Efficacy and Safety of Erenumab in Pediatric Subjects with Episodic Migraine

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

19 Jul 2019 → ongoing

Decision date (initial)

2024-07-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Amgen Inc.

External identifiers

EU CT number

2023-504930-23-00

EudraCT number

2017-002397-39

WHO UTN

U1111-1303-2374

ClinicalTrials.gov

NCT03836040

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the effect of erenumab compared with placebo on the change in monthly migraine days (MMD) from baseline to week 9 through week 12 (month 3) of the double-blind treatment phase (DBTP).

Secondary objectives 5

1. To evaluate the effect of erenumab compared with placebo on the change in monthly headache days from baseline to week 9 through week 12 (month 3) of the DBTP.
2. To evaluate the effect of erenumab compared with placebo on the proportion of subjects with at least 50% reduction in MMD from baseline to week 9 through week 12 (month 3) of the DBTP.
3. To evaluate the effect of erenumab compared with placebo on the change in MMD from baseline to the average of the first 3 months (week 1 through week 12) of the DBTP.
4. To evaluate the effect of erenumab compared with placebo on the change in monthly average severity of migraine attacks from baseline to week 9 through week 12 (month 3) of the DBTP.
5. To evaluate the effect of erenumab compared with placebo on the change in migraine related disability and productivity as measured by the modified Pediatric Migraine Disability Assessment (PedMIDAS) from baseline to week 9 through week 12 (month 3) of the DBTP.

Conditions and MedDRA coding

Episodic Migraine

Study design 2 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001664-PIP02-15

Plan to share IPD

Yes

IPD plan description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request. Information on IPD sharing Access Criteria, Time Frame and Supporting Information Type is available on ClinicalTrials.gov (NCT03836040) and on the Amgen Clinical Trials portal (http://www.amgen.com/datasharing).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 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.
2. Subject’s parent or legal epresentative has provided written informed consent before initiation of any study-specific activities/procedures.
3. 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
4. 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.
5. 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.
6. Headache frequency: < 15 headache days based on the eDiary data during the last 28 days of the baseline phase if ≥ 28 days in duration.
7. 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 16

1. History of cluster headache or hemiplegic migraine headache.
2. 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.
3. Malignancy within 5 years before screening.
4. 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.
5. 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).
6. Human immunodeficiency virus (HIV) infection by history.
7. History of seizure disorder or other significant neurological disorder other than migraine.
8. 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.
9. Use of prohibited medication within 15 days before the start of the baseline phase and/or during the baseline phase.
10. 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.
11. 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.
12. Received medication targeting the CGRP pathway within 4 months before the start of the baseline phase or during the baseline phase.
13. 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.
14. 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.
15. 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.
16. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in MMD to week 9 through week 12 (month 3) of the DBTP.

Secondary endpoints 5

1. Change from baseline in monthly headache days to week 9 through week 12 (month 3) of the DBTP.
2. Achievement of at least 50% reduction in MMD from baseline to week 9 through week 12 (month 3) of the DBTP
3. Change from baseline in MMD to the average of the first 3 months (week 1 through week 12) of the DBTP.
4. Change from baseline in monthly average severity of migraine attacks to week 9 through week 12 (month 3) of the DBTP.
5. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1799

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 6

Locations

7 EU/EEA countries · 28 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 226 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications