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Study of Efficacy, Safety and Tolerability of ACZ885 (Canakinumab) in Patients With Pulmonary Sarcoidosis

Primary Purpose

Pulmonary Sarcoidosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ACZ885
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Sarcoidosis focused on measuring 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

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

ACZ885

Placebo

Arm Description

ACZ885 (300 mg/2 mL) will be administered subcutaneously to assigned study subjects once monthly for 6 months.

Placebo (0 mg/2 mL) will be administered subcutaneously to assigned study subjects once monthly for 6 months.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.
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.
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.
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
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).
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
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
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.
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

Full Information

First Posted
August 16, 2016
Last Updated
September 30, 2021
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02888080
Brief Title
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

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
December 19, 2016 (Actual)
Primary Completion Date
March 4, 2019 (Actual)
Study Completion Date
March 4, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ACZ885
Arm Type
Experimental
Arm Description
ACZ885 (300 mg/2 mL) will be administered subcutaneously to assigned study subjects once monthly for 6 months.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo (0 mg/2 mL) will be administered subcutaneously to assigned study subjects once monthly for 6 months.
Intervention Type
Drug
Intervention Name(s)
ACZ885
Other Intervention Name(s)
Canakinumab
Intervention Description
ACZ885 will be administered subcutaneously to assigned study subjects once monthly for 6 months.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo will be administered subcutaneously to assigned study subjects once monthly for 6 months.
Primary Outcome Measure Information:
Title
Change Between Baseline and Week 24 in Pulmonary Function as Measured by Spirometry
Description
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).
Time Frame
Baseline, Week 24
Secondary Outcome Measure Information:
Title
Change Between Baseline and Week 12 in Pulmonary Tissue Inflammation (Lung Parenchyma) as Measured by SUVmax[F-18]FDG-PET/CT
Description
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.
Time Frame
Baseline, Week 12
Title
Change Between Baseline and Week 12 in Nodular Uptake Regions as Measured by SUVmax[F-18]FDG-PET/CT
Description
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.
Time Frame
Baseline, Week 12
Title
Change Between Baseline and Week 12 in in the Extrathoracic Region as Measured by SUVmax[F-18]FDG-PET/CT
Description
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.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Other Parameters of Pulmonary Function Testing (FEV 1, 3, 6 Seconds and Predicted)
Description
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
Time Frame
Baseline, week 24
Title
Change From Baseline in High Resolution Computed Tomography (HRCT) Scoring
Description
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).
Time Frame
Baseline, Week 24
Title
Change From Baseline Distance Walked as Assessed by the 6-minute Walk Test
Description
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
Time Frame
Baseline, Week 12, and Week 24
Title
Change From Baseline of Additional [F-18]FDG-PET Outcomes
Description
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
Time Frame
Baseline, Week 12
Title
Change From Baseline in Other Parameters of Pulmonary Function Testing : Diffusion Capacity of Lung for CO
Description
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.
Time Frame
Baseline, week 24
Title
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)
Description
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
Time Frame
Baseline, week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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: 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.
Facility Information:
Facility Name
Novartis Investigative Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-0006
Country
United States
Facility Name
Novartis Investigative Site
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Novartis Investigative Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt
ZIP/Postal Code
60596
Country
Germany
Facility Name
Novartis Investigative Site
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Novartis Investigative Site
City
Nieuwegein
ZIP/Postal Code
3435 CM
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Rotterdam
ZIP/Postal Code
3015 CE
Country
Netherlands

12. IPD Sharing Statement

Links:
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=499
Description
A Plain Language Trial Summary is available on novartisclinicaltrials.com

Learn more about this trial

Study of Efficacy, Safety and Tolerability of ACZ885 (Canakinumab) in Patients With Pulmonary Sarcoidosis

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