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 | 18.0 |
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 change from baseline in mean monthly migraine days, in subjects with episodic migraine |
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E.2.2 | Secondary objectives of the trial |
Efficacy:
• To evaluate the effect of AMG 334 compared to placebo on the proportion of subjects with at least 50% reduction from baseline in mean monthly migraine days
• To evaluate the effect of AMG 334 compared to placebo on the change from baseline in mean monthly acute migraine-specific medication treatment days
• To evaluate the effect of AMG 334 compared to placebo on the change from baseline in physical impairment as measured by the Migraine Physical Function Impact Diary (MPFID)
• To evaluate the effect of AMG 334 compared to placebo on the change from baseline in impact on everyday activities as measured by the MPFID
Safety: To evaluate the safety and tolerability of AMG 334 |
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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 |
Pharmacokinetic sub-study |
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E.3 | Principal inclusion criteria |
Criteria to be assessed prior to entering the subject into the initial screening phase and/or baseline phase:
•Adults ≥ 18 to ≤ 65 years of age upon entry into screening
•History of migraine (with or without aura) for ≥ 12 months prior to screening according to the IHS Classification ICHD-3 based on medical records and/or patient self-report
• Migraine frequency: ≥ 4 and < 15 migraine days per month on average across the 3 months prior to screening
• Headache (ie, migraine and non-migraine headache) frequency: < 15 headache days per month on average across the 3 months prior to screening
Criteria to be assessed during the baseline phase and confirmed prior to randomizing the subject into the double-blind treatment phase:
• Migraine frequency: ≥ 4 and < 15 migraine days during the baseline phase based on the eDiary calculations
• Headache frequency: < 15 headache days during the baseline phase based on the eDiary calculations
• Demonstrated at least 80% compliance with the eDiary |
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E.4 | Principal exclusion criteria |
• Older than 50 years of age at migraine onset
• History of cluster headache or hemiplegic migraine headache
• Unable to differentiate migraine from other headaches
• No therapeutic response with > 2 of the following 7 medication categories for prophylactic treatment of migraine after an adequate therapeutic trial. These medication categories are:
- Category 1: Divalproex sodium, sodium valproate
- Category 2: Topiramate
- Category 3: Beta blockers
- Category 4: Tricyclic antidepressants
- Category 5: Serotonin-norepinephrine reuptake inhibitors
- Category 6: Flunarizine, verapamil
- Category 7: Lisinopril, candesartan
• Used a prohibited medication, device, or procedure within 2 months prior to the start of the baseline phase or during the baseline phase
• Received botulinum toxin in the head and/or neck region within 4 months prior to the start of the baseline phase or during the baseline phase
• Taken the following for any indication in any month during the 2 months prior to the start of the baseline phase:
- Ergotamines or triptans on ≥ 10 days per month, or
- Simple analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs], acetaminophen) on ≥ 15 days per month, or
- Opioid- or butalbital-containing analgesics on ≥ 4 days per month
• Anticipated to require any excluded medication, device, or procedure during the study
• Active chronic pain syndromes (such as fibromyalgia and chronic pelvic pain)
• History of major psychiatric disorder (such as schizophrenia and bipolar disorder), or current evidence of depression based on a Beck Depression Inventory (BDI)-II total score > 19 at screening. Subjects with anxiety disorder and/or major depressive disorder 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 prior to the start of the baseline phase.
• History of seizure disorder or other significant neurological conditions other than migraine. Note: A single childhood febrile seizure is not exclusionary.
• Malignancy within the 5 years prior to screening, except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ
• Human immunodeficiency virus (HIV) infection by history
• Hepatic disease by history or total bilirubin ≥ 2.0 x ULN or alanine transaminase (ALT) or aspartate aminotransferase (AST) ≥ 3.0 x ULN, as assessed by the central laboratory at initial screening
• Myocardial infarction (MI), stroke, transient ischemic attack (TIA), unstable angina, or coronary artery bypass surgery or other revascularization procedure within 12 months prior to screening
• History or evidence of any other unstable or clinically significant medical condition, that in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
• Subject has any clinically significant vital sign, laboratory, 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
• The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior or endorsing items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) assessed at screening
• Evidence of drug or alcohol abuse or dependence within 12 months prior to screening, based on medical records, patient self-report, or positive urine drug test performed during screening (with the exception of prescribed medications such as opioids or barbiturates)
• Pregnant or breastfeeding, or is a female expecting to conceive during the study, including through 16 weeks after the last dose of investigational product
• Female subject of childbearing potential who is unwilling to use an acceptable method of effective contraception during treatment with investigational product through 16 weeks after the last dose of investigational product.
• Currently receiving treatment in another investigational device or drug study, or less than 90 days prior to screening since ending treatment on another investigational device or drug study(-ies)
• Known sensitivity to any component of the investigational product
• Previously randomized into an AMG 334 study
• Member of investigational site staff or relative of the investigator
• Unlikely to be able to complete all protocol required study visits or procedures, and/or to comply with all required study procedures (eg, independent completion of electronic diary [eDiary] items) to the best of the subject’s and investigator’s knowledge |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in mean monthly migraine days. The mean monthly migraine days will be calculated using the monthly migraine days from each of the last three months (months 4, 5, and 6) of the double-blind treatment phase. |
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E.5.1.1 | 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.5.2 | Secondary end point(s) |
Efficacy:
• Achievement of at least a 50% reduction from baseline in mean monthly migraine days over the last three months (months 4, 5, and 6) of the double-blind treatment phase
• Change from baseline in mean monthly acute migraine-specific medication treatment days over the last three months (months 4, 5, and 6) of the double-blind treatment phase
• Change from baseline in physical impairment over the last three months (months 4, 5, and 6) of the double-blind treatment phase as measured by the Migraine Physical Function Impact Diary (MPFID)
• Change from baseline in impact on everyday activities over the last three months (months 4, 5, and 6) of the double-blind treatment phase as measured by the MPFID
Safety:
• Adverse events
• Clinical laboratory values and vital signs
• Anti-AMG 334 antibodies |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 77 |
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 |
Austria |
Belgium |
Bulgaria |
Canada |
Czech Republic |
Finland |
Germany |
Hungary |
Netherlands |
Poland |
Slovakia |
Sweden |
Turkey |
United Kingdom |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 18 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 18 |