E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of chronic migraine |
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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 | LLT |
E.1.2 | Classification code | 10027608 |
E.1.2 | Term | Migraine, unspecified |
E.1.2 | System Organ Class | 100000004852 |
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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 monthly migraine days, in subjects with chronic 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 monthly migraine days, in subjects with
chronic migraine
• To evaluate the effect of AMG 334, compared to placebo, as measured by the change from baseline on monthly migraine-specific medication treatment usage
• To evaluate the effect of AMG 334 compared to placebo as measured
by change from baseline on monthly cumulative hours of headache
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 |
There is an optional Pharmacokinetic (PK) Substudy.
Subjects may also elect to participate in a Novel Patient-reported Outcome Substudy. |
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E.3 | Principal inclusion criteria |
- Adults ≥ 18 to ≤ 65 years of age upon entry into screening
- History of at least 5 attacks of migraine without aura and/or migraine with visual,
sensory, speech and/or language, retinal or brainstem aura according to the IHS Classification ICHD-III (Headache Classification Committee of the International
Headache Society, 2013) based on medical records and/or patient self-report
- 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
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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
- Chronic migraine with continuous pain, in which the subject does not experience any pain free periods (of any duration) during the 1 month prior to screening
- Taken an opioid and/or opioid-containing analgesic for any indication on greater than 12 days during the 3 months prior to screening
- Taken a butalbital-containing analgesic for any indication on greater than 6 days during the 3 months prior to screening
- No therapeutic response in prophylaxis of migraine after an adequate therapeutic trial to > 3 of the medication categories (detailled in the protocol)
- Used a prohibited migraine prophylactic medication, device or procedure within 2 months prior to the start of the baseline phase (Refer to Section 6.5 for the list
of excluded medications, devices and procedures)
- Changing the dose of a concomitant medication that is not prescribed for migraine prophylaxis but that may have migraine prophylaxis effects within 1 month prior to screening. (Refer to Section 6.4 and Section 6.5 for the list of these medications)
- Received botulinum toxin in the head and/or neck region within 4 months prior to Screening
- History or evidence of 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.
- Excluded medical conditions include but not limited to:
∙ Currently diagnosed with fibromyalgia, and/or chronic pelvic pain
∙ History of major psychiatric disorder (such as schizophrenia or other
psychotic disorders, bipolar disorder, obsessive-compulsive disorder,
post-traumatic stress disorder), or current evidence of depression based on a Beck Depression Inventory (BDI)-II total score > 24 at screening.
∙ History of seizure disorder or other significant neurological conditions other than migraine
∙ Poorly controlled hypertension in the judgment of the investigator, or systolic blood pressure (BP) ≥ 160 mm Hg or diastolic BP ≥ 100 mm Hg as measured at the screening or week -4 study visits
∙ Myocardial infarction (MI), stroke, transient ischemic attack (TIA), unstable angina, coronary artery bypass surgery or other revascularization procedure within 12 months prior to screening
- 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 since ending treatment on another investigational device or drug study(-ies), or previous discontinuation from another drug study due to a serious adverse event |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in monthly migraine days from baseline to the last 4 weeks of the
12-week double-blind treatment phase |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change in monthly migraine days from baseline to the last 4 weeks of the
12-week double-blind treatment phase, calculated based on the following: (number of migraine days during the last 4 weeks of the double-blind treatment phase, ie, between weeks 9 and 12) - (number of migraine days during the 4-week baseline phase)
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E.5.2 | Secondary end point(s) |
Efficacy:
• At least a 50% reduction from baseline in monthly migraine days in the last 4 weeks of
the 12-week double-blind treatment phase
• Change from baseline on monthly migraine-specific medication
treatment days in the last 4 weeks of the 12-week double-blind
treatment phase
•Change from baseline in cumulative monthly headache hours in the last 4 weeks of the 12-week double-blind treatment phase
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 | No |
E.6.3 | Therapy | Yes |
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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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
| 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Canada |
Czech Republic |
Denmark |
Finland |
Germany |
Norway |
Poland |
Sweden |
United Kingdom |
United States |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 1 |