A Prospective Open-Label Trial of Adalimumab in Progressive Sarcoidosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Change in FVC From Screening to Week 24
研究概览
简要总结
Sarcoidosis is a rare disease that can affect any organ in the body. It is characterized by the buildup of immune-system (fights off infection in the body) cells in organs. These cells form small groups called granulomas, which lead to inflammation of the surrounding tissue. Sarcoidosis most commonly affects the lung and the lymph nodes (part of the immune system). The signs usually include shortness of breath, fever, dry cough, and chest pain. Other signs in many patients can include redness and painful lumps on the skin, reduced eyesight, joint pain, and rarely, nervous system damage. Sarcoidosis commonly affects young and middle-aged adults.
There are no approved therapies for the treatment of sarcoidosis. Corticosteroid (steroid hormone) therapy is considered the standard treatment. Only limited benefit has been shown when using corticosteroid therapy to ease lung symptoms or improve lung function in patients with sarcoidosis. Also, the effects of other therapies (for example: methotrexate, cyclophosphamide, anti-malarial drugs, thalidomide) and other immunosuppressants (drugs that suppress a body's natural defense system [immune system]) which have been used in a small number of patients are not well known and can cause long term problems.
The drug used in this study is called adalimumab. Adalimumab is FDA (Food and Drug Administration) approved for patients with moderately to severely active rheumatoid arthritis. However, adalimumab is not approved for the treatment of sarcoidosis. Adalimumab is experimental in this study. The purpose of this study is to evaluate the safety and effectiveness of adalimumab in the treatment of patients with sarcoidosis with pulmonary (lung) involvement who show symptoms of the disease even though they are currently being treated with medication.
详细描述
This study consists of 11 visits (including screening).
Screening Procedures:
A chest radiograph (PA and lateral) must be obtained within 3 months prior to the first study injection. It must indicate that subject is free of tuberculosis (TB). The chest radiograph will also be used to confirm the stage of the disease.
Histologically proven sarcoidosis will be confirmed.
Demographic data, a complete medical history (including signs and symptoms of sarcoidosis), a physical examination (including vital signs, weight and height). The medical history will include questions about history of recent TB and history of close contact with persons who might have TB. Concomitant medications, including the use of oral corticosteroids and immunosuppressants, will be reviewed and recorded. In addition the inclusion and exclusion criteria will be reviewed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- 否
入选标准
- •Men and women > 18 years of age.
- •Sarcoidosis diagnosed at least 1 year prior to screening.
- •Histologically proven sarcoidosis prior to screening.
- •Have a diagnosis of sarcoidosis with evidence of parenchymal disease on chest radiograph (Stage II or III) or Stage I disease by chest radiographs and evidence of abnormal PFT as below or normal chest radiograph; or abnormal PFT, with abnormal chest computed tomography (CT) and evidence of sarcoid lung involvement by histology. Subjects with concurrent extrapulmonary sarcoidosis, particularly skin and eye involvement, are encouraged to be enrolled.
- •Have forced vital capacity (FVC) > 40 and < 80% of predicted.
- •Have an American Thoracic Society (ATS) dyspnea score of > Grade
- •Have been receiving pre-study treatment that includes at least 10 mg/day prednisone (or equivalent dose of corticosteroid) as a single agent, or 1 or more immunosuppressant (e.g., methotrexate, azathioprine, cyclophosphamide, chloroquine, leflunomide, hydroxychloroquine, mycophenolate mofetil, cyclosporine, tacrolimus, corticosteroids) for at least the 3-month period immediately prior to screening. Subjects must be on a stable dose of these medications for > 4 weeks before starting the study medication.
- •Adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) must be used for the duration of the study and such precautions should be continued for 6 months after receiving the last study agent injection.
- •Are considered eligible based on TB screening
排除标准
- •Have used any investigational drug within 1 month prior to screening.
- •Have received previous administration of a treatment with any other therapeutic agent targeted at reducing tumor necrosis factor [TNF] (e.g., pentoxifylline, thalidomide, etanercept, infliximab) within 3 months prior to screening.
- •Have received previous administration of adalimumab.
- •Have received any live virus or bacterial vaccinations within the 3 months before the first dose of the study agent or are expected to receive any live virus or bacterial vaccinations during the trial or up to 3 months after the last dose of the study agent.
- •Have had any previous adverse reactions or allergic reactions (e.g., anaphylaxis) associated with the administration of monoclonal antibodies.
- •Have New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF).
- •Have a history of severe right-sided heart failure or cor pulmonale.
- •Have had serious infections within 2 months of screening. Less serious infections (such as acute upper respiratory tract infection [colds] or a simple urinary tract infection) need not be considered as exclusion at the discretion of the investigator.
- •Are considered ineligible according to the United States of America (USA)-specific TB screening.
- •Have or have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis and aspergilloma, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening.
- •Have a known infection with human immunodeficiency virus (HIV).
- •Have current signs and symptoms of systemic lupus erythematosus, or severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, or cerebral diseases (with the exception of sarcoidosis).
- •Presence of a transplanted organ (with the exception of a corneal transplant) > 3 months prior to screening.
- •Have any known malignancy or history of malignancy within 5 years prior to screening.
- •Have a history of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease.
- •Are pregnant, nursing, or planning pregnancy (both men and women) during the trial or within the 6-month period thereafter.
- •Have had a known substance abuse or dependency, drug or alcohol within 3 years of screening.
- •Have poor tolerability of subcutaneous injection or lack of adequate venous access for required blood sampling.
- •Have a known history of demyelinating disease such as multiple sclerosis or optic neuritis.
- •Presence of a non-sarcoidosis condition affecting survival.
- •Have mental health problems interfering with participation.
研究组 & 干预措施
An open-label
Patients received adalimumab 40 mg weekly for 45 weeks, with a final follow-up at Week 52
干预措施: Adalimumab (Drug)
结局指标
主要结局
Change in FVC From Screening to Week 24
时间窗: 24 Weeks
The forced vital capacity (FVC) measurement shows the amount of air a person can forcefully and quickly exhale after taking a deep breath. Improvement in FVC, if significant, means better breathing and lung function. The change in FVC done at screening and at week 24 were compared to notice if there were any changes.
次要结局
- Change in Distance Walked During 6 Minute Walk Test at Screening and 24 Weeks(24 weeks)
- A Change in the Borg Dyspnea Score Before/After the 6 Minute Walk at Screening (S) and at 24 Weeks (W).(24 weeks)
- Physicians Global Assessment of Disease Activity.(24 weeks)
- Patient's Global Assessment of Disease Activity.(24 weeks)