A Phase 1b, Randomized, Double-Blind, Placebo Controlled Study With an Open Label Extension to Evaluate the Safety and Tolerability of Omalizumab, A Humanized IgG1 Monoclonal Antibody in Patients With Lupus (STOP LUPUS)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Safety of omalizumab in patients with SLE.
研究概览
简要总结
Background:
- Systemic Lupus Erythematosus (SLE or lupus) is an autoimmune disease, which means the body's immune system mistakenly attacks healthy tissue resulting in inflammation and tissue damage. SLE can involve almost any organ and its symptoms can range in severity from mild to life-threatening; symptoms also vary from person to person. Current treatments for lupus are not effective for some people. Medications used to treat lupus can have serious side effects.
- Omalizumab is a drug that has been used to treat severe allergic asthma. It helps to prevent allergic reactions by reducing some antibodies in the blood. These antibodies are also present in some people with Lupus. Researchers want to see if omalizumab is a safe and effective treatment for people with Lupus.
Objectives:
- To test the safety of omalizumab for people with lupus.
Eligibility:
- Individuals at least 18 years of age who have moderately active Lupus even with standard treatments.
Design:
- Subject screening will take place at the NIH Clinical Center and will include a medical history, a physical exam, blood and urine laboratory tests, an assessment of Lupus disease activity. Some participants may require some additional testing. All eligible persons who are interested in enrolling will be asked to come back to the NIH within 2 weeks to begin the study.
- The study will be conducted in three phases, with a total of 15 study visits over 38 weeks. Two visits will be overnight hospital stays. The rest will be outpatient visits. During each visit the participants will be monitored by doing a physical exam, assessment of their lupus disease activity, review of any treatment related side effects, blood and urine testing.
- For the first phase, participants will have infusions (under their skin) of either omalizumab or a placebo. They will have an overnight hospital stay for the first infusion and then an outpatient safety monitor visit 2 weeks after. If subjects safety measures are good they will return in 2 weeks and receive the second dose. They will then get three more doses every 4 weeks which will be given during outpatient visits to the NIH.
- In the second phase, which begins at the 16th week of the study, all participants will receive omalizumab. This means that subjects who had been getting omalizumab will continue receiving it and subjects who had been receiving the placebo will now begin getting omalizumab. They will have an overnight hospital stay for this infusion and will return in 2 weeks for a safety monitor visit. If subjects safety measures are good they will return in 2 weeks and receive the next dose. They will then get three more doses every 4 weeks which will be given during outpatient visits to the NIH.
- The third phase will be a final series of visits which will take place at week 32 and week 36. During these visits subjects will have a physical exam which includes disease activity assessment, blood and urine tests. No medication will be given during these visits.
- All subjects will be given information, instruction and medications for possible allergic reactions to omalizumab.
- Throughout the study other tests and procedures will be performed as needed.
详细描述
Background:
The immune system in systemic lupus erythematosus is characterized by abnormal activation of various cell types, such as T and B lymphocytes, macrophages and dendritic cells and the production of autoantibodies against nuclear antigens. Until recently most of the pathogenic autoantibodies were thought to be IgG antibodies. We have recently shown that Lyn deficient mice develop a lupus nephritis-like disease which is mediated by basophils activated by IgE autoantibodies. Moreover, SLE patients also have elevated serum self reactive IgEs, and activated basophils that express the lymph node homing molecule CD62L and the MHC Class II molecule, HLA-DR; markers that are associated with increased disease activity. Follow up studies confirmed an association of IgE anti-dsDNA antibodies with active SLE using a SLEDAI score of 4 as a cutoff (unpublished). In addition, we have also observed a strong correlation of IgE dsDNA antibodies with hypocomplementemia strongly suggesting that these autoantibodies are serologic markers of immune activation in SLE. Based on these observations we propose that depleting IgE (including IgE autoantibodies) may lead to improvement in SLE by reducing IgE-induced basophil activation.
Omalizumab is a humanized IgG1 monoclonal antibody against human IgE. It is approved by the FDA for the treatment of asthma. Omalizumab was shown to effectively deplete circulating IgE and decrease basophil action. In this study we propose to assess the safety of omalizumab in moderately active lupus patients and to assess its effect on circulating IgE autoantibodies and basophil activation. We will also collect preliminary data about its clinical efficacy.
Primary Objective:
To determine if omalizumab is tolerated in patients with Systemic Lupus Erythematosus.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
1
Subjects who were randomized to the placebo arm originally will receive 600 mg omalizumab by subcutaneous injection
干预措施: Omalizumab (Drug)
2
Subjects in the omalizumab arm will receive 300 mg omalizumab by subcutaneous injection in a doubleblinded fashion
干预措施: Omalizumab (Drug)
结局指标
主要结局
Safety of omalizumab in patients with SLE.
时间窗: Outcome measure are assessed once the last participant completes the last visit.
The primary outcome is to evaluate the safety and tolerance of omalizumab in patients with SLE. This analysis will include rates ofadverse events (serious adverse events, Grade 3 and 4 toxicities not fulfilling the criteria for SAE, and nonserious adverse events).
次要结局
- Reduced free IgE autoantibody levels. Decreased basophil activation. Reduced IgG autoantibody levels. Pharmacodynamics. Clinical efficacy.(Outcome measure are assessed once the last participant completes the last visit.)