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 Epidosic Cluster Headache
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 169
- 试验地点
- 82
- 主要终点
- Mean Change From Baseline in the Weekly Average Number of Cluster Headache (CH) Attacks During the 4-Week Period After Administration of the First Dose of the IMP
研究概览
简要总结
This is a 13-week, multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study to compare the efficacy and safety of 2 dose regimens of TEV-48125 (Fremanezumab) versus placebo in adult participants for the prevention of ECH.
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 ECH according to the International Classification of Headache Disorders - 3 beta criteria (Headache Classification Committee of the International Headache Society [IHS] 2013) for ≥12 months prior to screening.
- •The participant has a total body weight of ≥45 kg (99 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 for the duration of the study.
- •If a participant is receiving Botox, it should be in a stable dose regimen, 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 (4 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 CH cycle within ≤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 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 will receive placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.
干预措施: Placebo (Drug)
Fremanezumab 675 mg/Placebo/Placebo
Participants will receive placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 milligrams (mg) administered as 3 subcutaneous injections (225 mg/1.5 milliliters [mL]) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
干预措施: Fremanezumab (Drug)
Fremanezumab 900/225/225 mg
Participants will receive fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
干预措施: Fremanezumab (Drug)
结局指标
主要结局
Mean Change From Baseline in the Weekly Average Number of Cluster Headache (CH) Attacks During the 4-Week Period After Administration of the First Dose of the IMP
时间窗: Baseline (Week 0), up to Week 4
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 weekly average number of CH attacks during the 4-week period after administration of the first dose of study drug (based on Week 0 to 4 data) is reported.
次要结局
- 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, Weeks 1, 4, 8, and 12)
- Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results(Baseline up to Week 12)
- Mean Change From Baseline in Weekly Average Number of CH Attacks During the 4-Week Period After Administration of the Third Dose of the IMP(Baseline (Week 0), Week 8 up to Week 12)
- Mean Change From Baseline 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 the First Dose of the IMP(Baseline (Week 0), up to Week 12)
- Mean Change From Baseline in the Weekly Average Number of Days Oxygen Was Used to Treat Episodic Cluster Headache (ECH) During the 12-Week Period After the First Dose of the IMP(Baseline (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 Who Received Concomitant Medications(Baseline up to Week 12)
- Percentage of Participants With a ≥50% Reduction From Baseline in the Weekly Average Number of CH Attacks During the 4-Week Period After the First Dose of the IMP(Baseline (Week 0), up to Week 4)
- Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results(Baseline up to Week 12)
- Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters(Baseline up to Week 12)
- Number of Participants With Injection Site Reactions(Baseline up to Week 12)
- Number of Participants With Hypersensitivity/Anaphylaxis Reactions(Baseline up to Week 12)
- Mean Change From Baseline in Weekly Average Number of CH Attacks During the 12-Week Period After Administration of the First Dose of the IMP(Baseline (Week 0), up to Week 12)
- Number of Participants With Adverse Events (AEs)(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)