Study of Efficacy, Safety and Tolerability of ACZ885 (Canakinumab) in Patients With Pulmonary Sarcoidosis
Condition: Pulmonary Sarcoidosis
MeSH terms: Sarcoidosis, Pulmonary; Sarcoidosis
Intervention: ACZ885; Placebo
Intervention description: ACZ885 will be administered subcutaneously to assigned study subjects once monthly for 6 months.; Placebo will be administered subcutaneously to assigned study subjects once monthly for 6 months.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
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

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.