to 80 children).
Study Design
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:
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:
|
| 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:
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:
|
| Placebo Comparator: Placebo Subjects will be randomized to a placebo comparator. |
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) [Completion of double blind treatment phase at 12 weeks]
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 [Completion of double blind treatment phase at 12 weeks]
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 [Completion of double blind treatment phase at 12 weeks]
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 [Completion of double blind treatment phase at 12 weeks]
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 month [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) [Completion of double blind treatment phase at 12 weeks]
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 a daily electronic diary (eDiary) with a visual analogue scale.
- Change from baseline in migraine-related disability and productivity [Completion of double blind treatment phase at 12 weeks]
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 (PedMIDAS) to month 3 of the double-blind treatment period (DBTP).
Eligibility Criteria
Criteria
-
Inclusion Criteria
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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.
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Subject's parent or legal representative has provided written informed consent before initiation of any study-specific activities/procedures.
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History of migraine (with or without aura) for greater than or equal to 12 months before screeningaccording to the IHS Classification ICHD-3 (Headache Classification Committeeof the International Headache Society, 2013) based on medical records and/or subject self-report or parents' or legal representative's report.
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The following ICHD-3 specifications for pediatric migraine (subjects aged less than 18 years), should be considered for the diagnosis of migraine:
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Attacks may last 2 to 72 hours.
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Migraine headache is more often bilateral than in adults; unilateral pain usually emerges in late adolescence or early adult life.
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Migraine headache is usually frontotemporal. Occipital headache in children is rare and calls for diagnostic caution.
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A subset of otherwise typical subjects have facial location of pain, which is called 'facial migraine' in the literature; there is no evidence that these subjects form a separate subgroup of migraine subjects.
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In young children, photophobia and phonophobia may be inferred from their behavior.
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History of less than 15 headache days per month of which greater than or equal to 4 headache days were assessed by the subject as migraine days in each of the 3 months prior to screening (refer to Section 5.6 for definition of migraine day)
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Criteria to be assessed prospectively during the 4-week baseline phase and confirmed before randomizing the subject into the DBTP:
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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
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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.
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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).
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Exclusion Criteria
• History of cluster headache or hemiplegic migraine headache.
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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:
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Category 1: beta blockers (eg, propranolol, atenolol, bisoprolol, metoprolol, nadolol, nebivolol, pindolol, timolol)
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Category 2: tricyclic antidepressants (eg, amitriptyline, nortriptyline, protriptyline)
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Category 3: topiramate
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Category 4: divalproex sodium, sodium valproate
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Category 5: serotonin-norepinephrine reuptake inhibitors (eg, venlafaxine, desvenlafaxine, duloxetine, milnacipran)
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Category 6: cyproheptadine
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Category 7: flunarizine, cinnarizine
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Category 8: botulinum toxin
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Category 9: lisinopril/candesartan
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Category 10: medications targeting the CGRP pathway
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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'sassessment.
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The following scenarios do not constitute lack of therapeutic response:
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Lack of sustained response to a medication.
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partial, suboptimal response to a medication
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failure to tolerate a therapeutic dose.
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Evidence of drug or alcohol abuse or dependence within 12 months before screening, based on medical records, subject self-report, or positive urine drug test performed during screening (with the exception of prescribed medications such as opioids or barbiturates).
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Human immunodeficiency virus (HIV) infection by history.
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History of seizure disorder or other significant neurological disorder other than migraine. Note: a single childhood febrile seizure is not exclusionary.
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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 basedon a patient health questionnaire-9 modified for adolescents (PHQ-A) score greater than or equal to 10 at screening. Subjects 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. Subjects must have been on a stable dose within the 3 months before the start of the baseline phase.
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Use of prohibited medication within 1 month before the start of the baseline phase and/or during the baseline phase
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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
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Subjects 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. Subjects 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: Subjects 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).
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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.
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Received medication targeting the CGRP pathway within 4 months before the start of the baseline phase or during the baseline phase.
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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:
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Ergotamines or triptans on greater than or equal 10 days per month.
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Simple analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs], acetaminophen) on greater than or equal 15 days per month.
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Opioid or butalbital-containing analgesics on greater than or equal 4 days per month.
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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.
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Subject has clinically significant vital signs, laboratory results, or ECG abnormality during screening that, in the opinion of the investigator, could pose a risk to subject safety or interfere with the study evaluation.
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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.
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Female subject 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.)
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Female subjects 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.
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Subject has known sensitivity to any of the products or components to be administered during dosing
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Subject 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 subject's legal representative and investigator's knowledge.
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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 subject safety or interfere with the study evaluation, procedures or completion.
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 | Minneapolis | Minnesota | United States | 55402 |
| 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 | Bucaramanga | Santander | Colombia | 681017 |
| 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 | Ishikawa Clinic | Kyoto-shi | Kyoto | Japan | 606-0851 |
| 57 | Sendai Headache and Neurology Clinic | Sendai-shi | Miyagi | Japan | 982-0014 |
| 58 | Tominaga Hospital | Osaka-shi | Osaka | Japan | 556-0017 |
| 59 | Saitama Neuropsychiatric Institute | Saitama-shi | Saitama | Japan | 338-8577 |
| 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 | Uniwersytecki Dzieciecy Szpital Kliniczny im Ludwika Zamenhofa w Bialymstoku | Bialystok | Poland | 15-274 | |
| 64 | AthleticoMed | Bydgoszcz | Poland | 85-752 | |
| 65 | Uniwersyteckie Centrum Kliniczne | Gdansk | Poland | 80-952 | |
| 66 | Instytut Centrum Zdrowia Matki Polki | Lodz | Poland | 93-338 | |
| 67 | Centrum Medyczne Luxmed Spzoo | Lublin | Poland | 20-109 | |
| 68 | Szpital Kliniczny im Heliodora Swiecickiego Uniwersytetu Medycznego im Karola Marcinkowskiego w Pozn | Poznan | Poland | 60-355 | |
| 69 | Clinical Research Center Spzoo Medic-R Spolka Komandytowa | Poznan | Poland | 60-848 | |
| 70 | Dr Sekowska Leczenie Bolu | Warszawa | Poland | 01-018 | |
| 71 | Next Stage | Warszawa | Poland | 02-042 | |
| 72 | FSBI Russian Children Clinical Hospital of the MoH RF | Moscow | Russian Federation | 119571 | |
| 73 | LLC clinic Chaika | Moscow | Russian Federation | 125047 | |
| 74 | LLC Sibneyromed | Novosibirsk | Russian Federation | 630004 | |
| 75 | LLC Medical Technologies | Saint Petersburg | Russian Federation | 191025 | |
| 76 | Universitaets-Kinderspital beider Basel | Basel | Switzerland | 4031 | |
| 77 | Kopfwehzentrum Hirslanden | Zollikon | Switzerland | 8702 | |
| 78 | Noahs Ark Childrens Hospital for Wales | Cardiff | United Kingdom | CF14 4XW | |
| 79 | Royal Hospital for Children | Glasgow | United Kingdom | G51 4TF | |
| 80 | Alder Hey Childrens Hospital | Liverpool | United Kingdom | L12 2AP | |
| 81 | Evelina Childrens Hospital | London | United Kingdom | SE1 7EU | |
| 82 | Great Ormond Street Hospital for Children | London | United Kingdom | WC1N 3JH | |
| 83 | Oxford Childrens Hospital | Oxford | United Kingdom | OX3 9DU |
Sponsors and Collaborators
- Amgen
- Novartis
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 20150125
- 2017-002397-39