Trial of Adalimumab in Progressive Sarcoidosis
Condition: Sarcoidosis
MeSH terms: Sarcoidosis
Intervention: Adalimumab
Intervention description: Subjects will give themselves a dose of Adalimumab at 40 mg/every week by subcutaneous injection for a total of 45 weeks.
Intervention MeSH terms: Adalimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Sarcoidosis; Humira; Adalimumab; Tumor Necrosis Factor Inhibitors

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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 1.

          -  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

        Exclusion Criteria:

          -  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.