Study of Efficacy, Safety and Tolerability of ACZ885 (Canakinumab) in Patients With Pulmonary Sarcoidosis

Novartis

Status and phase: Completed; Phase 2

Conditions: Pulmonary Sarcoidosis

Treatments: Drug: ACZ885; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02888080

CACZ885X2205

Details and patient eligibility

About

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.

Enrollment: 40 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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40 participants in 2 patient groups, including a placebo group

ACZ885

Experimental group

Description:

ACZ885 (300 mg/2 mL) will be administered subcutaneously to assigned study subjects once monthly for 6 months.

Treatment:

Drug: ACZ885

Placebo

Placebo Comparator group

Description:

Placebo (0 mg/2 mL) will be administered subcutaneously to assigned study subjects once monthly for 6 months.

Treatment:

Drug: Placebo