E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027599 |
E.1.2 | Term | Migraine |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of erenumab compared with placebo on the change in monthly migraine days (MMDs) from baseline to week 9 through week 12 (month 3) of the double-blind treatment phase (DBTP).
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E.2.2 | Secondary objectives of the trial |
- To evaluate the effect of erenumab compared with placebo on the change in monthly headache days from baseline to week 9 through week 12 of the DBTP. - 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 of the DBTP. - To evaluate the effect of erenumab compared with placebo on change in MMDs from baseline to the average of the first 3 months of the DBTP. - To evaluate the effect of erenumab compared with placebo on change in monthly average severity of migraine attacks from baseline to week 9 through week 12 of the DBTP. - To evaluate the effect of erenumab compared with placebo on change in migraine-related disability and productivity as measured by the modified Pediatric Migraine Disability Assessment from baseline to week 9 through week 12 (month 3) of the DBTP |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
40-week optional dose-level-blinded extension phase (DLBEP), during which all subjects will receive erenumab at the blinded dose level. |
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E.3 | Principal inclusion criteria |
101 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. 102 Subject's parent or legal representative has provided written informed consent before initiation of any study-specific activities/procedures. 103 History of migraine (with or without aura) for ≥ 12 months before screening according to the IHS Classification ICHD-3 based on medical records and/or subject self-report or parents' or legal representative's report 104 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 105 Migraine frequency: ≥ 8 migraine days based on the eDiary data during the last 28 days of the baseline phase if > 28 days in duration. 106 Headache frequency of ≥ 15 headache days based on the eDiary data during the last 28 days of the baseline phase if > 28 days in duration. 107 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). |
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E.4 | Principal exclusion criteria |
201 History of cluster headache or hemiplegic migraine headache. 202 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 203 No therapeutic response with > 3 of the following 10 medication categories for prophylactic treatment of migraine after an adequate therapeutic trial. 204 Malignancy within 5 years before screening. 205 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 CSSRS assessed at screening. 206 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). 207 Human immunodeficiency virus (HIV) infection by history. 208 History of seizure disorder or other significant neurological disorder other than migraine. Note: a single childhood febrile seizure is not exclusionary. 209 History of major psychiatric disorder 210 Use of a prohibited medication within 15 days before the start of the baseline phase and/or during the baseline phase 211 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. 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). 212 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 213 Received medication targeting the CGRP pathway within 4 months before the start of the baseline phase or during the baseline phase 214 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: Opioid or butalbital-containing analgesics on ≥ 4 days per month. 215 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 216 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. 217 Hepatic disease by history or total bilirubin (TBL) ≥ 2.0 x upper limit of normal (ULN) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3.0 x ULN, as assessed by the central laboratory at initial screening. 218 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 or serum pregnancy test.) 219 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. Refer to Appendix 5 for additional contraceptive information. 220 Subject has known sensitivity to any of the products or components to be administered during dosing 221 Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments [COAs]) to the best of the subject's legal representative and investigator's knowledge. 222 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in MMDs to week 9 through week 12 (month 3) of the DBTP.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Change from baseline in monthly headache days to week 9 through week 12 (month 3) of the DBTP - Achievement of at least 50% reduction in MMDs from baseline to week 9 through week 12 (month 3) of the DBTP. - Change from baseline in MMDs to the average of the first 3 months (week 1 through week 12) of the DBTP. - Change from baseline in monthly average severity of migraine attacks to week 9 through week 12 (month 3) of the DBTP. - 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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Colombia |
Canada |
Japan |
Russian Federation |
United Kingdom |
United States |
Belgium |
Germany |
Hungary |
Italy |
Poland |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 8 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 8 |