A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study With an Open-Label Period to Evaluate the Efficacy and Safety of Fremanezumab for the Prophylactic Treatment of Migraine in Patients With Inadequate Response to Prior Preventive Treatments
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 838
- 试验地点
- 113
- 主要终点
- DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab
研究概览
简要总结
The purpose of this study is to evaluate the efficacy, safety, and tolerability of monthly and quarterly subcutaneous (sc) injections of fremanezumab compared with sc injections of placebo in participants with chronic migraine (CM) or episodic migraine (EM) who have responded inadequately to 2 to 4 classes of prior preventive treatments.
Approximately equal numbers of participants from each subgroup (CM and EM) are randomized in blinded-fashion 1:1:1 into one of 3 treatments for the subgroup - 2 active treatments and 1 placebo treatment- consisting of monthly injections for 3 months (up to Week 12). Then all participants continue into an open-label extension of 3 months (up to Week 24) during which everyone is administered sc injections of fremanezumab.
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 diagnosis of migraine with onset at ≤50 years of age.
- •Body weight ≥45 kilograms.
- •The participant has a history of migraine for ≥12 months prior to screening.
- •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 and the follow-up period and for 6.0 months after discontinuation of investigational medicinal product (IMP)
- •Men must be sterile, or if they are potentially fertile/reproductively competent (not surgically [that is; vasectomy] or congenitally sterile) and their female partners are of childbearing potential, must use, together with their female partners, acceptable birth control methods for the duration of the study and for 6.0 months after discontinuation of the investigational medicinal product (IMP).
- •Additional criteria apply, please contact the investigator for more information.
排除标准
- •At the time of screening visit, participant is receiving any preventive migraine medications, regardless of the medical indication for more than 5 days and expects to continue with these medications.
- •Participant has received onabotulinumtoxinA for migraine or for any medical or cosmetic reasons requiring injections in the head, face, or neck during the 3 months before screening visit.
- •The participant has used an intervention/device (for example; scheduled nerve blocks and transcranial magnetic stimulation) for migraine during the 2 months prior to screening.
- •The participant uses triptans/ergots as preventive therapies for migraine.
- •Participant uses non-steroidal anti-inflammatory drugs (NSAIDs) as preventive therapy for migraine on nearly daily basis for other indications. Note: Low dose aspirin (for example; 81 mg) used for cardiovascular disease prevention is allowed.
- •Additional criteria apply, please contact the investigator for more information.
研究组 & 干预措施
Placebo
Double-blind (DB) period: Participants with CM or EM will receive 3 injections of placebo 1.5 milliliters (mL) SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. Open-label (OL) period: Participants with CM or EM will receive fremanezumab (TEV-48125) 225 milligrams (mg) SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140.
干预措施: Fremanezumab (Drug)
Placebo
Double-blind (DB) period: Participants with CM or EM will receive 3 injections of placebo 1.5 milliliters (mL) SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. Open-label (OL) period: Participants with CM or EM will receive fremanezumab (TEV-48125) 225 milligrams (mg) SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140.
干预措施: Placebo (Drug)
Fremanezumab Quarterly
DB period: Participants with CM or EM will receive fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). OL period: Participants with CM or EM will receive fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140.
干预措施: Fremanezumab (Drug)
Fremanezumab Quarterly
DB period: Participants with CM or EM will receive fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). OL period: Participants with CM or EM will receive fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140.
干预措施: Placebo (Drug)
Fremanezumab Monthly
DB period: Participants with CM will receive fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM will receive fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). OL period: Participants with CM or EM will receive fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140.
干预措施: Fremanezumab (Drug)
Fremanezumab Monthly
DB period: Participants with CM will receive fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM will receive fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). OL period: Participants with CM or EM will receive fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140.
干预措施: Placebo (Drug)
结局指标
主要结局
DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab
时间窗: Baseline (Day -28 to Day -1), up to Week 12
A migraine day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period)\*28. Change was calculated as post-baseline value - baseline value.
次要结局
- DB Period: Percentage of Participants Reaching at Least 50 Percent (%) Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab(Baseline (Day -28 to Day-1), up to Week 12)
- DB Period: Number of Participants With Adverse Events (AEs) and Who Did Not Complete the Study Due to AEs(Baseline (Day 0) up to Week 12)
- OL Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results(Week 12 up to Week 24)
- DB Period: Percentage of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab(Baseline (Day -28 to Day-1), up to Week 4)
- OL Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results(Week 12 up to Week 24)
- DB Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results(Baseline up to Week 12)
- OL Period: Number of Participants With Shift From Baseline to Week 24 in ECG Parameters(Baseline, Week 24)
- DB Period: Change From Baseline in Monthly Average Number of Days of Use of Any Acute Headache Medications During the 12-Week Period After the First Dose of Fremanezumab(Baseline (Day -28 to Day -1), up to Week 12)
- DB Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results(Baseline up to Week 12)
- DB Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results(Baseline up to Week 12)
- DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period After the First Dose of Fremanezumab(Baseline (Day -28 to Day -1), up to Week 4)
- OL Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values(Week 12 up to Week 24)
- DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Period After the First Dose of Fremanezumab(Baseline (Day -28 to Day -1), up to Week 12)
- DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab(Baseline (Day -28 to Day -1), up to Week 4)
- OL Period: Number of Participants With AEs and Who Did Not Complete the Study Due to AEs(Week 12 up to Week 24)
- DB Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results(Baseline up to Week 12)
- DB Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values(Baseline up to Week 12)
- DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters(Baseline, Week 12)
- OL Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results(Week 12 up to Week 24)
- OL Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results(Week 12 up to Week 24)
- DB Period: Number of Participants Who Received Concomitant Medications for Adverse Events(Baseline up to Week 12)
- OL Period: Number of Participants Who Received Concomitant Medications for Adverse Events(Week 12 up to Week 24)