A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AMG 334 in Migraine Prevention
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 483
- 试验地点
- 1
- 主要终点
- CHU Substudy: Number of Participants Who Self-administered a Full Dose, Partial Dose, or No Dose of Erenumab
研究概览
简要总结
A study to evaluate the effect of erenumab compared to placebo on the change from baseline in monthly migraine days in participants with episodic migraine.
详细描述
The study is composed of an initial screening phase (up to 3 weeks), a 4-week baseline phase, a 12-week double-blind treatment phase (DBTP), an open-label treatment phase (OLTP) for up to 256 weeks, and an 8-week safety follow-up (12 weeks after the last dose of investigational product [IP]).
In the DBTP participants were to be randomized in a 3:2:2:2 ratio to placebo, erenumab 7 mg, erenumab 21 mg, or erenumab 70 mg.
During the open-label treatment phase, participants were to receive erenumab 70 mg QM from week 12 to week 264. After implementation of Protocol Amendment 3 (07 April 2016), participants remaining in the OLTP increased their dose to erenumab 140 mg QM up to week 264. The safety follow-up increased from an 8-week safety follow-up to a 12-week safety follow-up (16 weeks after the last dose of investigational product).
During the OLTP participants enrolled at sites in the United States could enroll in an optional clinical home use (CHU) substudy, per a country-specific protocol amendment dated 20 June 2016. Participants in the CHU substudy were to be randomized 1:1 into 1 of 2 treatment groups: erenumab 140 mg using a prefilled syringe or erenumab 140 mg using an autoinjector/pen. Day 1 of the CHU substudy corresponded with any OLTP study visit up through Week 256, as long as the participant had received at least 2 doses of erenumab 140 mg. During the CHU substudy, participants initially self-administered IP under site supervision on substudy day 1, and then self-administered IP at home on substudy days 29 and 57.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •History of migraine for more than12 months prior to screening
- •Migraine frequency: ≥ 4 and ≤ 14 migraine days per month in each of the 3 months prior to screening and during baseline phase
- •Headache frequency: < 15 headache days per month (with > 50% of the headache days being migraine days) in each of the 3 months prior to screening and during baseline phase
- •Demonstrated at least 80% compliance with the eDiary during baseline phase
排除标准
- •Older than 50 years of age at migraine onset
- •History of cluster headache or basilar or hemiplegic migraine headache
- •Unable to differentiate migraine from other headaches
- •No therapeutic response with > 2 of the following eight medication categories for prophylactic treatment of migraine after an adequate therapeutic trial. Medication categories are:
- •Category 1: Divalproex sodium, sodium valproate
- •Category 2: Topiramate
- •Category 3: Beta blockers (for example: atenolol, bisoprolol, metoprolol, nadolol, nebivolol, pindolol, propranolol, timolol)
- •Category 4: Tricyclic antidepressants (for example: amitriptyline, nortriptyline, protriptyline)
- •Category 5: Venlafaxine, desvenlafaxine, duloxetine, milnacipran
- •Category 6: Flunarizine, verapamil
- •Category 7: Lisinopril, candesartan
- •Category 8: Butterbur, feverfew, magnesium (≥ 600 mg/day), riboflavin (≥ 100 mg/day)
- •Overuse of acute migraine medications in any month during the 3 months prior to screening or during screening
研究组 & 干预措施
Placebo
Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase.
In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.
干预措施: Erenumab (Drug)
Placebo
Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase.
In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.
干预措施: Placebo (Drug)
Erenumab 7 mg QM
Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase.
In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.
干预措施: Erenumab (Drug)
Erenumab 21 mg QM
Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase.
In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.
干预措施: Erenumab (Drug)
Erenumab 70 mg QM
Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase.
In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.
干预措施: Erenumab (Drug)
CHU Substudy: Erenumab 140 mg PFS
Participants in the open-label treatment phase in the United States randomized to self-administer 140 mg erenumab via two 70 mg injections using a prefilled syringe (PFS) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).
干预措施: Erenumab PFS (Drug)
CHU Substudy: Erenumab 140 mg AI/Pen
Participants in the open-label treatment phase in the United States randomized to self-administer 140 mg erenumab via two 70 mg injections using an autoinjector/pen (AI)/pen) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).
干预措施: Erenumab AI/Pen (Drug)
结局指标
主要结局
CHU Substudy: Number of Participants Who Self-administered a Full Dose, Partial Dose, or No Dose of Erenumab
时间窗: CHU substudy day 29 (week 4) and day 57 (week 8)
To assess participants ability to administer a full dose of erenumab in home-use at day 29 (week 4) and day 57 (week 8), site staff called participants and asked whether the participant administered a full, partial, or no dose of erenumab. A full dose means that the entire volume of both prefilled syringes or autoinjector/pens were injected. Discontinued prior to dosing day indicates participants who had discontinued the investigational product and did not attempt to self-administer on day 29 or 57.
Change From Baseline in Monthly Migraine Days at Week 12
时间窗: 4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase
A migraine day was any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined as a migraine with or without aura. The change from baseline in monthly migraine days was calculated as the number of migraine days during the last 4 weeks of the 12-week double-blind treatment phase - the number of migraine days during the 4-week baseline phase.
次要结局
- CHU Substudy: Number of Participants With Treatment-emergent Adverse Events During the CHU Substudy(From first dose in the CHU substudy to end of substudy (up to 12 weeks))
- Number of Participants Who Developed Anti-erenumab Antibodies During the Double-blind Treatment Phase(12 weeks)
- Number of Participants With Treatment-emergent Adverse Events in the Open-label Treatment Phase(From first dose in the open-label treatment phase up to 12 weeks (participants receiving 70 mg only) or 16 weeks (participants with dose increased to 140 mg) after the last dose; a maximum of 268 weeks.)
- Number of Participants Who Developed Anti-erenumab Antibodies During the Open-label Treatment Phase(From week 12 up to 12 weeks (participants receiving 70 mg only) or 16 weeks (participants with dose increased to 140 mg) after the last dose; maximum 268 weeks.)
- Change From Baseline in Monthly Migraine Attacks at Week 12(4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase)
- Number of Participants With Treatment-emergent Adverse Events in the Double-blind Treatment Phase(From first dose of study drug in the double-blind treatment phase until the first dose of study drug in the open-label treatment phase (12 weeks) or up to 12 weeks after last dose for participants who did not enter the open-label treatment phase.)
- Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Week 12(4-week baseline phase and the last 4 weeks of the 12-week double-blind treatment phase)