E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Episodic or chronic migraine headache |
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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.1.3 | 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 long-term safety and tolerability of LY2951742 in patients suffering from migraine, with or without aura, for up to 1 year of treatment. |
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E.2.2 | Secondary objectives of the trial |
To characterize the long-term pharmacokinetics and pharmacodynamics of LY2951742.
To characterize the long-term immunogenicity of LY2951742.
To evaluate the long-term effectiveness of LY2951742 in the prevention of migraine.
To evaluate the long-term effect of LY2951742 on health outcomes and quality of life.
To evaluate patient satisfaction with medication
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients are 18 to 65 years of age (inclusive) at the time of screening.
migraine onset prior to age 50
- Have a diagnosis of migraine as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta guidelines (1.1,1.2, or 1.3) (ICHD-3 beta, Cephalalgia 2013), with a history of migraine headaches of at least 1 year prior to Visit 1.
- Prior to Visit 1, a history of 4 or more migraine headache days per month on average for the past 3 months. |
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E.4 | Principal exclusion criteria |
Are currently enrolled in any other clinical trial involving any investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.
Have participated within the last 30 days or within 5 half-lives (whichever is longer) in a clinical trial involving an investigational product. If the investigational product’s half-life is not known, 6 months should have passed prior to Visit 1.
Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic proteins, or to LY2951742.
Currently receiving medication or other treatments for the prevention of migraine headaches. Patients must have discontinued such treatment at least 30 days prior to Visit 2
History of persistent daily headache, cluster headache or migraine
subtypes including hemiplegic (sporadic or familial) migraine,
ophthalmoplegic migraine, and migraine with brainstem aura (basilartype
migraine) defined by IHS ICHD-3 beta. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Analysis of:
- treatment-emergent adverse events (TEAEs)
- discontinuation rates
- vital signs and weight
- electrocardiograms (ECGs)
- laboratory measures
- other safety parameters, including suicidality using the Columbia Suicide Severity Rating Scale (C-SSRS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline to 12 months in an open-label treatment phase, |
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E.5.2 | Secondary end point(s) |
-Assessment of serum concentrations of LY2951742 to enable a pharmacokinetic evaluation.
-Assessment of plasma concentrations of CGRP to enable a pharmacodynamic evaluation of target engagement of LY2951742.
-Assessment of the development and consequences of anti-drug antibodies (ADA) to LY2951742.
-Collection of samples for subsequent evaluation of neutralizing ADAs upon availability of the validated assay.
-Mean change from baseline in the number of migraine headache days;
-Mean change from baseline in the number of headache days;
-Proportion of patients meeting 50% response criteria (reduction of at least 50% in the number of migraine headache days);
-Mean changes in patient’s global impression of illness as measured by PGI-Severity at baseline and PGI-Improvement post-baseline
-Mean change from baseline to endpoint in the evaluation of the Migraine Disability Assessment test (MIDAS) total score and individual items;
-Mean change from baseline to endpoint in the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1) total score and individual domains;
-Analysis of safety parameters
-Satisfaction with medication will be assessed using the Patient Satisfaction with Medication Questionnaire-Modified (PSMQ-M).
-Satisfaction with and ease of use of the device for injection will be assessed using the Subcutaneous Administration Assessment Questionnaire (SQAAQ) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Assessment of the development and consequences of anti-drug antibodies to LY2951742.
Collection of samples for subsequent evaluation of neutralizing anti-drug antibodies. |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
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 | 13 |
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 |
France |
Hungary |
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 | |
E.8.9.1 | In the Member State concerned months | 23 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 23 |