Cluster Headache
Conditions
Interventions
Patients will complete a screening visit (visit 1) after providing written
informed consent, and eligible patients will enter a run-in period lasting at
least 1 week (+3 days) during which they will
Episodic Cluster Headache
Placebo
Prevention
Sponsors
TEVA Pharma
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: a. Patients are capable of giving signed informed consent as described in Appendix D which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. b. The patient is a man or woman 18 to 70 years of age, inclusive. c. The patient has a history of ECH according to ICHD-3 beta criteria (Headache Classification Committee of the IHS 2013) for *12 months prior to screening including the following: * Attacks of severe, strictly unilateral pain which is orbital, supraorbital, temporal or in any combination of these sites, lasting 15 to 180 minutes and occurring from once daily every other day to 8 times a day for more than half of the time when the disorder is active * The pain is associated with at least 1 of the following symptoms or signs: ipsilateral conjunctival injection, lacrimation, nasal congestion, rhinorrhea, forehead and facial sweating, miosis and/or ptosis and/or eyelid edema, and/or sense of restlessness or agitation. CH attacks occurring in periods lasting from 7 days to 1 year, separated by pain-free periods lasting at least 1 month. d. CH attacks of a new cluster cycle have started within 2 weeks (14 days, inclusive) prior to screening and, based on the patient*s previous medical history, it is expected that the patient*s CH attacks will continue for *6 weeks after the screening visit. e. The patient has a total body weight of *45 kg f. The patient is not using or using * 2 concomitant medications that are commonly prescribed as preventive treatments for CH (Appendix H), regardless of the indication for which the medication was prescribed. Patients must be on a stable dose and regimen for at least 2 weeks prior to screening and throughout the study. g. If a patient is receiving Botox, it should be in a stable dose regimen, considered as having *2 cycles of Botox prior to screening. The patient should not receive Botox during the run-in period up to the evaluation period (4 weeks) where the primary endpoint is evaluated. h. The patient has demonstrated compliance with the electronic headache diary during the run-in period by entry of headache data on 85% of days during the run-in period. i. The patient has at least 7 CH attacks during the run-in period. j. The patient is in good health in the opinion of the investigator as determined by a medical and psychiatric history; medical examination; 12-lead ECG; and serum chemistry, hematology, coagulation, and urinalysis. k. Women may be included only if they have a negative serum beta-human chorionic gonadotropin (*-HCG) test at screening, are sterile or postmenopausal, and are not lactating. Definitions of sterile and postmenopausal are given in Appendix E. l. Women of childbearing potential (WOCBP) whose male partners are potentially fertile (ie, no vasectomy) must use highly effective birth control methods for the duration of the study (ie, starting at screening) and for 7.5 months after discontinuation of IMP. m. Men must be sterile, or if they are potentially fertile/reproductively competent (not surgically [eg, vasectomy] or congenitally sterile) and their female partners are of childbearing potential, must agree to use, together with their female partners, acceptable birth control methods for the duration of the study and for 7.5 months after
Exclusion criteria
Exclusion criteria: a. The patient has used systemic steroids for any reason (including treatment of the current CH cycle) within *7 days prior to screening. b. The patient reports using butalbital on more than 7 days during the 4 weeks prior to screening or using butalbital on more than 3 days during the screening/run-in period. c. The patient reports using opioids on more than 15 days during the 4 weeks prior to screening or using opioids on more than 4 days during the screening/run-in period. d. The patient has used an intervention/device (eg, scheduled nerve blocks) for headache during the 4 weeks prior to screening. e. The patient has clinically significant hematological, renal, endocrine, immunologic, pulmonary, gastrointestinal, genitourinary, cardiovascular, neurologic, hepatic, or ocular disease at the discretion of the investigator. f. The patient has evidence or medical history of clinically significant psychiatric issues determined at the discretion of the investigator. g. The patient has a history of any suicide attempt in the past or current active suicidal ideation, as measured by the eC-SSRS. h. The patient has a history of clinically significant cardiovascular disease or vascular ischemia (such as myocardial, neurological [eg, cerebral ischemia], peripheral extremity ischemia, or other ischemic event) or thromboembolic events (arterial or venous thrombotic or embolic events), such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism. i. The patient has a past or current history of cancer or malignant tumor in the past 5 years, except for appropriately treated non-melanoma skin carcinoma. j. The patient is pregnant or lactating. k. The patient has a history of hypersensitivity reactions to injected proteins, including monoclonal antibodies. l. The patient has participated in a clinical study of a new chemical entity or a prescription medicine within 2 months or 5 half-lives before administration of the first dose of the IMP, whichever is longer. m. The patient has participated in a clinical study of a monoclonal antibody within 3 months or 5 half-lives before administration of the first dose of the IMP, whichever is longer, unless it is known that the patient received placebo during the study. n. The patient has a history of prior exposure to a monoclonal antibody targeting the CGRP pathway (AMG 334, ALD304, LY2951742, or fremanezumab). If patient has participated in a clinical study with any of these monoclonal antibodies, it has to be confirmed that the patient received placebo in order to be eligible for this study). o. The patient has any finding in the baseline 12-lead ECG considered clinically significant in the judgment of the investigator. p. The patient has any finding that, in the judgment of the investigator, is a clinically significant abnormality, including serum chemistry, hematology, coagulation, and urinalysis test values (abnormal tests may be repeated for confirmation). q. The patient has hepatic enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) >1.5 × the upper limit of normal (ULN) range after confirmation in a repeat test, or the patient has suspected hepatocellular damage that fulfills criteria for Hy*s law at screening. r. The patient has serum creatinine >1.5 × the ULN or evi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| * the mean change from baseline (run-in period) in the weekly average number of cluster headache (CH) attacks during the 4-week period after administration of the first dose of the investigational medicinal product (IMP), ie, based on week 0 to 4 data * the proportion of patients with a *50% reduction from baseline (run-in period) in the weekly average number of CH attacks during the 4 week period after the first dose of the IMP, ie, based on week 0 to 4 data * the mean change from baseline (run-in period) in the number of CH attacks during the 12 week period after administration of the first dose of the IMP, ie, based on week 0 to 12 data * the mean change from baseline (run-in period) in the number of CH attacks during the 4 week period after administration of the third dose of the IMP, ie, based on week 8 to 12 data * the mean change from baseline (run-in period) in the weekly average number of days with use of cluster-specific acute headache medications (triptans and ergot compounds) during the 12 week period after administration of the first dose of the IMP, ie, based on week 0 to 12 data * the mean change from baseline (run-in period) in the weekly average number of days oxygen is used to treat ECH during the 12-week period after administration of the first dose of the IMP, ie, based on week 0 to 12 data * assessment of patient*s perceived improvement, as measured by the Patient-Perceived Satisfactory Improvement (PPSI) at 1, 4, 8, and 12 weeks after administration of the first dose of the IMP relative to baseline (day 0) | — |
Secondary
| Measure | Time frame |
|---|---|
| * occurrence of adverse events throughout the study * clinical laboratory (serum chemistry, hematology, coagulation, and urinalysis) test results at each visit * vital signs (systolic and diastolic blood pressure, oral temperature, and pulse rate) measurements at each visit. Note: Oxygen saturation will be measured in cases of suspected anaphylaxis and severe hypersensitivity. Respiratory rate will also be measured in these cases but not as a standard vital sign. * 12 lead electrocardiogram (ECG) findings at screening, baseline, and week 12 * use of concomitant medication during the study * clinically significant changes in physical examinations, including body weight * injection site reaction (ie, erythema, induration, and ecchymosis) and injection site pain assessments * occurrence of hypersensitivity/anaphylaxis reactions * suicidal ideation and behavior as measured by the electronic Columbia Suicide Severity Rating Scale (eC-SSRS) | — |
Countries
The Netherlands
Outcome results
None listed