Phase 2 Randomized Trial of IVIg With or Without Cyclophosphamide in Pemphigus
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Clinical Outcome: Extent and Severity of Disease
研究概览
简要总结
The purpose of this study is to compare two standard treatments for pemphigus to determine which more effectively improves the clinical manifestations of the disease and decreases serum level of the autoantibodies which cause the disease.
详细描述
Pemphigus is a serious and life-threatening autoimmune disease characterized by blisters and erosions that occur on the skin and oral mucosa. It is caused by autoantibodies that attack desmoglein 1 and 3, adhesion molecules that are present on the surface of the cells (keratinocytes) that make up the superficial layer of the skin. As a result these cells stop sticking together, and come apart resulting in the formation of blisters on the skin.
Pemphigus is usually treated with systemic corticosteroids often given together with immunosuppressive drugs such as Cytoxan (cyclophosphamide), Imuran (azathioprine), methotrexate, CellCept (mycophenolate mofetil) and others. However, the prolonged and high doses of systemic steroids and other immunosuppressive agents used to treat the disease are associated with significant toxicity.
A new treatment which is now being used to treat pemphigus patients that are unresponsive, or that have developed complications to conventional treatment is IVIg (intravenous immunoglobulin). IVIg consists of one of the protein fractions present in blood. It is the fraction that contains antibodies and is called immunoglobulin (Ig). It is purified from blood that has been collected from thousands of donors and treated to remove potential infectious agents. It is administered intravenously (IV) over several hours, several days in succession. The cycles are usually repeated every 2 to 4 weeks until the disease is controlled.
IVIg treatment is currently given in either of two ways, either by itself or with an immunosuppressive drug such as cyclophosphamide or azathioprine. It is unknown which of these two procedures is better. This trial is being conducted to determine which treatment is more effective.
The trial is being conducted in patients with pemphigus that are not responding to, or have developed complications from, standard treatment. All patients will be treated with IVIg administered using a standard protocol. The IVIg will be given daily for 4 days, and this cycle will be repeated every other week for a total of 4 cycles. In addition, half of the patients will be selected by chance to also be treated with cyclophosphamide, an immunosuppressive drug often used to treat other autoimmune diseases including pemphigus. The cyclophosphamide is a pill that is taken 3 times a day. A total of 12 patients will be treated in each arm of the trial. The trial is being conducted by Dr. Jean-Claude Bystryn at the New York University Medical Center.
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
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Lesions consistent with pemphigus foliaceus or vulgaris
- •Diagnosis confirmed by histology and IIF ≥ 40 within past month
- •On ≥20mg/day of prednisone per day for two weeks or ≥ 80mg/day for one week
- •Women of childbearing potential negative HCG obtained two weeks prior to first IVIg
- •Agrees to two acceptable forms of contraception* if randomized to cyclophosphamide group:
- •IUD (except progesterone T), Combination oral contraceptives, transdermal patch, vaginal ring, hormonal injectables or implantables, male latex condom, diaphragm, cervical cap, or vaginal sponge (contains spermicide)
- •Normal organ function confirmed by CBC, UA, LFTs and Ig levels within defined inclusion criteria
- •Responds yes to at least one of the criteria below:
- •Persistence of clinical manifestations of disease despite steroid treatment
- •Flare in disease activity after an attempt at steroid tapering
- •Failure of established lesions to heal
- •Rapidly progressive disease.
- •Conventional therapy is relatively contraindicated i.e. side effects, co-morbid conditions
- •systemic infections, peptic ulcers, osteoporosis, hypertension, cataracts or others
排除标准
- •Use of IVIg within past 3 weeks or the use of a cytotoxic drug within the past 2 weeks
- •Participating in another clinical trial at the time of screening and enrollment
- •Medical condition that precludes use of IVIg or cyclophosphamide (i.e. pregnancy breastfeeding, underlying chronic infection, concurrent opportunistic infection, sepsis or volume depletion
- •Renal insufficiency ( GFR <90, proteinuria (>1+, x 2), creatinine >1.8 or increased WBC or RBCs which cannot be explained by cystitis.)
- •Known hypersensitivity to study drugs, IVIg or cyclophosphamide
研究组 & 干预措施
Group A
IVIg alone (intravenous immunoglobulin)
干预措施: intravenous immunoglobulin (Drug)
Group B
IVIg with cyclophosphamide
干预措施: intravenous immunoglobulin (Drug)
Group B
IVIg with cyclophosphamide
干预措施: cyclophosphamide (Drug)
结局指标
主要结局
Clinical Outcome: Extent and Severity of Disease
时间窗: 6 - 10 weeks after initiation of therapy
Serum Levels of Pemphigus Antibodies
时间窗: 6-10 weeks after initiation of therapy
次要结局
- Toxicity of Treatment: Measured in Renal Toxicity, Myelosuppression or Hepatic Toxicity(Throughout course of study)
- Ability to be Weaned Off Steroids(Measured 6 and 10 weeks after initiation of IVIg treatment)