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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ACZ885 | Experimental | ACZ885 (300 mg/2 mL) will be administered subcutaneously to assigned study subjects once monthly for 6 months. |
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| Placebo | Placebo Comparator | Placebo (0 mg/2 mL) will be administered subcutaneously to assigned study subjects once monthly for 6 months. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ACZ885 | Drug | ACZ885 will be administered subcutaneously to assigned study subjects once monthly for 6 months. |
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| Measure | Description | Time Frame |
|---|---|---|
| Change Between Baseline and Week 24 in Pulmonary Function as Measured by Spirometry | 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). | Baseline, Week 24 |
| 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 | 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. | Baseline, Week 12 |
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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:
Key Exclusion Criteria:
Treated pulmonary hypertension
Previous exposure to concomitant treatment according to the following criteria:
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:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Birmingham | Alabama | 35294-0006 | United States | ||
| Novartis Investigative Site |
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| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on novartisclinicaltrials.com | View source |
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Safety Analysis set : 20 patients ACZ885 and 20 patients Placebo
PK Analysis set : 20 patients ACZ885
PD Analysis set : 20 patients CAZ885 and 20 patients placebo
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| ID | Title | Description |
|---|---|---|
| FG000 | ACZ885 | ACZ885 (300 mg s.c. once monthly for 6 months) |
| FG001 | Placebo | Placebo (s.c. once monthly for 6 months) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 12, 2017 | Mar 2, 2020 |
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| Placebo | Drug | Placebo will be administered subcutaneously to assigned study subjects once monthly for 6 months. |
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| Change Between Baseline and Week 12 in Nodular Uptake Regions as Measured by SUVmax[F-18]FDG-PET/CT |
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. |
| Baseline, Week 12 |
| Change Between Baseline and Week 12 in in the Extrathoracic Region as Measured by SUVmax[F-18]FDG-PET/CT | 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. | Baseline, Week 12 |
| Change From Baseline in Other Parameters of Pulmonary Function Testing (FEV 1, 3, 6 Seconds and Predicted) | 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 | Baseline, week 24 |
| Change From Baseline in High Resolution Computed Tomography (HRCT) Scoring | 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). | Baseline, Week 24 |
| Change From Baseline Distance Walked as Assessed by the 6-minute Walk Test | 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 | Baseline, Week 12, and Week 24 |
| Change From Baseline of Additional [F-18]FDG-PET Outcomes | 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 | Baseline, Week 12 |
| Change From Baseline in Other Parameters of Pulmonary Function Testing : Diffusion Capacity of Lung for CO | 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. | Baseline, week 24 |
| 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) | 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 | Baseline, week 24 |
| Albany |
| New York |
| 12208 |
| United States |
| Novartis Investigative Site | Cleveland | Ohio | 44195 | United States |
| Novartis Investigative Site | Essen | 45147 | Germany |
| Novartis Investigative Site | Frankfurt | 60596 | Germany |
| Novartis Investigative Site | Hanover | 30625 | Germany |
| Novartis Investigative Site | Nieuwegein | 3435 CM | Netherlands |
| Novartis Investigative Site | Rotterdam | 3015 CE | Netherlands |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | ACZ885 | ACZ885 (300 mg s.c. once monthly for 6 months) |
| BG001 | Placebo | Placebo (s.c. once monthly for 6 months) |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Race | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change Between Baseline and Week 24 in Pulmonary Function as Measured by Spirometry | 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). | Pharmacodynamic Analysis Set, with measure | Posted | Mean | Standard Deviation | Percent Predicted Forced Vital Capacity | Baseline, Week 24 |
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| Secondary | Change Between Baseline and Week 12 in Pulmonary Tissue Inflammation (Lung Parenchyma) as Measured by SUVmax[F-18]FDG-PET/CT | 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. | Pharmacodynamic Analysis Set, with measure | Posted | Mean | Standard Deviation | percentage (Mean % Change In SUVmax) | Baseline, Week 12 |
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| Secondary | Change Between Baseline and Week 12 in Nodular Uptake Regions as Measured by SUVmax[F-18]FDG-PET/CT | 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. | Pharmacodynamic Analysis Set, with measure | Posted | Mean | Standard Deviation | percentage (Mean % Change In SUVmax) | Baseline, Week 12 |
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| Secondary | Change Between Baseline and Week 12 in in the Extrathoracic Region as Measured by SUVmax[F-18]FDG-PET/CT | 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. | Pharmacodynamic Analysis Set, with measure | Posted | Mean | Standard Deviation | percentage (Mean % Change In SUVmax) | Baseline, Week 12 |
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| Secondary | Change From Baseline in Other Parameters of Pulmonary Function Testing (FEV 1, 3, 6 Seconds and Predicted) | 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 | Pharmacodynamic Analysis Set, with measure | Posted | Median | 90% Confidence Interval | Liter/second | Baseline, week 24 |
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| Secondary | Change From Baseline in High Resolution Computed Tomography (HRCT) Scoring | 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). | Pharmacodynamic Analysis Set, with measure | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, Week 24 |
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| Secondary | Change From Baseline Distance Walked as Assessed by the 6-minute Walk Test | 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 | Pharmacodynamic Analysis Set, with measure | Posted | Mean | Standard Deviation | meter | Baseline, Week 12, and Week 24 |
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| Secondary | Change From Baseline of Additional [F-18]FDG-PET Outcomes | 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 | Pharmacodynamic Analysis Set, with measure | Posted | Least Squares Mean | Standard Error | Percentage of Change In SUVmean | Baseline, Week 12 |
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| Secondary | Change From Baseline in Other Parameters of Pulmonary Function Testing : Diffusion Capacity of Lung for CO | 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. | Pharmacodynamic Analysis Set, with measure | Posted | Mean | Standard Deviation | mL/min/mmHg | Baseline, week 24 |
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| Secondary | 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) | 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 | Pharmacodynamic Analysis Set, with measure | Posted | Mean | Standard Deviation | percentage | Baseline, week 24 |
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40 months
AE additional description
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ACZ885 300 mg | ACZ885 300 mg | 0 | 20 | 3 | 20 | 15 | 20 |
| EG001 | Placebo | Placebo (s.c. once monthly for 6 months) | 0 | 20 | 4 | 20 | 14 | 20 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
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| Coronary artery disease | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
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| Large intestine polyp | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
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| Appendicitis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
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| Peritonitis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
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| Atypical mycobacterium test positive | Investigations | MedDRA (21.1) | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ear pain | Ear and labyrinth disorders | MedDRA (21.1) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (21.1) | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
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| Pulpitis dental | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
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| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
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The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | novartis.email@novartis.com |
| Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 16, 2019 | Mar 2, 2020 | SAP_000.pdf |
| ID | Term |
|---|---|
| D017565 | Sarcoidosis, Pulmonary |
| D012507 | Sarcoidosis |
| D001327 | Autoimmune Diseases |
| D006099 | Granuloma |
| D007249 | Inflammation |
| D008171 | Lung Diseases |
| ID | Term |
|---|---|
| D017563 | Lung Diseases, Interstitial |
| D012140 | Respiratory Tract Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006968 | Hypersensitivity, Delayed |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C541220 | canakinumab |
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| White |
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| Asian |
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| Other |
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