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 |
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 main goal of this trial is to inform about long-term safety and tolerability of eptinezumab in participants with chronic cluster headache. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of eptinezumab in patients with cCH |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
* The participant has a diagnosis of cCH as defined by International Headache Society (IHS) International Classification of Headache Disorders third edition (ICHD-3) classification with a history of cCH of at least 12 months prior to the Screening Visit. * The participant has a medical history of onset of cluster headache at ≤ 50 years of age. * The participant has an adequately documented record of previous abortive, transitional and preventive medication use for cCH, for at least 12 months prior to the Screening Visit. * The participant is able to distinguish cluster headache attacks from other headaches (such as tension-type headaches, migraine). |
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E.4 | Principal exclusion criteria |
* The participant has experienced failure on a previous treatment targeting the calcitonin gene-related peptide (CGRP) pathway (anti-CGRP monoclonal antibodies [mAbs] and gepants). * The participant has confounding and clinically significant pain syndromes (for example, fibromyalgia, complex regional pain syndrome). * The participant has a history or diagnosis of chronic tension-type headache, 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 neurological accompaniments that are not typical of migraine aura (diplopia, altered consciousness, or longer than 1 hour). * Participants with a lifetime history of psychosis, bipolar mania, or dementia. Participants 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. * The participant has attempted suicide or is, at Screening Visit, at significant risk of suicide. * The participant has a history of clinically significant cardiovascular disease, including uncontrolled hypertension, vascular ischaemia or thromboembolic events (for example, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism). *The patient has confirmed or suspected active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at the time of Screening Visit or at Baseline Visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of Participants With Adverse Events |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From the day of first dose of study drug (Baseline [Week 0]) up to Week 56 |
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E.5.2 | Secondary end point(s) |
1. Conversion From Chronic Cluster Headache (cCH) to Episodic Cluster Headache: Number of Participants With No Cluster Headache Attacks for ≥3 Consecutive Months (≥13 Consecutive Weeks) 2. Change From Baseline in Weekly Number of Times an Abortive Therapy (Oxygen and/or Triptans) Was Used, Averaged Over the First 4 Weeks After Each Infusion 3. Change From Baseline in the Average Number of Weekly Attacks, Averaged Over the First 4 Weeks After Each Infusion 4. Change From Baseline in the 5-Point Self-Rating Pain Severity Scale, Averaged Over the First 4 Weeks After Each Infusion 5. Response: Number of Participants With ≥30% Reduction From Baseline in Number of Weekly Attacks Averaged Over the First 4 Weeks After Each Infusion 6. Response: Number of Participants With ≥50% Reduction From Baseline inNumber of Weekly Attacks Averaged Over the First 4 Weeks After Each Infusion 7. cCH Remission: Number of Participants With No Cluster Headache Attacks For ≥1 Month (5 Consecutive Weeks) 8. cCH Remission: Number of Participants With No Cluster Headache Attacks For ≥1 Month (5 Consecutive Weeks Between the First and Second Infusion) 9. cCH Remission: Number of Participants With No Cluster Headache Attacks For ≥1 Month (5 Consecutive Weeks Between the Second and Third Infusion) 10. cCH Remission: Number of Participants With No Cluster Headache Attacks For ≥1 Month (5 Consecutive Weeks Between the Third and Fourth Infusion) 11. cCH Remission: Number of Participants With No Cluster Headache Attacks For ≥1 Month (5 Consecutive Weeks Within the First 12 Weeks After the Fourth Infusion) 12. Number of Participants who Received a Transitional Therapy During the Treatment Period 13. Patient Global Impression of Change (PGIC) Score 14. Change From Baseline in Sleep Impact Scale (SIS) Domain Scores Over the Time 15. Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Score at Weeks 4, 16, 28, 40 and 48 16. Health Care Resources Utilization (HCRU) Score 17. Change From Baseline in the Work Productivity Activity Impairment: General Health Second Version (WPAI:GH2.0) Sub-Scores (Absenteeism, Presenteeism, Work Productivity Loss, Activity Impairment) at Weeks 4, 16, 28, 40 and 48 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Baseline (Week 0) to Week 48 2. Baseline (Week 0), Weeks 1 to 4, 13 to 16, 25 to 28, and 37 to 40 3. Baseline (Week 0), Weeks 1 to 4, 13 to 16, 25 to 28, and 37 to 40 4. Baseline (Week 0), Weeks 1 to 4, 13 to 16, 25 to 28, and 37 to 40 5. Weeks 1 to 4, 13 to 16, 25 to 28, and 37 to 40 6. Weeks 1 to 4, 13 to 16, 25 to 28, and 37 to 40 7. Baseline (Week 0) to Week 48 8. Baseline (Week 0) to Week 12 9. Week 12 to Week 24 10. Week 24 to Week 36 11. Week 36 to Week 48 12. Week 0 to Week 48 13. Baseline (Week 0) up to Week 48 14. Baseline (Week 0) up to Week 40 15. Baseline (Week 0) , Weeks 4, 16, 28, 40 and 48 16. Baseline (Week 0) , Weeks 4, 16, 28, 40 and 48 17. Baseline (Week 0) , Weeks 4, 16, 28, 40 and 48 |
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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 | No |
E.8.1.1 | Randomised | No |
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 | 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 | No |
E.8.2.3 | Other | No |
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 | 19 |
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 |
Finland |
France |
Netherlands |
Spain |
Germany |
Italy |
Denmark |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 30 |
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 | 0 |