study of efficacy, safety and tolerability of acz885 (canakinumab) in patients with pulmonary sarcoidosis

Conditions: Pulmonary Sarcoidosis

Summary: the purpose of this study is to assess if acz885 will improve lung function in association with reduction of tissue inflammation in patients with chronic sarcoidosis.


Eligibility criteria:
key inclusion criteria: * male and female subjects ages 18 to 80 years of age (both inclusive) * pulmonary sarcoidosis disease duration of ≥1 year * clinically active disease demonstrated either by a biopsy (any organ) or by bronchoalevolar lavage (lymphocytosis \>15%, cd4+/cd8+ ration\>3.5, cd103+/cd4+/cd4+ ratio \<0.2). patients must also have all of the following criteria: 1. mmrc dyspnea scale ≥1 2. threshold fvc 50 - 90% of predicted 3. evidence of parenchymal lung involvement by hrct at screening or by historical radiological evidence (e.g. ct, mri or x-ray) key exclusion criteria: * treated pulmonary hypertension * previous exposure to concomitant treatment according to the following criteria: 1. prednisone \>15 mg/day or changes in prednisone dose in the 8 weeks prior to screening 2. more than one immune-modulator (i.e., methotrexate, azathioprine, leflunomide, hydroxychloroquine) or changes in their dosing levels within 12 weeks of randomization. 3. mycophenolate use within 12 weeks of randomization * prior treatment with any biologic drug targeting the immune system within 180 days of randomization or history of any previous use of rituximab * history of bleeding disorder * forced vital capacity (fvc) \<50% of predicted * extra-pulmonary sarcoidosis as primary treatment indication (e.g., involving brain, heart, eye and renal disease with significant hypercalcemia) * any conditions or significant medical problems which in the opinion of the investigator immune-compromise the patient and/or places the patient at unacceptable risk for immunomodulatory therapy, such as: 1. absolute neutrophil count (anc) \<lln (1,500/μl) 2. thrombocytopenia ctcae v4.03 grade 1: platelets \<lln (75.0 x 10exp9/l) 3. any active or recurrent bacterial, fungal (with exception of onychomycosis) or viral infection 4. presence of human immunodeficiency virus (hiv) infection, hepatitis b or hepatitis c infections based on screening lab results 5. presence of active or latent tuberculosis (tb). if historical tb result is available, tb status needs to be confirmed pre-randomization as determined by screening laboratory measurements. 6. clinical evidence or history of multiple sclerosis or other demyelinating diseases, or felty's syndrome * live vaccinations within 3 months prior to the start of the trial * current severe progressive or uncontrolled disease which in the judgment of the clinical investigator renders the patient unsuitable for the trial * women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using methods of contraception defined in the protocol for the study.

Keywords: pulmonary sarcoidosis sarcoidosis canakinumab autoimmune diseases granulomas inflammation lung function testing immunosuppressive agents interleukin interleukin-1beta [f-18]fdg-pet/ct respiratory pulmonary steroids corticosteroids lung diseases