Autoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis (ART-IPF)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 7
- 主要终点
- Autoantibodies to Human Epidermoid (HEp)-2 Cells
研究概览
简要总结
Recent research studies have suggested that proteins called antibodies that are produced by the immune system might be involved in the lung damage of idiopathic pulmonary fibrosis (IPF). Antibodies produced by the immune system normal help to fight infections by attacking bacteria and viruses without harming our own tissues. In patients with IPF, there is evidence that certain antibodies (called autoantibodies) attack the lung and contributes to the injury and scarring that occurs in IPF. Our recent studies have found that many IPF patients appear to have excessive autoantibody levels in blood and lungs that might make their disease worse.
Rituximab is a medication approved by the Food and Drug Administration (FDA) for the treatment of autoantibody diseases such as rheumatoid arthritis. Rituximab works by destroying B cells, a type of white blood cell, called a B-lymphocyte, which produce autoantibodies. In this research study, rituximab will be given into a vein to reduce the autoantibody levels that we believe might be contributing to the lung damage in IPF.
This study is being conducted to determine if rituximab provides beneficial effects for IPF patients by decreasing further lung injury.
详细描述
This is a double-blinded, Phase II trial in which 58 ambulatory IPF patients at any of four medical centers (University of Pittsburgh, University of Chicago, Geisinger Medical Center, and Temple University) will be randomized equally to 1. placebo or 2. two doses of rituximab 1 gm i.v., with a 14 day interval inbetween doses.
Subjects will be followed for 9 months.
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
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ambulatory patients with a diagnosis of IPF, not established >5 years from the enrollment date, that fulfills American Thoracic Society (ATS)/European Thoracic Society (ETS) Consensus Criteria.
- •Ability and willingness to give informed consent. Presence of autoantibodies against Hepatoma-2 (HEp-2) cells, the assay for the primary endpoint.
- •Age 50-85 y.o.
排除标准
- •Diagnoses of current infection, proven or suspected by participating physicians based upon their clinical assessments.
- •Presence of active hepatitis B or C, or HIV infection. Presence of positive CONVENTIONAL autoimmune serologic tests, e.g., Antinuclear Antibodies (ANA), Rheumatoid Factor (RF), Anti-Ro, Anti-LA, Anti-Ribonucleoprotein Antibodies (RNP), Anti-Jo-
- •History of reaction to murine-derived products or any of the trial medications, or prior exposures to human-murine chimeric antibodies.
- •Malignancy, excluding basal or squamous cell skin cancer and low-risk prostate cancer, defined as stage T1 or T2a with Prostate-Specific Antigen (PSA) less than 10 ng/dl.
- •Unwillingness to complete post-treatment surveillance for 9 months. Diagnosis of major morbidities (aside from IPF) expected to interfere with subjects' study participation for 9 months.
- •Treatment for >5 days within the preceding month with >10 mg. prednisone (or equivalent corticosteroid) or any treatment during the preceding month with a potent cellular immunosuppressant (e.g., cyclophosphamide, methotrexate, mycophenolate, azathioprine, calcineurin inhibitors, etc.).
- •Uncontrolled diabetes or hypertension that preclude safe treatment with methylprednisolone.
- •Concurrent participation in other experimental trials.
- •Pregnancy or unwillingness to use contraception during the duration of the study among female participants with child-bearing potential.
- •Ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) <70% of predicted values.
研究组 & 干预措施
Rituximab
Rituximab i.v. given on two occasions, with 14 days between doses.
干预措施: Rituximab (Drug)
Placebo
These subjects will receive i.v. placebo (5% dextrose in water) administered identically to the rituximab.
干预措施: Placebo (Drug)
结局指标
主要结局
Autoantibodies to Human Epidermoid (HEp)-2 Cells
时间窗: baseline to 9 months
Titers of anti-HEp-2 autoantibodies, by indirect immunofluorescence assays (IFA) over 9 months, month 9 reported. Titers represent the highest dilution of patient plasma wherein the autoantibodies can be detected. Higher titers denote greater autoantibody concentrations.
次要结局
- Changes in Forced Vital Capacity (FVC)(baseline thru 9 months)
- Number of Acute Exacerbations(during the study duration of 9 months)
- Changes in Anti-Heat Shock Protein 70 (HSP70) Autoantibodies(baseline to 9 months)
- Absolute Survival Percentage(during 9 months of observation)
- Number of Adverse Events (AE)(during the 9 months of observation)
- Transplant-Free Survival(during 9 months of observation)
- Hospitalizations(during 9 months of observation)
研究者
Steven R. Duncan, MD
Priniciple Investigator
University of Alabama at Birmingham