- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02888080
Study of Efficacy, Safety and Tolerability of ACZ885 (Canakinumab) in Patients With Pulmonary Sarcoidosis
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 Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Essen, Germany, 45147
- Novartis Investigative Site
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Frankfurt, Germany, 60596
- Novartis Investigative Site
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Hannover, Germany, 30625
- Novartis Investigative Site
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Nieuwegein, Netherlands, 3435 CM
- Novartis Investigative Site
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Rotterdam, Netherlands, 3015 CE
- Novartis Investigative Site
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Alabama
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Birmingham, Alabama, United States, 35294-0006
- Novartis Investigative Site
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New York
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Albany, New York, United States, 12208
- Novartis Investigative Site
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Ohio
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Cleveland, Ohio, United States, 44195
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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:
- 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 Exclusion Criteria:
- Treated pulmonary hypertension
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
- 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:
- 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
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: ACZ885
ACZ885 (300 mg/2 mL) will be administered subcutaneously to assigned study subjects once monthly for 6 months.
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ACZ885 will be administered subcutaneously to assigned study subjects once monthly for 6 months.
Other Names:
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Placebo Comparator: Placebo
Placebo (0 mg/2 mL) will be administered subcutaneously to assigned study subjects once monthly for 6 months.
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Placebo will be administered subcutaneously to assigned study subjects once monthly for 6 months.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change Between Baseline and Week 24 in Pulmonary Function as Measured by Spirometry
Time Frame: Baseline, Week 24
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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).
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Baseline, Week 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change Between Baseline and Week 12 in Pulmonary Tissue Inflammation (Lung Parenchyma) as Measured by SUVmax[F-18]FDG-PET/CT
Time Frame: Baseline, Week 12
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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.
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Baseline, Week 12
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Change Between Baseline and Week 12 in Nodular Uptake Regions as Measured by SUVmax[F-18]FDG-PET/CT
Time Frame: Baseline, Week 12
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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.
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Baseline, Week 12
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Change Between Baseline and Week 12 in in the Extrathoracic Region as Measured by SUVmax[F-18]FDG-PET/CT
Time Frame: Baseline, Week 12
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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.
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Baseline, Week 12
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Change From Baseline in Other Parameters of Pulmonary Function Testing (FEV 1, 3, 6 Seconds and Predicted)
Time Frame: Baseline, week 24
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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
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Baseline, week 24
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Change From Baseline in High Resolution Computed Tomography (HRCT) Scoring
Time Frame: Baseline, Week 24
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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).
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Baseline, Week 24
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Change From Baseline Distance Walked as Assessed by the 6-minute Walk Test
Time Frame: Baseline, Week 12, and Week 24
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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
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Baseline, Week 12, and Week 24
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Change From Baseline of Additional [F-18]FDG-PET Outcomes
Time Frame: Baseline, Week 12
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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
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Baseline, Week 12
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Change From Baseline in Other Parameters of Pulmonary Function Testing : Diffusion Capacity of Lung for CO
Time Frame: Baseline, week 24
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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.
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Baseline, week 24
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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)
Time Frame: Baseline, week 24
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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
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Baseline, week 24
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CACZ885X2205
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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