A Phase 2, Randomized, Double-blind Placebo-controlled Study to Test the Efficacy and Safety of KPL-301 in Giant Cell Arteritis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 49
- 主要终点
- Time to Flare by Week 26
研究概览
简要总结
The primary objective of the study is to evaluate the efficacy of mavrilimumab (KPL-301) versus placebo, co-administered with a 26-week corticosteroid taper, for maintaining sustained remission for 26 weeks in subjects with new onset or relapsing/refractory giant cell arteritis (GCA).
详细描述
This Phase 2 randomized, double-blind, placebo-controlled proof of concept study will evaluate the efficacy and safety of mavrilimumab co-administered with a 26-week corticosteroid taper in subjects with GCA. The study will consist of a screening period (up to 6 weeks), a 26-week double-blind placebo-controlled period during which subjects will receive blinded mavrilimumab or placebo co-administered with a 26-week corticosteroid taper, and a 12-week washout safety follow-up period during which subjects will discontinue and wash off blinded mavrilimumab or placebo.
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
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with new-onset or relapsing/refractory GCA.
- •Westergren erythrocyte sedimentation rate > 30 mm/hour or c-reactive protein ≥ 1 mg/ dL.
- •Remission of GCA at or before Day
- •Female subjects must be postmenopausal or permanently sterile following documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation or having a male partner with vasectomy as affirmed by the subject, or nonpregnant, nonlactating, and if sexually active having agreed to use a highly effective method of contraception.
- •Male subjects must have documented vasectomy or if sexually active must agree to use a highly effective method of contraception with their partners of childbearing potential.
排除标准
- •Transplanted organs (except corneal transplant performed more than 3 months prior to randomization).
- •Concurrent enrollment in another interventional clinical study.
- •Treatment with non-biologic investigational drug therapy within 4 weeks or 5 half-lives of the study agent, whichever was longer, prior to screening.
- •Cell-depleting biological therapies within 12 months prior to Day 0, or noncell-depleting biological therapies within 8 weeks (or 5 half-lives, whichever is longer) prior to screening.
- •Treatment with alkylating agents within 12 weeks prior to screening.
- •Intramuscular, Intra-articular or IV corticosteroids within 4 weeks prior to screening.
- •Receipt of live (attenuated) vaccine within the 4 weeks before Day
- •Treatment with hydroxychloroquine, cyclosporine A, azathioprine, cyclophosphamide, or mycophenolate mofetil (MMF) within 4 weeks of screening.
- •Female subjects who are pregnant, intending to become pregnant, or are breastfeeding.
- •Known history of allergy or reaction to any component of the mavrilimumab or placebo formulation or to any other biologic therapy or prednisone or any of its excipients.
- •Positive (or 2 indeterminate) QuantiFERON test results.
- •Clinically significant active infection or infection requiring hospitalization or IV antibiotics within 12 weeks before screening or opportunistic infection within 6 months before screening.
- •Chronic active hepatitis B infection.
- •Subjects at a high risk of infection, a history of an infected joint prosthesis still in situ, leg ulcers, indwelling urinary catheter, or persistent or recurrent chest infections.
- •History of cancer within the last 10 years, except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured.
- •Evidence of clinically-uncontrolled respiratory disease.
- •History of chronic respiratory tract infections.
研究组 & 干预措施
mavrilimumab
Subjects randomized to mavrilimumab will receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
干预措施: mavrilimumab (Combination Product)
mavrilimumab
Subjects randomized to mavrilimumab will receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
干预措施: prednisone (Drug)
placebo
Subjects randomized to placebo will receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
干预措施: placebo (Combination Product)
placebo
Subjects randomized to placebo will receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
干预措施: prednisone (Drug)
结局指标
主要结局
Time to Flare by Week 26
时间窗: Week 26
Time to flare by Week 26 was defined as time from randomization to the date of first flare occurring within the 26-week period, as assessed by independent adjudication. Kaplan-Meier method used to estimate the survival functions for each treatment arm. Flare/relapse was defined as a C-reactive protein (CRP) of 1 mg/dL or greater and/or erythrocyte sedimentation rate (ESR) of 30 mm/h or greater AND at least one of the following signs or symptoms attributed to GCA: Cranial symptoms (new-onset localized headache; scalp or temporal artery tenderness; ischemic-related vision loss; unexplained mouth or jaw pain upon mastication; transient ischemic attack or stroke related to GCA); Extracranial symptoms (claudication of the extremities; symptoms of polymyalgia rheumatica); New or worsening angiographic abnormalities detected via MRI, CT/CTA, or PET-CT of the aorta or other great vessels or via ultrasound of the temporal arteries.
次要结局
- Cumulative Corticosteroid Dose at Week 26(Week 26)
- Percentage of Participants Who Completed the 26-Week Corticosteroid Taper and Who Had a Normal ESR(Week 26)
- Time to Elevated Erythrocyte Sedimentation Rate (ESR) by Week 26(Week 26)
- Percentage of Participants Who Completed the 26-week Corticosteroid Taper and Who Had No Signs or Symptoms of GCA Nor New or Worsening Vasculitis by Imaging by Week 26(Week 26)
- Sustained Remission Rate at Week 26(Week 26)
- Time to Elevated C-Reactive Protein (CRP) by Week 26(Week 26)
- Time to Signs/Symptoms of Giant Cell Arteritis (GCA) or New or Worsening Vasculitis on Imaging by Week 26(Week 26)
- Percentage of Participants Who Completed the 26-Week Corticosteroid Taper and Who Had a Normal CRP Level(Week 26)
- Cumulative Corticosteroid Dose at the End of the Washout Safety Follow-up Period(Final Safety Follow-up visit (Week 38))