Study of Efficacy, Safety and Tolerability of ACZ885 (Canakinumab) in Patients With Pulmonary Sarcoidosis
- Registration Number
- NCT02888080
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
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Male and female subjects ages 18 to 80 years of age (both inclusive)
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Pulmonary sarcoidosis disease duration of ≥1 year
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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:
- MMRC dyspnea scale ≥1
- Threshold FVC 50 - 90% of predicted
- Evidence of parenchymal lung involvement by HRCT at screening or by historical radiological evidence (e.g. CT, MRI or x-ray)
Key
-
Treated pulmonary hypertension
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Previous exposure to concomitant treatment according to the following criteria:
- Prednisone >15 mg/day or changes in prednisone dose in the 8 weeks prior to screening
- More than one immune-modulator (i.e., methotrexate, azathioprine, leflunomide, hydroxychloroquine) or changes in their dosing levels within 12 weeks of randomization.
- Mycophenolate use within 12 weeks of randomization
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Prior treatment with any biologic drug targeting the immune system within 180 days of randomization or history of any previous use of rituximab
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History of bleeding disorder
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Forced vital capacity (FVC) <50% of predicted
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Extra-pulmonary sarcoidosis as primary treatment indication (e.g., involving brain, heart, eye and renal disease with significant hypercalcemia)
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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:
- Absolute neutrophil count (ANC) <LLN (1,500/μl)
- Thrombocytopenia CTCAE v4.03 Grade 1: Platelets <LLN (75.0 x 10exp9/L)
- Any active or recurrent bacterial, fungal (with exception of onychomycosis) or viral infection
- Presence of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C infections based on screening lab results
- 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.
- Clinical evidence or history of multiple sclerosis or other demyelinating diseases, or Felty's syndrome
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Live vaccinations within 3 months prior to the start of the trial
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Current severe progressive or uncontrolled disease which in the judgment of the clinical investigator renders the patient unsuitable for the trial
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ACZ885 ACZ885 ACZ885 (300 mg/2 mL) will be administered subcutaneously to assigned study subjects once monthly for 6 months. Placebo Placebo Placebo (0 mg/2 mL) will be administered subcutaneously to assigned study subjects once monthly for 6 months.
- Primary Outcome Measures
Name Time Method Change Between Baseline and Week 24 in Pulmonary Function as Measured by Spirometry Baseline, Week 24 To compare the effect of ACZ885 versus placebo in the change between baseline and week 24 in pulmonary function as measured by spirometry (Predicted Forced Vital Capacity).
- Secondary Outcome Measures
Name Time Method Change Between Baseline and Week 12 in Pulmonary Tissue Inflammation (Lung Parenchyma) as Measured by SUVmax[F-18]FDG-PET/CT Baseline, Week 12 To determine the effect of ACZ885 on the change of pulmonary tissue inflammation as measured by SUVmax\[F-18\]FDG-PET/CT from baseline after 12 weeks of treatment compared to placebo.
Change Between Baseline and Week 12 in Nodular Uptake Regions as Measured by SUVmax[F-18]FDG-PET/CT Baseline, Week 12 To determine the effect of ACZ885 on decreasing the maximum standardized uptake value (SUVmax) \[F-18\]FDG-PET in nodules (nodular uptake regions) after 12 weeks of treatment, compared to placebo.
Change Between Baseline and Week 12 in in the Extrathoracic Region as Measured by SUVmax[F-18]FDG-PET/CT Baseline, Week 12 To determine the effect of ACZ885 on decreasing the maximum standardized uptake value (SUVmax) \[F-18\]FDG-PET in in the extrathoracic Region after 12 weeks of treatment, compared to placebo.
Change From Baseline in Other Parameters of Pulmonary Function Testing (FEV 1, 3, 6 Seconds and Predicted) Baseline, week 24 To determine the effect of ACZ885 versus placebo on other parameters of pulmonary function testing in patients with sarcoidosis at 24 weeks compared to baseline. Forced Expiratory Volume (FEV) in 1, 3, 6 seconds, predicted and forced expiratory flow 25-75%. Results expressed in change from baseline
Change From Baseline in High Resolution Computed Tomography (HRCT) Scoring Baseline, Week 24 To determine the effect of ACZ885 versus placebo on HRCT of patients with sarcoidosis at 24 weeks compared to initial HRCT scan as measured by side-by-side comparison by blinded reviewers and HRCT scoring. HRCT score : sum of total parameters scores, each measured in different lung zones (right upper lobe; left upper lobe; right middle lobe; right lower lobe; left lower lobe). The extent of the disease is assessed for each zone to the nearest 10% of parenchymal surface: 0 (no disease) to 10 (91-100% disease).
Change From Baseline Distance Walked as Assessed by the 6-minute Walk Test Baseline, Week 12, and Week 24 To determine the effect of ACZ885 versus placebo on the 6-minute walk test distance of patients with sarcoidosis at 12 and 24 weeks compared to baseline
Change From Baseline of Additional [F-18]FDG-PET Outcomes Baseline, Week 12 To determine the effect of ACZ885 on additional \[F-18\]FDG-PET outcomes after 12 weeks of treatment compared to placebo. SUVmean: Mean standard uptake value for activity in the focal region volume SUVpeak: Mean standardized uptake value of a sphere (a diamater of approximately 1.2cm - to produce a 1-cm3-volume spherical Region of Interest (ROI) that has the highest average SUV with the lesion volume
Change From Baseline in Other Parameters of Pulmonary Function Testing : Diffusion Capacity of Lung for CO Baseline, week 24 To determine the effect of ACZ885 versus placebo on other parameters of pulmonary function testing in patients with sarcoidosis at 24 weeks compared to baseline.
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) Baseline, week 24 To determine the effect of ACZ885 versus placebo on other parameters of pulmonary function testing in patients with sarcoidosis at 24 weeks compared to baseline. Percent Predicted DLco (Diffusion Capacity of Lung for CO), FEV1/FVC, FEV3/FVC (forced expiratory volume in 1 or 3 seconds /forced vital capacity), percent Predicted FEF25-75, RV/TLC
Trial Locations
- Locations (1)
Novartis Investigative Site
🇳🇱Rotterdam, Netherlands