Calprotectin-Directed Humira® Maintenance Therapy, a Double-blind, Double-dummy, Randomized Controlled Trial in Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Percent Time in Remission (PTIR) in PRNLOAD vs. Placebo arms
研究概览
简要总结
This is a study that invites adults with Crohn's disease and have been responding well to Adalimumab (Humira ®) for at least 6 months. Patients frequently discontinue maintenance medications in Crohn's disease, particularly when in remission. Patients want to know that they truly need to take a medication, yet they don't want to have flares. The purpose of this study is to see that if we monitor the patient, along with looking at changes in their stool samples, we can safely stop the maintenance medication Adalimumab for up to 48 weeks, or add as-needed dosing only, and keep them in remission.
详细描述
Patients frequently discontinue maintenance medications in Crohn's disease, particularly when in remission. Patients want to know that they truly need to take a medication, yet they don't want to have flares. As a biomarker, fecal calprotectin < 167 has a 100% negative predictive value for flare within the next 12 weeks (Gisbert, 2009). Adalimumab has low antigenicity, and can be safely stopped and restarted later with good clinical effect (Colombel, 2007). Patients want intermittent therapy, if it can be delivered in a timely fashion when pre-clinical inflammation starts, in order to avoid clinically-significant flares. This study will combine monitoring for pre-clinical inflammation with fecal calprotectin and as-needed dosing with Adalimumab to maintain remission in patients who have obtained remission with Adalimumab. This will be compared to two comparator arms: standard maintenance therapy and complete cessation of therapy (Step-Down approach).
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men or women 18 years of age or older at the time of informed consent.
- •Crohn's disease confirmed by endoscopy with biopsies.
- •On maintenance Adalimumab at a dose of 40 mg SC q 2 weeks without concomitant immunosuppressive therapy.
- •Must be in clinical remission (CDAI <150) at the baseline/randomization (Week 0) visit and biologic remission (both CRP <0.8 and FCP <167)at Week
- •Prior medication for Crohn's disease may include one of the following and must have been stopped with wash out periods: Methotrexate, Azathioprine, 6-Mercaptopurine, Tacrolimus, Steroids.
- •Negative for TB, Hepatitis B-negative, and negative stool for Clostridium difficile.
- •Exclusion Criteria
- •Unable to consent for themselves.
- •Are prisoners, students or employees of the investigators, or mentally incapacitated.
- •Are unwilling to complete this 48 week study, provide stool samples throughout, or unwilling to undergo multiple venipunctures.
- •Have a current infection with Clostridium difficile, clinically-significant intestinal stricture, history of allergy, or adverse reaction, to Adalimumab, history of sensitivity to latex.
- •Are currently using steroids or systemic immunomodulators (MTX, AZA, 6-MP, or Tacrolimus), or have used another biologic medication in the past 12 weeks other than Adalimumab, or have current or past use of Kineret® (Anakinra) or Tysabri® (natalizumab).
- •Have received any live bacterial or viral vaccinations ≤ 12 weeks prior to Week 0 and must not receive 12 months after study as well as BCG vaccination
- •Are known to have congestive heart failure.
- •Have a history of, or ongoing chronic or recurrent infectious disease, including but not limited to chronic renal, chest infection (i.e. bronchiectasis) or urinary tract infection (i.e. recurrent pyelonephritis) or open, draining, or infected skin wounds or ulcers.
- •Have evidence of current clinically active and important infection.
- •Have or ever had a non-tuberculous mycobacterium infection or serious opportunistic infection (i.e. cytomegalovirus, Pneumocystis carinii, aspergillosis).
- •Are known to be infected with HIV, Hepatitis B, or Hepatitis C.
- •Have severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease, or signs and symptoms thereof.
- •Have a known history of lymphoproliferative disease including lymphoma. Have a history of certain malignancies within five years of screening.
排除标准
- 未提供
研究组 & 干预措施
Placebo/Step-Down
1 syringe of placebo SC q 2 weeks.
干预措施: Placebo (Drug)
PRNLOAD Arm
160 mg/80 mg Adalimumab at Weeks 0 and 2, followed by 1 syringe SC placebo q 2 weeks (except at Weeks 12/14, 24/26, and 36/38)
干预措施: Adalimumab PRN (Drug)
Maintenance Arm
Adalimumab 40 mg q 2 weeks.
干预措施: Adalimumab (Drug)
结局指标
主要结局
Percent Time in Remission (PTIR) in PRNLOAD vs. Placebo arms
时间窗: 48 weeks
Determine whether adding as-needed q 12 weeks Adalimumab re-loading (160 mg/80 mg) when FCP ≥167 mcg/gram of stool can improve the maintenance of remission in Crohn's disease patients who stop Adalimumab therapy (PRNLOAD Arm) compared to the placebo arm. Endpoint: Percent time in remission (q 4 week evaluation for 48 weeks).
次要结局
- Strict Biologic Remission Rates(48 weeks)
- Subject acceptability(48 weeks)
- Subject preference(48 weeks)
- Equivalence of Percent Time in Remission(48 weeks)
- Comparison of Average CDAI(48 weeks)
- Comparison of average IBDQ(48 weeks)
- Comparison of average FCP(48 weeks)
- Comparison of average CRP(48 weeks)
- Comparison of Rates of Hospitalization(48 Weeks)
- Comparison of Rates of Emergency Department visits(48 Weeks)
- Comparison of Rates of Physician visits(48 Weeks)
- Percent Time in Remission MAINT vs. PRNLOAD(48 weeks)
- Percent Time in Remission MAINT vs. PBO(48 weeks.)
- Comparison of mg prednisone prescribed(48 Weeks)
研究者
Peter Higgins
M.D., Ph.D., MSc. Assistant Professor of Medicine
University of Michigan