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 | 19.0 |
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 AMG 334 compared to placebo on the proportion of patients with at least 50% reduction from baseline in monthly migraine days |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of AMG 334 compared to placebo on the change from baseline of monthly migraine days
To evaluate the effect of AMG 334 compared to placebo on the “impact on everyday activities” domain as measured by the MPFID
To evaluate the effect of AMG 334 compared to placebo on the “physical impairment” domain as measured by the Migraine Physical Function Impact Diary (MPFID)
To evaluate the effect of AMG 334 compared to placebo on change from baseline in monthly acute migraine-specific medication treatment days
To evaluate the effect of AMG 334 compared to placebo on the proportion of patients with at least 75% reduction from baseline in monthly migraine days
To evaluate the effect of AMG 334 compared to placebo on the proportion of patients with a 100% reduction from baseline in monthly migraine days
To evaluate the safety, tolerability, and immunogenicity of AMG 334 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Documented history of migraine (with or without aura) for ≥ 12 months prior to screening according to the International Classification of Headache Disorders, 3rd Edition (ICHD-3)
- 4 to 14 days per month of migraine symptoms (based on ICHD-3 criteria) on average across the 3 months prior to screening based on retrospective reporting
- <15 days per month of headache symptoms (ie migraine and non-migraine)
- Failed 2 to 4 prior migraine prophylaxis treatments out of the following: Propranolol/metoprolol, topiramate, flunarizine, valproate/divalproex, amitriptyline, venlafaxine, lisinopril, candesartan, locally approved products (e.g. oxeterone or pizotifen) |
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E.4 | Principal exclusion criteria |
- Older than 50 years of age at migraine onset
- Unable to differentiate migraine from other headaches
- History of cluster headache or hemiplegic migraine headache
- Failed more than 4 prior migraine prophylaxis treatments [as specified in protocol]
- Use of a prophylactic migraine medication within 5 half-lives, or a device or procedure within one month prior to the start of the baseline phase or during the baseline phase
- Prior Botulinum toxin A treatment in the head/neck region (including cosmetic use or other licensed indications for Botox ®) within 4 months prior to start of the baseline phase
- Use of the following for any indication in the 1 month prior to the start of the baseline phase or during the baseline phase:
o ergotamines or triptanes ≥10 days/month, or
o simple analgesics (NSAIDs, acetaminophen, paracetamol) ≥15 days/month, or
o opioid- or butalbital-containing analgesics ≥4 days/month |
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E.5 End points |
E.5.1 | Primary end point(s) |
Achievement of at least a 50% reduction from baseline in monthly migraine days in the last month (month 3) of the double-blind epoch |
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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 on monthly migraine days in the last month of the double-blind epoch
Change from baseline on MPFID/”impact on everyday activities” domain in the last month of the double-blind epoch
Change from baseline on MPFID/”physical impairment” domain in the last month of the double-blind epoch
Change from baseline of monthly acute migraine medication treatment days in the last month of the double-blind epoch
The achievement of at least a 75% reduction from baseline in monthly migraine days in the last month of the double-blind epoch
The achievement of at least a 100% reduction from baseline in monthly migraine days in the last month of the double-blind epoch.
Occurrence of cardiovascular events and evaluation of anti-drug antibodies in this patient population |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For full details, please refer to the schedule of assessments table in the protocol. |
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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 | Yes |
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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Antibody testing;
Further blood sampling for future biomarker development |
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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 | 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 | 2 |
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 | 76 |
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 |
Austria |
Belgium |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Italy |
Netherlands |
Norway |
Spain |
Sweden |
Switzerland |
United Kingdom |
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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
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |