Trial Outcomes & Findings for Study of Efficacy, Safety and Tolerability of ACZ885 (Canakinumab) in Patients With Pulmonary Sarcoidosis (NCT NCT02888080)
NCT ID: NCT02888080
Last Updated: 2021-10-04
Results Overview
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).
COMPLETED
PHASE2
40 participants
Baseline, Week 24
2021-10-04
Participant Flow
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
Participant milestones
| Measure |
ACZ885
ACZ885 (300 mg s.c. once monthly for 6 months)
|
Placebo
Placebo (s.c. once monthly for 6 months)
|
|---|---|---|
|
Overall Study
STARTED
|
20
|
20
|
|
Overall Study
COMPLETED
|
18
|
15
|
|
Overall Study
NOT COMPLETED
|
2
|
5
|
Reasons for withdrawal
| Measure |
ACZ885
ACZ885 (300 mg s.c. once monthly for 6 months)
|
Placebo
Placebo (s.c. once monthly for 6 months)
|
|---|---|---|
|
Overall Study
Subject / Guardian decision
|
1
|
3
|
|
Overall Study
New Therapy for study indication
|
1
|
0
|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
|
Overall Study
Adverse Event
|
0
|
1
|
Baseline Characteristics
Study of Efficacy, Safety and Tolerability of ACZ885 (Canakinumab) in Patients With Pulmonary Sarcoidosis
Baseline characteristics by cohort
| Measure |
ACZ885
n=20 Participants
ACZ885 (300 mg s.c. once monthly for 6 months)
|
Placebo
n=20 Participants
Placebo (s.c. once monthly for 6 months)
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51.9 years
STANDARD_DEVIATION 8.45 • n=5 Participants
|
48.1 years
STANDARD_DEVIATION 9.94 • n=7 Participants
|
50.0 years
STANDARD_DEVIATION 9.30 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
18 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 24Population: Pharmacodynamic Analysis Set, with measure
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).
Outcome measures
| Measure |
ACZ885
n=20 Participants
ACZ885 (300 mg s.c. once monthly for 6 months)
|
Placebo
n=20 Participants
Placebo (s.c. once monthly for 6 months)
|
|---|---|---|
|
Change Between Baseline and Week 24 in Pulmonary Function as Measured by Spirometry
|
-1.90 Percent Predicted Forced Vital Capacity
Standard Deviation 3.91
|
0.52 Percent Predicted Forced Vital Capacity
Standard Deviation 3.37
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Pharmacodynamic Analysis Set, with measure
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.
Outcome measures
| Measure |
ACZ885
n=20 Participants
ACZ885 (300 mg s.c. once monthly for 6 months)
|
Placebo
n=20 Participants
Placebo (s.c. once monthly for 6 months)
|
|---|---|---|
|
Change Between Baseline and Week 12 in Pulmonary Tissue Inflammation (Lung Parenchyma) as Measured by SUVmax[F-18]FDG-PET/CT
|
-4.48 percentage (Mean % Change In SUVmax)
Standard Deviation 37.45
|
4.07 percentage (Mean % Change In SUVmax)
Standard Deviation 26.61
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Pharmacodynamic Analysis Set, with measure
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.
Outcome measures
| Measure |
ACZ885
n=20 Participants
ACZ885 (300 mg s.c. once monthly for 6 months)
|
Placebo
n=20 Participants
Placebo (s.c. once monthly for 6 months)
|
|---|---|---|
|
Change Between Baseline and Week 12 in Nodular Uptake Regions as Measured by SUVmax[F-18]FDG-PET/CT
|
-7.70 percentage (Mean % Change In SUVmax)
Standard Deviation 35.77
|
1.03 percentage (Mean % Change In SUVmax)
Standard Deviation 41.10
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Pharmacodynamic Analysis Set, with measure
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.
