Clinical trial investigating the efficacy and safety of investigational drug TEV-48125 developed to prevent chronic cluster headache

Phase 1

• Conditions: Chronic Cluster headache (CCH); Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2016-003171-21-DE
• Lead Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-12-19
• Last Update Posted: 23 July 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

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 history of CCH 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 for more than 1 year without remission, or with remission periods lasting less than 1 month.
d. The patient has a total body weight of =45 kg.
e. 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.
f. 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 (12 weeks) where the primary endpoint is evaluated.
g. The patient 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.
h. The patient has at least 10 CH attacks during the run-in period.
i. 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.
j. Women may be included only if they have a negative serum beta-human chorionic gonadotropin (ß-HCG) test at screening, are sterile or postmenopausal, and are not lactating. Definitions of sterile and postmenopausal are given in Appendix E.
k. 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.
l. 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 discontinuation of the IMP. Definitions of women of non-childbearing potential, sterile women, and postmenopausal women; male contraception; and highly effective and acceptable birth control methods including examples are given in Appendix E.
m. The patient must be willing and able to comply with study restrictions, to remain at the clinic for the required duration during the study period and to return to the clinic for the follow-up

Exclusion Criteria

a. The patient has used systemic steroids for any medical reason (including treatment of the current CH cycle) within =7 days prior to screening.
b. The patient reports using butalbital on more than 10 days during the 4 weeks prior to screening or using butalbital on more than 10 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 15 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 the 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 (ALT and 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 evidence of clinically significant renal disease in the judgement of the investigator.
s. The patient cannot participate or successfully complete the study, in the opinion of their healthcare provider o

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified