ERENUMAB for Episodic migraine

Stratification factors

• body weight group

Inclusion criteria

• {"criterion_text":"- Children (6 to < 12 years of age) or adolescent (12 to < 18 years of age) at the time of signing, if developmentally appropriate, the formal assent to participate to the study."}
• {"criterion_text":"- Subject’s parent or legal epresentative has provided written informed consent before initiation of any study-specific activities/procedures."}
• {"criterion_text":"- 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) 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 < 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"}
• {"criterion_text":"- History of < 15 headache days per month of which ≥ 4 headache days were assessed by the subject as migraine days in each of the 3 months prior to screening."}
• {"criterion_text":"- Migraine frequency: ≥ 4 and < 15 migraine days based on the eDiary data during the last 28 days of the baseline phase if ≥28 days in duration."}
• {"criterion_text":"- Headache frequency: < 15 headache days based on the eDiary data during the last 28 days of the baseline phase if ≥ 28 days in duration."}
• {"criterion_text":"- Demonstrated at least 80% compliance with the eDiary based on the last 28 days of the baseline period, if ≥28 days in duration (eg, completing eDiary items for at least 23 out of the last 28 days of the baseline phase)."}

Exclusion criteria

• {"criterion_text":"- History of cluster headache or hemiplegic migraine headache."}
• {"criterion_text":"- 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 ≥ 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Received medication targeting the CGRP pathway within 4 months before the start of the baseline phase or during the baseline phase."}
• {"criterion_text":"- 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 ≥ 10 days per month. Simple analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs], acetaminophen) on ≥ 15 days per month. Opioid or butalbital-containing analgesics on ≥ 4 days per month."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Hepatic disease by history or total bilirubin (TBL) ≥ 2.0 x upper limit of normal (ULN) or alanine transaminase (ALT) or aspartate aminotransferase (AST) ≥ 3.0 x ULN, as assessed by the central laboratory at initial screening."}
• {"criterion_text":"- No therapeutic response with > 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 Category 2: tricyclic antidepressants Category 3: topiramate Category 4: divalproex sodium, sodium valproate Category 5: serotonin-norepinephrine reuptake inhibitors 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."}
• {"criterion_text":"- Malignancy within 5 years before screening."}
• {"criterion_text":"- History of suicidal behavior or the subject is at risk of self-harm or harm to others as evidenced by endorsement of items 4 or 5 on the pediatric Columbia-suicide Severity Rating Scale (C-SSRS) assessed at screening."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Human immunodeficiency virus (HIV) infection by history."}
• {"criterion_text":"- History of seizure disorder or other significant neurological disorder other than migraine."}
• {"criterion_text":"- 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 ≥ 10 at screening for adolescents or based on medical judgement of the investigator for children. Subjects with anxiety disorder and/or mild major depressive disorder (with PHQ-A score ≤ 9 for adolescents or based on medical judgement of the investigator for children) 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."}
• {"criterion_text":"- Use of prohibited medication within 15 days before the start of the baseline phase and/or during the baseline phase."}

Primary endpoints

• {"endpoint_text":"- Change from baseline in MMD to week 9 through week 12 (month 3) of the DBTP.","definition_or_measurement_approach":"Change in monthly migraine days (MMD) from baseline to week 9 through week 12 of the double-blind treatment phase (DBTP); MMD and headache days are recorded using the eDiary per protocol."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in monthly headache days to week 9 through week 12 (month 3) of the DBTP.","definition_or_measurement_approach":"Change in monthly headache days measured from eDiary data from baseline to week 9 through week 12 of DBTP."}
• {"endpoint_text":"- Achievement of at least 50% reduction in MMD from baseline to week 9 through week 12 (month 3) of the DBTP","definition_or_measurement_approach":"Proportion of subjects with ≥50% reduction in monthly migraine days (MMD) from baseline to week 9 through week 12 of DBTP, based on eDiary."}
• {"endpoint_text":"- Change from baseline in MMD to the average of the first 3 months (week 1 through week 12) of the DBTP.","definition_or_measurement_approach":"Change in monthly migraine days averaged over week 1 through week 12 of DBTP, using eDiary-recorded migraine days."}
• {"endpoint_text":"- Change from baseline in monthly average severity of migraine attacks to week 9 through week 12 (month 3) of the DBTP.","definition_or_measurement_approach":"Monthly average severity of migraine attacks compared from baseline to week 9 through week 12 of DBTP; severity assessed per protocol (patient-reported measures recorded via eDiary/eCOA)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Change in disability/productivity measured by the modified Pediatric Migraine Disability Assessment (PedMIDAS) from baseline to week 9 through week 12 of DBTP."}

Methods

• Site-based recruitment via neurology and pediatric neurology clinics (country-specific site lists and local referral channels).
• Recruitment materials: patient leaflets, patient visit guides, posters for sites, physician/GP referral letters and animations (documents K1/K2 in multiple countries).
• Pre-screening and screening data collection supported by Reify Health (onestudyteam) as indicated in sponsor third-party duties.

Germany

Earliest CTIS Part Ii Submission Date

03-05-2024

Latest Decision Or Authorization Date

10-10-2025

Processing Time Days

525

Number Of Sites

3

Number Of Participants

20

Hungary

Earliest CTIS Part Ii Submission Date

03-05-2024

Latest Decision Or Authorization Date

15-10-2025

Processing Time Days

530

Number Of Sites

3

Number Of Participants

56

Portugal

Earliest CTIS Part Ii Submission Date

03-05-2024

Latest Decision Or Authorization Date

10-10-2025

Processing Time Days

525

Number Of Sites

4

Number Of Participants

14

Spain

Earliest CTIS Part Ii Submission Date

03-05-2024

Latest Decision Or Authorization Date

13-10-2025

Processing Time Days

528

Number Of Sites

5

Number Of Participants

17

Belgium

Earliest CTIS Part Ii Submission Date

03-05-2024

Latest Decision Or Authorization Date

13-10-2025

Processing Time Days

528

Number Of Sites

3

Number Of Participants

9

Italy

Earliest CTIS Part Ii Submission Date

03-05-2024

Latest Decision Or Authorization Date

16-10-2025

Processing Time Days

531

Number Of Sites

2

Number Of Participants

30

Poland

Earliest CTIS Part Ii Submission Date

03-05-2024

Latest Decision Or Authorization Date

13-10-2025

Processing Time Days

528

Number Of Sites

8

Number Of Participants

87

Primary sponsor

Full Name

Amgen Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Syngene International Limited

Responsibilities

PK and ADA analysis

Name

Q Squared Solutions Limited

Responsibilities

eClinical/laboratory services (sponsor duties code 4)

Name

Perceptive Eclinical Limited

Responsibilities

eClinical services (sponsor duties code 3)

Name

Reify Health Inc.

Responsibilities

Pre-screening and screening data collection

Name

Eresearchtechnology Inc.

Responsibilities

ECG analysis / review and regulatory support

Third parties

• {"country":"India","full_name":"Syngene International Limited","duties_or_roles":"PK and ADA analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Sponsor third-party duties (code 4) (laboratory/vendor services)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Perceptive Eclinical Limited","duties_or_roles":"Sponsor third-party duties (code 3) (eClinical services)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Reify Health Inc.","duties_or_roles":"Pre-screening and screening data collection","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG analysis / review; regulatory/other duties","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Regulatory affairs / additional sponsor duties","organisation_type":"Pharmaceutical company"}