Outcome measures
| Measure |
ACZ885
n=20 Participants
ACZ885 (300 mg s.c. once monthly for 6 months)
|
Placebo
n=20 Participants
Placebo (s.c. once monthly for 6 months)
|
|---|---|---|
|
Change Between Baseline and Week 12 in in the Extrathoracic Region as Measured by SUVmax[F-18]FDG-PET/CT
|
-21.4 percentage (Mean % Change In SUVmax)
Standard Deviation 13.15
|
1.76 percentage (Mean % Change In SUVmax)
Standard Deviation 39.60
|
SECONDARY outcome
Timeframe: Baseline, week 24Population: Pharmacodynamic Analysis Set, with measure
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
Outcome measures
| Measure |
ACZ885
n=20 Participants
ACZ885 (300 mg s.c. once monthly for 6 months)
|
Placebo
n=20 Participants
Placebo (s.c. once monthly for 6 months)
|
|---|---|---|
|
Change From Baseline in Other Parameters of Pulmonary Function Testing (FEV 1, 3, 6 Seconds and Predicted)
FEV in 1 Second
|
-0.06 Liter/second
Interval -0.12 to 0.01
|
0.05 Liter/second
Interval -0.202 to 0.12
|
|
Change From Baseline in Other Parameters of Pulmonary Function Testing (FEV 1, 3, 6 Seconds and Predicted)
FEV in 3 seconds
|
-0.08 Liter/second
Interval -0.15 to 0.01
|
0.04 Liter/second
Interval -0.04 to 0.11
|
|
Change From Baseline in Other Parameters of Pulmonary Function Testing (FEV 1, 3, 6 Seconds and Predicted)
FEV in 6 seconds
|
-0.08 Liter/second
Interval -0.15 to 0.01
|
0.04 Liter/second
Interval -0.03 to 0.11
|
|
Change From Baseline in Other Parameters of Pulmonary Function Testing (FEV 1, 3, 6 Seconds and Predicted)
Predicted FEV
|
-1.20 Liter/second
Interval -2.87 to 0.48
|
0.89 Liter/second
Interval -0.87 to 2.66
|
|
Change From Baseline in Other Parameters of Pulmonary Function Testing (FEV 1, 3, 6 Seconds and Predicted)
Forced Expiratory Flow 25-75%
|
-0.0 Liter/second
Interval -1.0 to 0.8
|
0.1 Liter/second
Interval -0.1 to 0.6
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Pharmacodynamic Analysis Set, with measure
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).
Outcome measures
| Measure |
ACZ885
n=20 Participants
ACZ885 (300 mg s.c. once monthly for 6 months)
|
Placebo
n=20 Participants
Placebo (s.c. once monthly for 6 months)
|
|---|---|---|
|
Change From Baseline in High Resolution Computed Tomography (HRCT) Scoring
Parameter (unit): Mean of Consolidation
|
0.11 score on a scale
Standard Error 0.21
|
0.00 score on a scale
Standard Error 0.24
|
|
Change From Baseline in High Resolution Computed Tomography (HRCT) Scoring
Parameter (unit): Mean of Fibrosis
|
0.14 score on a scale
Standard Error 0.20
|
-0.26 score on a scale
Standard Error 0.22
|
|
Change From Baseline in High Resolution Computed Tomography (HRCT) Scoring
Parameter (unit): Mean of Ground Glass Opacities
|
0.12 score on a scale
Standard Error 0.39
|
-0.21 score on a scale
Standard Error 0.43
|
|
Change From Baseline in High Resolution Computed Tomography (HRCT) Scoring
Parameter (unit): Mean of Linear Opacities
|
-0.08 score on a scale
Standard Error 0.04
|
-0.00 score on a scale
Standard Error 0.05
|
|
Change From Baseline in High Resolution Computed Tomography (HRCT) Scoring
Parameter (unit): Mean of Nodule
|
0.55 score on a scale
Standard Error 0.57
|
-0.46 score on a scale
Standard Error 0.63
|
|
Change From Baseline in High Resolution Computed Tomography (HRCT) Scoring
Parameter (unit): Mean of Total Sarcoidosis Score
|
0.47 score on a scale
Standard Error 1.04
|
-0.79 score on a scale
Standard Error 1.14
|
SECONDARY outcome
Timeframe: Baseline, Week 12, and Week 24Population: Pharmacodynamic Analysis Set, with measure
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
Outcome measures
| Measure |
ACZ885
n=20 Participants
ACZ885 (300 mg s.c. once monthly for 6 months)
|
Placebo
n=20 Participants
Placebo (s.c. once monthly for 6 months)
|
|---|---|---|
|
Change From Baseline Distance Walked as Assessed by the 6-minute Walk Test
Baseline
|
453.65 meter
Standard Deviation 98.643
|
502.36 meter
Standard Deviation 79.368
|
|
Change From Baseline Distance Walked as Assessed by the 6-minute Walk Test
Week 12
|
471.57 meter
Standard Deviation 85.623
|
510.39 meter
Standard Deviation 99.555
|
|
Change From Baseline Distance Walked as Assessed by the 6-minute Walk Test
Week 24
|
479.40 meter
Standard Deviation 95.212
|
511.74 meter
Standard Deviation 104.359
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: Pharmacodynamic Analysis Set, with measure
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
Outcome measures
| Measure |
ACZ885
n=20 Participants
ACZ885 (300 mg s.c. once monthly for 6 months)
|
Placebo
n=20 Participants
Placebo (s.c. once monthly for 6 months)
|
|---|---|---|
|
Change From Baseline of Additional [F-18]FDG-PET Outcomes
SUV mean lymph nodes
|
-12.1 Percentage of Change In SUVmean
Standard Error 8.09
|
-4.77 Percentage of Change In SUVmean
Standard Error 8.35
|
|
Change From Baseline of Additional [F-18]FDG-PET Outcomes
SUV mean lung parenchyma
|
-6.39 Percentage of Change In SUVmean
Standard Error 9.00
|
-3.87 Percentage of Change In SUVmean
Standard Error 9.30
|
|
Change From Baseline of Additional [F-18]FDG-PET Outcomes
SUV mean extra thoracic region
|
-9.75 Percentage of Change In SUVmean
Standard Error 15.23
|
-15.2 Percentage of Change In SUVmean
Standard Error 11.39
|
SECONDARY outcome
Timeframe: Baseline, week 24Population: Pharmacodynamic Analysis Set, with measure
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.
Outcome measures
| Measure |
ACZ885
n=20 Participants
ACZ885 (300 mg s.c. once monthly for 6 months)
|
Placebo
n=20 Participants
Placebo (s.c. once monthly for 6 months)
|
|---|---|---|
|
Change From Baseline in Other Parameters of Pulmonary Function Testing : Diffusion Capacity of Lung for CO
|
-0.85 mL/min/mmHg
Standard Deviation 1.740
|
-1.05 mL/min/mmHg
Standard Deviation 1.978
|
SECONDARY outcome
Timeframe: Baseline, week 24Population: Pharmacodynamic Analysis Set, with measure
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
Outcome measures
| Measure |
ACZ885
n=20 Participants
ACZ885 (300 mg s.c. once monthly for 6 months)
|
Placebo
n=20 Participants
Placebo (s.c. once monthly for 6 months)
|
|---|---|---|
|
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)
% Predicted DLco
|
-2.68 percentage
Standard Deviation 5.082
|
-2.71 percentage
Standard Deviation 5.028
|
|
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)
% FEV1/FVC
|
0.19 percentage
Standard Deviation 3.549
|
0.73 percentage
Standard Deviation 2.221
|
|
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)
% FEV3/FVC
|
-0.05 percentage
Standard Deviation 2.617
|
0.21 percentage
Standard Deviation 1.612
|
|
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)
%Predicted FEF25-75
|
-0.94 percentage
Standard Deviation 11.375
|
3.22 percentage
Standard Deviation 5.485
|
|
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)
% RV/TLC (Residual Volume /Total Lung Capacity)
|
0.63 percentage
Standard Deviation 3.106
|
0.23 percentage
Standard Deviation 3.243
|
Adverse Events
ACZ885 300 mg
Placebo
Serious adverse events
| Measure |
ACZ885 300 mg
n=20 participants at risk
ACZ885 300 mg
|
Placebo
n=20 participants at risk
Placebo (s.c. once monthly for 6 months)
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
5.0%
1/20 • 40 months
AE additional description
|
0.00%
0/20 • 40 months
AE additional description
|
|
Cardiac disorders
Coronary artery disease
|
5.0%
1/20 • 40 months
AE additional description
|
0.00%
0/20 • 40 months
AE additional description
|
|
Gastrointestinal disorders
Large intestine polyp
|
0.00%
0/20 • 40 months
AE additional description
|
5.0%
1/20 • 40 months
AE additional description
|
|
Infections and infestations
Appendicitis
|
0.00%
0/20 • 40 months
AE additional description
|
5.0%
1/20 • 40 months
AE additional description
|
|
Infections and infestations
Influenza
|
5.0%
1/20 • 40 months
AE additional description
|
0.00%
0/20 • 40 months
AE additional description
|
|
Infections and infestations
Peritonitis
|
0.00%
0/20 • 40 months
AE additional description
|
5.0%
1/20 • 40 months
AE additional description
|
|
Investigations
Atypical mycobacterium test positive
|
0.00%
0/20 • 40 months
AE additional description
|
5.0%
1/20 • 40 months
AE additional description
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/20 • 40 months
AE additional description
|
5.0%
1/20 • 40 months
AE additional description
|
Other adverse events
| Measure |
ACZ885 300 mg
n=20 participants at risk
ACZ885 300 mg
|
Placebo
n=20 participants at risk
Placebo (s.c. once monthly for 6 months)
|
|---|---|---|
|
Ear and labyrinth disorders
Ear pain
|
10.0%
2/20 • 40 months
AE additional description
|
0.00%
0/20 • 40 months
AE additional description
|
|
Gastrointestinal disorders
Diarrhoea
|
10.0%
2/20 • 40 months
AE additional description
|
10.0%
2/20 • 40 months
AE additional description
|
|
Gastrointestinal disorders
Nausea
|
10.0%
2/20 • 40 months
AE additional description
|
5.0%
1/20 • 40 months
AE additional description
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
2/20 • 40 months
AE additional description
|
5.0%
1/20 • 40 months
AE additional description
|
|
General disorders
Fatigue
|
30.0%
6/20 • 40 months
AE additional description
|
25.0%
5/20 • 40 months
AE additional description
|
|
Infections and infestations
Influenza
|
0.00%
0/20 • 40 months
AE additional description
|
10.0%
2/20 • 40 months
AE additional description
|
|
Infections and infestations
Nasopharyngitis
|
25.0%
5/20 • 40 months
AE additional description
|
30.0%
6/20 • 40 months
AE additional description
|
|
Infections and infestations
Pulpitis dental
|
0.00%
0/20 • 40 months
AE additional description
|
10.0%
2/20 • 40 months
AE additional description
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.0%
1/20 • 40 months
AE additional description
|
10.0%
2/20 • 40 months
AE additional description
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
10.0%
2/20 • 40 months
AE additional description
|
0.00%
0/20 • 40 months
AE additional description
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.0%
2/20 • 40 months
AE additional description
|
0.00%
0/20 • 40 months
AE additional description
|
|
Nervous system disorders
Dizziness
|
15.0%
3/20 • 40 months
AE additional description
|
0.00%
0/20 • 40 months
AE additional description
|
|
Nervous system disorders
Headache
|
20.0%
4/20 • 40 months
AE additional description
|
10.0%
2/20 • 40 months
AE additional description
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.0%
2/20 • 40 months
AE additional description
|
5.0%
1/20 • 40 months
AE additional description
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
15.0%
3/20 • 40 months
AE additional description
|
0.00%
0/20 • 40 months
AE additional description
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/20 • 40 months
AE additional description
|
10.0%
2/20 • 40 months
AE additional description
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER