A Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel-Group Study Comparing the Efficacy and Safety of 2 Dose Regimens (Intravenous/Subcutaneous and Subcutaneous) of TEV-48125 Versus Placebo for the Prevention of Chronic Cluster Headache
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 259
- 试验地点
- 83
- 主要终点
- Mean Change From Baseline in the Overall Monthly Average Number of CH Attacks Up to Week 12
研究概览
简要总结
The purpose of the current study is to evaluate the efficacy and safety of Fremanezumab (TEV-48125), in the prevention of CCH in adult participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant has a history of CCH according to the International Classification of Headache Disorders - 3 beta criteria (Headache Classification Committee of the International Headache Society [IHS] 2013) for greater than or equal to (≥)12 months prior to screening.
- •The participant has a total body weight of ≥45 kilograms (kg) (99 pounds [lbs]).
- •The participant is in good health in the opinion of the Investigator.
- •Women of childbearing potential (WOCBP) whose male partners are potentially fertile (that is, no vasectomy) must use highly effective birth control methods for the duration of the study.
- •Men must be sterile, or if they are potentially fertile/reproductively competent (not surgically [for example, vasectomy] or congenitally sterile) and their female partners are of childbearing potential, must agree to use, together with their female partners, acceptable birth control.
- •If a participant is receiving Botox, it should be in a stable dose regimen, which is considered as having ≥2 cycles of Botox prior to screening. The participant should not receive Botox during the run-in period up to the evaluation period (12 weeks) where the primary endpoint is evaluated.
- •Additional criteria apply, please contact the Investigator for more information.
排除标准
- •The participant has used systemic steroids for any medical reason (including treatment of the current cluster headache (CH) cycle within less than or equal to (≤)7 days prior to screening. The participant has used an intervention/device (for example, scheduled nerve blocks) for headache during the 4 weeks prior to screening.
- •The participant has clinically significant hematological, renal, endocrine, immunologic, pulmonary, gastrointestinal, genitourinary, cardiovascular, neurologic, hepatic, or ocular disease at the discretion of the Investigator.
- •The participant has evidence or medical history of clinically significant psychiatric issues determined at the discretion of the Investigator.
- •The participant has a past or current history of cancer or malignant tumor in the past 5 years, except for appropriately treated non-melanoma skin carcinoma.
- •The participant is pregnant or lactating.
- •The participant has a history of hypersensitivity reactions to injected proteins, including monoclonal antibodies.
- •The participant 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 investigational medicinal product (IMP), whichever is longer, unless it is known that the participant received placebo during the study.
- •The participant has a history of prior exposure to a monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) pathway (AMG 334, ALD304, LY2951742, or fremanezumab). If participant has participated in a clinical study with any of these monoclonal antibodies, it has to be confirmed that the participant received placebo in order to be eligible for this study.
- •The participant is an employee of the sponsor/participating study center who is directly involved in the study or is the relative of such an employee.
- •The participant has an active implant for neurostimulation used in the treatment of CH.
- •The participant is a member of a vulnerable population (for example, people kept in detention).
- •The participant has a history of alcohol abuse prior to screening and/or drug abuse that in the Investigator's opinion could interfere with the study evaluations or the participant's safety.
- •Additional criteria apply, please contact the Investigator for more information.
研究组 & 干预措施
Placebo
Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.
干预措施: Placebo (Drug)
Fremanezumab 675/225/225 mg
Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 milligrams (mg) as 3 subcutaneous injections (225 mg/1.5 milliliters [mL]) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
干预措施: Fremanezumab (Drug)
Fremanezumab 675/225/225 mg
Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 milligrams (mg) as 3 subcutaneous injections (225 mg/1.5 milliliters [mL]) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
干预措施: Placebo (Drug)
Fremanezumab 900/225/225 mg
Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
干预措施: Fremanezumab (Drug)
Fremanezumab 900/225/225 mg
Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Change From Baseline in the Overall Monthly Average Number of CH Attacks Up to Week 12
时间窗: Baseline Period (from at least Week -4 to Week 0), Up to Week 12
A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. Least Squares (LS) mean calculated using analysis of covariance (ANCOVA) model with baseline preventive medication use (yes or no), sex, region (United States \[US\]/Canada or other), and treatment as fixed effects and the baseline number of CH attacks as a covariate. Change from baseline in the overall monthly average number of CH attacks during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported.
次要结局
- Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results(Baseline up to Week 12)
- Mean Change From Baseline in the Monthly Average Number of CH Attacks at Week 4 and Week 12(Baseline Period (from at least Week -4 to Week 0), Week 4 and Week 12)
- Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results(Baseline up to Week 12)
- Percentage of Participants With a ≥50% Reduction From Baseline in the Monthly Average Number of CH Attacks Up to Week 12(Baseline Period (from at least Week -4 to Week 0) up to Week 12)
- Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values(Baseline up to Week 12)
- Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters(Baseline to Week 12)
- Mean Change From Baseline in the Overall Weekly Average Number of Days With Use of Cluster-Specific Acute Headache Medications (Triptans and Ergot Compounds) Up to Week 12(Baseline Period (from at least Week -4 to Week 0), Up to Week 12)
- Mean Change From Baseline in the Weekly Average Number of Days Oxygen Was Used to Treat CCH Up to Week 12(Baseline Period (from at least Week -4 to Week 0), Up to Week 12)
- Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12(Baseline and Weeks 1, 4, 8, and 12)
- Number of Participants With Adverse Events (AEs)(Baseline up to Week 12)
- Number of Participants With Injection Site Reactions(Baseline up to Week 12)
- Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)(Baseline up to Week 12)