Efficacy and Safety of Erenumab in Pediatric Subjects With Episodic Migraine

JRCT ID: jRCT2080225072

Registered date:14/02/2020

Basic Information

• Recruitment status: recruiting
• Health condition(s) or Problem(s) studied: Migraine
• Date of first enrollment: 19/07/2019
• Target sample size: 456
• Countries of recruitment: United States,Belgium,Canada,Colombia,Finland,Germany,Hungary,Italy,Poland,Portugal,Puerto Rico,Russian Federation,Spain,Switzerland,United Kingdom
• Study type: Interventional

Intervention(s)

investigational material(s)
Generic name etc : Erenumab
INN of investigational material : Erenumab
Therapeutic category code : 119 Other agents affecting central nervous system
Dosage and Administration for Investigational material : Weight-based injections of erenumab Dose 1 or Dose 2 will be administered subcutaneously monthly during the 24 week double-blind phase.

control material(s)
Generic name etc :
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : Placebo will be administered subcutaneously monthly during the 24 week double-blind treatment period.

Outcome(s)

Primary Outcome

efficacy1.Change from baseline in monthly migraine days (MMDs) [ Time Frame: 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

efficacy
1. Change in monthly headache days from baseline [ Time Frame: 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)
2. Proportion of subjects with at least 50% reduction in monthly migraine days (MMDs) from baseline [ Time Frame: 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)
3. Change in monthly migraine days (MMDs) from baseline to the average of the first 3 months [ Time Frame: 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).
4. Change in monthly migraine days (MMDs) from baseline to the average of the first 6 month [ Time Frame: 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).
5. Change in monthly average severity of migraine attacks from baseline (measured with a visual analogue scale) [ Time Frame: 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.
6. Change from baseline in migraine-related disability and productivity [ Time Frame: 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).

Key inclusion & exclusion criteria

• Age minimum: >= 6age old
• Age maximum: <= 17age old
• Gender: Both

Include criteria

1. 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.
2. Subject's parent or legal representative has provided written informed consent before initiation of any study specific activities/procedures.
3. 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 subject self-report or parents' or legal representative's report.
The following ICHD-3 specifications for pediatric migraine (subjects 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 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.
- In young children, photophobia and phonophobia may be inferred from their behavior.
4. 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.
Criteria to be assessed prospectively during the 4-week baseline phase and confirmed before randomizing the subject into the DBTP:
5. Migraine frequency: greater than or equal to 4 and less than 15 migraine days based on the eDiary data during the last 28 days of the baseline if greater than 28 days in duration.
6. 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.
7. 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).

Exclude criteria

1. History of cluster headache or hemiplegic migraine headache.
2. 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.
3. 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).
4. Human immunodeficiency virus (HIV) infection by history
5. History of seizure disorder or other significant neurological disorder other than migraine. Note: a single childhood febrile seizure is not exclusionary.
6. 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. 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.
7. Use of prohibited medication within 1 month before the start of the baseline phase and/or during the baseline phase
8. 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
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).
9. Received botulinum toxin in the head and/or neck region within 4months before the start of the baseline phase or during the baseline phase.
10. Received medication targeting the CGRP pathway within 4 months before the start of the baseline phase or during the baseline phase.
11. 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 4days per month.
12. 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.
13. 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.
14. Hepatic disease by history or total bilirubin (TBL) greater than or equal2.0 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.
15. 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.)
16. 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.
17. Subject has known sensitivity to any of the products or components to be administered during dosing
18. 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.
19. 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.

Related Information

• Primary Sponsor: Amgen K.K.
• Secondary ID(s): NCT03836040,JapicCTI-205167