E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Episodic cluster headache |
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E.1.1.1 | Medical condition in easily understood language |
Recurrent severe headaches on one side of the head |
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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 | 24.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059133 |
E.1.2 | Term | Cluster headache |
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 |
The purpose of this study is to evaluate the efficacy of eptinezumab in patients with episodic Cluster Headache (eCH) |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of eptinezumab on health-related quality of life, health care resource utilization, and work productivity |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• The patient has episodic cluster headache, as defined by IHS ICHD-3 classification, with an adequately documented record or reliable documented history of eCH of at least 12 months prior to Screening Visit 1. • The patient has a prior history of cluster period(s) lasting 6 weeks or longer, when untreated. • The patient is able to distinguish cluster headache attacks from other headaches (i.e. tension-type headaches, migraine). • The patient is, at Screening Visit 2, in cluster headache bout, characterized by the presence of at least one typical cluster headache attack, that started not later than 1 week prior to Screening Visit 2. • The patient has a medical history of cluster headache from <60 years of age. |
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E.4 | Principal exclusion criteria |
• The patient has experienced failure on a previous treatment targeting the calcitonin gene-related peptide (CGRP) pathway (anti-CGRP mAbs and gepants). • The patient has confounding and clinically significant pain syndromes (for example, fibromyalgia, complex regional pain syndrome). • The patient has a history or diagnosis of hypnic headache, hemicrania continua, new daily persistent headache, chronic migraine or unusual migraine subtypes such as hemiplegic migraine (sporadic and familial), recurrent painful ophthalmoplegic neuropathy, migraine with brainstem aura and migraine with neurological accompaniments that are not typical of migraine aura (diplopia, altered consciousness, or long duration). • Patients with a lifetime history of psychosis, bipolar mania, or dementia are excluded. Patients with other psychiatric conditions whose symptoms are not controlled or who have not been adequately treated for a minimum of 6 months prior to Screening Visit 2 are also excluded. • The patient is, at Screening Visit 2, at significant risk of suicide. • The patient has a history of clinically significant cardiovascular disease, including uncontrolled hypertension, ischaemia or thromboembolic events (for example, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism). |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change from baseline in number of weekly attacks |
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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) |
2. Response: >= 50% reduction in number of weekly attacks 3. Change from baseline in weekly number of times an abortive therapy was used 4. Change from baseline in the number of daily attacks 5. Change from baseline in weekly number of days with less than 3 attacks per day 6. Time to resolution of cluster headache bout within 4 weeks after the first Investigational Medicinal Product (IMP) infusion 7. Number of attacks starting within 24 hours of the start of the first infusion 8. Change from baseline in the daily mean score on 5-point self-rating pain severity scale 9. Change from baseline to Week 1 in number of attacks 10. Change from baseline to Week 2 in number of attacks 11. Response: >= 50% reduction in number of attacks in Week 1 12. Response: >= 30% reduction in number of attacks in Week 1 13. Response: >= 30% reduction in number of weekly attacks (Weeks 1-2) 14. Change from baseline in weekly integrated measure of frequency and intensity of pain (Weeks 1-2): For each week add the intensity (worst pain on 5-point self-rating pain severity scale) for each attack experienced during that week 15. Change from baseline to Week 1 in integrated measure of frequency and intensity of pain: For Week 1 add the intensity (worst pain on 5-point self-rating pain severity scale) for each attack experienced during that week 16. Change from baseline to Week 2 in weekly integrated measure of frequency and intensity of pain: For Week 2 add the intensity (worst pain on 5-point self-rating pain severity scale) for each attack experienced during that week 17. Change from baseline in the number of weekly attacks 18. Change from baseline in weekly integrated measure of frequency and intensity of pain (Weeks 1-4). For each week add the intensity (worst pain on 5-point self-rating pain severity scale) for each attack experienced during that week for each attack experienced during that week. 19. Change from baseline in the mean score on 5-point selfrating pain severity scale (average per week) for Weeks 1,2,3 and 4 20. Change from baseline in number of attacks for Week 1,2,3 and 4 21. Patient Global Impression of Change (PGIC) score at Week 1,2 and 4 22. Change from baseline in Sleep Impact Scale (SIS) domain score at Weeks 2 and 4 23. Change from baseline in EQ-5D-5L Visual Analogue Scale (VAS) at Week 2 and 4 24. Health Care Resources Utilization (HCRU) at Week 4 25. Change from baseline in Health Care Resources Utilization (HCRU) at Week 4 25. Change from baseline in the Work Productivity Activity Questionnaire at Week 4. General Health second version (WPAI:GH2.0) subscores (Absenteeism, Presenteeism, Work productivity loss, Activity impairment) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
2. Weeks 1-2 3. Weeks 1-2 4. Days 1-3 5. Weeks 1-2 6. From baseline to Week 4 7. From first infusion to 24-hours post dose 8. Days 1-3 9. From baseline to Week 1 10. From baseline to Week 2 11. Week 1 12. Week 1 13. Weeks 1-2 14. Weeks 1-2 15. Week 1 16. Week 2 17. Weeks 1-4 18. Weeks 1-4 19. Weeks 1, 2, 3 and 4 20. Weeks 1, 2, 3 and 4 21. Weeks 1, 2 and 4 22. Weeks 2 and 4 23. Weeks 2 and 4 24. Week 4 25. Week 4 |
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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 | 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 | 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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 86 |
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 |
United States |
Georgia |
Russian Federation |
Belgium |
Czechia |
Denmark |
Estonia |
Finland |
France |
Germany |
Greece |
Italy |
Netherlands |
Norway |
Portugal |
Spain |
Sweden |
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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |