Clinical trial NCT02888080: Study of Efficacy, Safety and Tolerability of ACZ885 (Canakinumab) in Patients With Pulmonary Sarcoidosis
Official title: A Multiple-dose, Subject and Investigator Blinded, Placebo-controlled, Parallel Design Study to Assess the Efficacy, Safety and Tolerability of ACZ885(Canakinumab) in Patients With Pulmonary Sarcoidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Sarcoidosis
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-09-02
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change Between Baseline and Week 24 in Pulmonary Function as Measured by Spirometry
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change Between Baseline and Week 12 in Pulmonary Tissue Inflammation (Lung Parenchyma) as Measured by SUVmax[F-18]FDG-PET/CT
timeFrame: Baseline, Week 12
measure: Change Between Baseline and Week 12 in Nodular Uptake Regions as Measured by SUVmax[F-18]FDG-PET/CT
timeFrame: Baseline, Week 12
measure: Change Between Baseline and Week 12 in in the Extrathoracic Region as Measured by SUVmax[F-18]FDG-PET/CT
timeFrame: Baseline, Week 12
measure: Change From Baseline in Other Parameters of Pulmonary Function Testing (FEV 1, 3, 6 Seconds and Predicted)
timeFrame: Baseline, week 24
measure: Change From Baseline in High Resolution Computed Tomography (HRCT) Scoring
timeFrame: Baseline, Week 24
measure: Change From Baseline Distance Walked as Assessed by the 6-minute Walk Test
timeFrame: Baseline, Week 12, and Week 24
measure: Change From Baseline of Additional [F-18]FDG-PET Outcomes
timeFrame: Baseline, Week 12
measure: Change From Baseline in Other Parameters of Pulmonary Function Testing : Diffusion Capacity of Lung for CO
timeFrame: Baseline, week 24
measure: Change From Baseline in Other Parameters of Pulmonary Function Testing : Percent Predicted DLco, FEV1/FVC, FEV3/FVC, Percent Predicted Forced Expiratory Flow (FEF) 25-75, RV/TLC (Residual Volume /Total Lung Capacity)
timeFrame: Baseline, week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Albany
country: United States
facility: Novartis Investigative Site
state: New York
city: Cleveland
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Nieuwegein
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
Study officials:
References: