| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 |
|
| 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 achieving medication overuse headache (MOH) remission during the double-blind treatment period (DBTP) |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the effect of erenumab compared with placebo in reducing AHMD during the DBTP
- To evaluate the effect of erenumab compared with placebo on sustaining MOH remission during the DBTP
- To evaluate the effect of erenumab compared with placebo on reducing the impact of migraines on physical impairment and
everyday activities as measured by the Migraine Physical Function Impact Diary (MPFID) during the DBTPa
- • To evaluate the effect of erenumab compared to placebo on change from baseline in headache impact scores as measured by the
Headache Impact Test (HIT-6)a |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
101 Subject has provided informed consent prior to initiation of any study-specific activities/procedures
102 Age ≥ 18 years on entry into the study
103 Documented history of migraine without aura and/or migraine with aura according to the ICHD-3 Classification for ≥ 12 months at screening
104 Documented history of CM for a minimal duration of 6 months before screening
105 Current diagnosis of MOH
106 History of treatment failure with at least 1 preventive treatment as defined as treatment discontinuation due to lack of efficacy, adverse event or general poor tolerability
107. ≥ 14 headache days during the 28-day baseline period out of which ≥ 8 headache days meet criteria as migraine days
108 Observation of acute migraine medication overuse during baseline. Medication overuse at baseline is defined as:
- ≥ 10 days of combination treatment OR
- ≥ 10 days of short-acting opioids/opioid-containing medication OR
- ≥ 10 days of triptans, ergots, OR
- ≥ 15 days of NSAIDs or simple analgesics intake
110 At least 2 acute headache medication days per week for each week with at least 5 diary days
111 Demonstrated at least 80% compliance with the eDiary (eg, must complete eDiary items on at least 23 out of 28 days during the baseline phase) |
|
| E.4 | Principal exclusion criteria |
201 Age > 50 years at migraine onset or > 65 years at CM onset
202 History of hemiplegic migraine, cluster headache or other trigeminal autonomic cephalalgia
203 Current concomitant diagnosis of a secondary type of headache other than MOH
204 History of clinically significant orofacial pain (eg, painful cranial neuropathies, temporomandibular disorder) that in the opinion of the investigator or Amgen's physician, if consulted, could interfere with the study evaluation, procedures or completion
205 Chronic headache with continuous pain, in which the subject does not experience headache-free periods of any duration
206 No therapeutic response in prevention of migraine after an adequate therapeutic trial of > 3 of the following medication categories. These medication categories include:
- Category 1: Topiramate
- Category 2: Other antiepileptics (eg, divalproex sodium, sodium
valproate, carbamazepine)
- Category 3: Beta blockers
- Category 4: Tricyclic antidepressants
- Category 5: Serotonin-norepinephrine reuptake inhibitors, selective
serotonin-reuptake inhibitors and other antidepressants
- Category 6: Calcium channel blockers (eg, verapamil, amlodipine) or
calcium antagonists (eg, flunarizine)
- Category 7: Angiotensin receptor blockers (eg, candesartan) or
angiotensin-converting enzyme (ACE) inhibitors (eg, lisinopril)
- Category 8: Botulinum toxin
- Category 9: Other centrally acting drugs used for migraine prophylaxis (eg, pizotifen)
235. Changes in drug regimen (ie, changes in dose or frequency of use) of an allowed migraine preventive medication within 2 months prior to start of baseline
208 Received botulinum toxin in the head and/or neck region within 4 months prior to screening
236. Documented history of treatment with an anti-CGRP preventive treatment
210 Anticipated to require any excluded medication/device or procedure during the study
211 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 and investigator's knowledge
212 History or evidence of unstable or clinically significant medical condition that, in the opinion of the investigator or Amgen's physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or
completion. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Absence of MOH at month 6 as defined by mean monthly acute headache medication days (AHMD) < 10 days over months 4, 5, and 6 (week 12 through 24) OR mean monthly headache days (MHD) < 14 days over months 4, 5, and 6 (week 12 through 24) of the DBTP where
AHMD include any eDiary day in which an acute headache medication intake is reported |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Months 4,5 and 6 (week 12 through 24) |
|
| E.5.2 | Secondary end point(s) |
- Change from baseline in mean monthly AHMD over months 4, 5,
and 6 (week 13 through 24) of the DBTP
- Sustained MOH remission during DBTP, as defined by absence of MOH at months 3 (week 12) and 6 (week 24) of the DBTP, and
“absence of MOH” is achieved when mean monthly AHMD < 10 days OR mean MHD < 14 days over the respective 3-month period
- Change from baseline in mean monthly average physical impairment domain scores as measured by the MPFID over months 4, 5, and 6 (week 13 through 24) of the DBTP
- Change from baseline in mean monthly average impact on everyday activities domain scores as measured by the MPFID over months 4, 5, and 6 (week 13 through 24) of the DBTP
- Change from baseline in mean HIT-6 score over months 4, 5, and 6 (week 13 through 24) of the DBTP |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Months 4,5 and 6 (week 12 through 24) |
|
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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 | Yes |
| 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 | 3 |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 55 |
| 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 |
| Australia |
| Canada |
| Japan |
| United Kingdom |
| United States |
| Austria |
| Czechia |
| Finland |
| France |
| Hungary |
| Italy |
| Poland |
| Portugal |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
Print
