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 |
Recurrent, severe, painful (one-sided) headache attacks |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009698 |
E.1.2 | Term | Cluster headaches |
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 |
The primary objective of this study is to test the hypothesis that erenumab is superior to placebo in the reduction of weekly CH attacks in weeks 5 and 6 (days 29-42) in the erenumab group compared to placebo versus baseline |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect of erenumab compared to placebo on the proportion of patients with at least a 50% reduction from baseline in weekly CH attacks at week 5 and 6 (days 29-42).
2. To evaluate the effect of erenumab compared to placebo on the change from baseline in the GPI-Scale at week 6
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
During Screening: 1) Patient is capable of understanding the nature, significance and implications of the clinical trial . Written informed consent must be obtained before any assessment is performed
2) Adult’s ≥18 and < 65 years (max. 64 years old) upon entry into screening.
3) Documented history of chronic cluster headache for ≥12 months prior to screening according to the International Classification of Headache Disorders-3rd Edition (ICHD-3)
4) Insufficient efficacy OR tolerability OR contraindications of approved cluster headache prophylactic medications. Insufficient efficacy and tolerability as determined by the patient.
5) Sufficient acute attack treatment with triptans or oxygen based on the patient´s history
6) The patient is able to distinguish cluster headache attacks from other headaches (i.e. tension-type headaches).
During Baseline: This inclusion criteria should not be shared with potential patients:
7) At least 9 cluster headache attacks as defined by the ICHD-3 in 7 days during the baseline epoch (SPII), confirmed by patient-reported eDiary entries.
8) Attacks must have occurred on more than 50% of days of the baseline epoch (SPII).
9) ≥ 90% patient-reported eDiary compliance during the Baseline epoch, compliance is measured as interacting with e-Diary at least once a day
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E.4 | Principal exclusion criteria |
Exception from the Exclusion Criteria:
Diagnosis of other primary headache diseases including the diagnosis of episodic cluster headache according to the International Classification of Headache Disorders, 3rd Edition (ICHD-3), excluding episodic tension type headache and migraine. Headache freedom from the historic diagnosis of migraine has to be at least one year prior to screening. . If patients have on average <=1 migraine attack per month within a year and can distinguish between migraine attacks and cluster attacks, they are allowed to participate
Use of a prophylactic cluster headache prophylaxis medication within 5 half-lives prior to the start of the baseline phase. (specified in Table 5.1)
Parallel use of an SPG stimulator or parallel use of a device for the acute/preventive treatment of cCH;
Significant comorbidities or psychiatric disorders, drug abuse or opioid use
Diagnosis or history of severe psychiatric or personality disorder
Concurrent use of other therapeutic monoclonal antibodies
Diagnosis of chronic or active hepatitis
Evidence of drug, opioid or alcohol abuse or dependence within 12 months prior to screening, based on medical records or patient self-report
History of use of psilocybin (mushrooms), LSD, MDMA or 2-bromo-LSD within 2 months prior to baseline
Diagnosis or history of significant active or unstable psychiatric disease, such as bipolar disorder, schizophrenia, personality disorders, or other serious mood or anxiety disorders. Patients with anxiety disorder and/or major depressive disorder are permitted in the study if they are considered by the investigator to be stable and are taking no more than one medication per disorder. Patients must have been on a stable dose within the 3 months prior to the start of the baseline phase.
Hepatic disease by history or total bilirubin ≥2×ULN or ALT or AST ≥3xULN as assessed by central laboratory at initial screening
History of severe constipation, defined as less than 3 bowel movements /week not adequately manageable by routine medical treatment, within 3 months prior to screening.
Prior known treatment of any duration with a CGRP receptor mAb (erenumab).
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E.5 End points |
E.5.1 | Primary end point(s) |
Reduction from baseline (averaged per 7 days) in weekly CH attacks averaged for 7 days over the last 2 weeks (days 29-42) of the double-blind epoch |
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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) |
1.) Number of patients achieving at least a 50% reduction from baseline in weekly CH attacks averaged over the last 2 weeks (days 29-42) of the double-blind epoch.
2.) Patient Global Impression of Improvement (PGI-I) at week 6 (day 42). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of Life (QOL), Tolerability |
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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) | 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 | 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 | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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End of trial will occur when last patient completes last visit (LPLV) |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |