E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment-resistant Migraine |
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E.1.1.1 | Medical condition in easily understood language |
Migraine headaches that do not respond to currently available medications |
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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 | LLT |
E.1.2 | Classification code | 10027602 |
E.1.2 | Term | Migraine headache |
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 test the hypothesis that galcanezumab is superior to placebo in the prevention of migraine in patients with treatment-resistant migraine |
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E.2.2 | Secondary objectives of the trial |
To compare galcanezumab with placebo with respect to:
• prevention of migraine in the episodic migraine subpopulation
• 50% response rate
• change in functioning
• 75% response rate
• 100% response rate
• safety and tolerability
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients are 18 to 75 years of age (inclusive) at the time of screening.
Have a diagnosis of migraine as defined by IHS ICHD-3 guidelines (1.1, 1.2, or 1.3) (ICHD-3 2018), with a history of migraine headaches of at least 1 year prior to Visit 1, and migraine onset prior to age 50.
Prior to Visit 1, have a history of at least 4 migraine headache days and at least 1 headache-free day per month on average within the past 3 months.
Prior to Visit 1, have documentation (medical or pharmacy record or by physician’s confirmation) of previous failure to 2 to 4 migraine preventive medication categories in the past 10 years from the following list due to inadequate efficacy (that is, maximum tolerated dose for at least 2 months) and/or safety/tolerability reasons.
a) propranolol or metoprolol
b) topiramate
c) valproate or divalproex
d) amitriptyline
e) flunarizine
f) candesartan
g) botulinum toxin A or B (if documented that botulinum toxin was taken for chronic migraine)
h) medication locally approved for prevention of migraine |
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E.4 | Principal exclusion criteria |
• Are currently enrolled in or have participated within the last 30 days or within 5 half-lives (whichever is longer) in a clinical trial involving an investigational product.
• Current use or prior exposure to galcanezumab or another CGRP antibody.
• History of persistent daily headache, cluster headache or migraine subtypes including hemiplegic (sporadic or familial) migraine, ophthalmoplegic migraine, and migraine with brainstem aura (basilar-type migraine) defined by IHS ICHD-3.
• Are currently receiving medication or other treatments for the prevention of migraine headaches. Patients must have discontinued such treatment at least 5 days prior to starting the baseline period. Botulinum toxin A and B that has been administered in the head or neck area for migraine prevention must be discontinued at least 3 months prior to starting the baseline period. Nerve block or device use (such as transcranial magnetic stimulation) in the head or neck area or for migraine prevention must be discontinued at least 30 days prior to starting the baseline period.
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E.5 End points |
E.5.1 | Primary end point(s) |
The overall mean change from baseline in the number of monthly migraine headache days during the 3-month double-blind treatment phase in the total population (episodic and chronic migraine). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 month double blind treatment phase. |
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E.5.2 | Secondary end point(s) |
• The overall mean change from baseline in the number of monthly migraine headache days during the 3-month double-blind treatment phase in patients with episodic migraine
• The percentage of patients with ≥50% reduction from baseline in monthly migraine headache days during the 3 month double-blind treatment phase
• The mean change from baseline in the Role Function-Restrictive domain score of the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1) at Month 3
• The percentage of patients with ≥75% reduction from baseline in monthly migraine headache days during the 3 month double-blind treatment phase
• The percentage of patients with 100% reduction from baseline in monthly migraine headache days during the 3 month double-blind treatment phase
• Analysis of:
o treatment-emergent adverse events (TEAEs)
o serious adverse events (SAEs)
o discontinuation due to adverse events (AEs)
o discontinuation rates
o vital signs and weight
o electrocardiograms (ECGs)
o laboratory measures |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 month double blind treatment phase. |
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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 | Yes |
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 | Yes |
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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
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 |
Belgium |
Canada |
Czech Republic |
Denmark |
France |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Spain |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |