Study of Efficacy, Safety and Tolerability of CMK389 in Patients With Chronic Pulmonary Sarcoidosis
Primary Purpose
Pulmonary Sarcoidosis
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
CMK389
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Sarcoidosis focused on measuring chronic pulmonary sarcoidosis
Eligibility Criteria
Inclusion Criteria:
- Subjects must have a body mass index (BMI) at screening within the range of 18 - 46 kg/m2. BMI = Body weight (kg) / [Height (m)]2
- Biopsy proven pulmonary sarcoidosis diagnosed > 1 year prior to screening
- Scadding stage II, III or IV as determined by the most recent chest x-ray obtained within 12 months prior to screening or at screening (confirmed by the Investigator)
- HRCT extent of fibrosis <20% (confirmed by the central imaging reader) at screening
- Treatment with 5-15 mg/day prednisone (or prednisone oral equivalents) for ≥ 6 months prior to screening.
- Co-medication with methotrexate or azathioprine for ≥ 6 months prior to screening (Note: hydroxychloroquine is allowed as background therapy but not required)
- Able to perform reliable, reproducible pulmonary function test maneuvers per American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines
Exclusion Criteria:
- Diagnosis of significant pulmonary hypertension (WHO group 5) requiring pharmacological treatment
- Active cardiac sarcoidosis requiring treatment. Inactive cardiac sarcoidosis or stable cardiac sarcoidosis not requiring treatment are permissible.
- A known diagnosis of neurosarcoidosis
- Forced vital capacity (FVC) <50% of predicted at screening (central read)
- Modified British Medical Research Council (mMRC) dyspnea scale ≥ 3 at screening
- Concomitant treatment with leflunomide, cyclophosphamide, mycophenolate, infliximab, etanercept, adalimumab, golimumab, ustekinumab, roflumilast, pentoxifylline, and abatacept within 12 weeks of screening
- Prior treatment with rituximab, canakinumab, anakinra, and tocilizumab
- Current use of any inhaled substance, including but not limited to tobacco, marijuana products and use of electronic cigarette or vaping device, and excluding inhalers or nebulizers prescribed for pulmonary sarcoidosis
- Any conditions or significant medical problems which in the opinion of the investigator and in consultation with the sponsor, immunocompromises the patient and/or places the patient at unacceptable risk for immunomodulatory therapy
- Contraindication to FDG-PET scan investigations such as severe claustrophobia or uncontrolled diabetes
- History or current diagnosis of ECG abnormalities not due to Cardiac Sarcoidosis and indicating significant risk of safety for patients participating in the study
- A diagnosis of Lofgren's syndrome
- A history of pancreatitis
Other protocol-defined inclusion/exclusion criteria may apply
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
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- 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
CMK389
Placebo
Arm Description
CMK389
Placebo
Outcomes
Primary Outcome Measures
Forced Vital Capacity
Change in forced vital capacity, % of predicted, between CMK389 and placebo.
Secondary Outcome Measures
Composite index of pulmonary physiology and exercise capacity
Relative reduction in forced volume capacity ≥ 10% or relative reduction in forced expiratory volume in one second ≥ 10% or relative reduction of diffusion capacity ≥ 15% or relative reduction of 6-minute walk distance ≥ 50 meters.
[18F]-fluorodeoxyglucose positron emission tomography/computed tomography
Change in imaging maximum standardized uptake value and mean standardized uptake value.
Pulmonary physiology
Change in forced expiratory volume in one second and diffusion capacity for carbon monoxide.
Steroid use (mg days)
Difference in steroid usage for each arm of the study.
Exercise capacity
Change in 6-minute walk distance.
Pharmacokinetics of CMK389 maximum concentration (Cmax)
The observed maximum plasma concentration (Cmax/end of infusion) [mass / volume].
Pharmacokinetics of CMK389 trough concentration (Ctrough)
The lowest concentration of drug (Ctrough) reached before the next dose is administered.
Full Information
NCT ID
NCT04064242
First Posted
August 20, 2019
Last Updated
October 20, 2023
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT04064242
Brief Title
Study of Efficacy, Safety and Tolerability of CMK389 in Patients With Chronic Pulmonary Sarcoidosis
Official Title
A Subject and Investigator Blinded, Randomized, Placebo-controlled, Repeat-dose, Multicenter Study to Investigate Efficacy, Safety, and Tolerability of CMK389 in Patients With Chronic Pulmonary Sarcoidosis
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 23, 2020 (Actual)
Primary Completion Date
September 19, 2023 (Actual)
Study Completion Date
January 19, 2024 (Anticipated)
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 proof of concept study is to determine whether CMK389 displays the safety and efficacy profile to support further development in chronic pulmonary sarcoidosis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Sarcoidosis
Keywords
chronic pulmonary sarcoidosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Participants will be assigned to one of two treatment arms, either CMK389 or placebo.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
62 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CMK389
Arm Type
Experimental
Arm Description
CMK389
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
CMK389
Intervention Description
single i.v. dose every 4 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
single i.v. dose every 4 weeks
Primary Outcome Measure Information:
Title
Forced Vital Capacity
Description
Change in forced vital capacity, % of predicted, between CMK389 and placebo.
Time Frame
Baseline to Week 16
Secondary Outcome Measure Information:
Title
Composite index of pulmonary physiology and exercise capacity
Description
Relative reduction in forced volume capacity ≥ 10% or relative reduction in forced expiratory volume in one second ≥ 10% or relative reduction of diffusion capacity ≥ 15% or relative reduction of 6-minute walk distance ≥ 50 meters.
Time Frame
Baseline to Week 16
Title
[18F]-fluorodeoxyglucose positron emission tomography/computed tomography
Description
Change in imaging maximum standardized uptake value and mean standardized uptake value.
Time Frame
Baseline to Week 16
Title
Pulmonary physiology
Description
Change in forced expiratory volume in one second and diffusion capacity for carbon monoxide.
Time Frame
Baseline to Week 16
Title
Steroid use (mg days)
Description
Difference in steroid usage for each arm of the study.
Time Frame
Baseline to Week 16
Title
Exercise capacity
Description
Change in 6-minute walk distance.
Time Frame
Baseline to Week 16
Title
Pharmacokinetics of CMK389 maximum concentration (Cmax)
Description
The observed maximum plasma concentration (Cmax/end of infusion) [mass / volume].
Time Frame
Day 1 through Week 28
Title
Pharmacokinetics of CMK389 trough concentration (Ctrough)
Description
The lowest concentration of drug (Ctrough) reached before the next dose is administered.
Time Frame
Day 1 through Week 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must have a body mass index (BMI) at screening within the range of 18 - 46 kg/m2. BMI = Body weight (kg) / [Height (m)]2
Biopsy proven pulmonary sarcoidosis diagnosed > 1 year prior to screening
Scadding stage II, III or IV as determined by the most recent chest x-ray obtained within 12 months prior to screening or at screening (confirmed by the Investigator)
HRCT extent of fibrosis <20% (confirmed by the central imaging reader) at screening
Treatment with 5-15 mg/day prednisone (or prednisone oral equivalents) for ≥ 6 months prior to screening.
Co-medication with methotrexate or azathioprine for ≥ 6 months prior to screening (Note: hydroxychloroquine is allowed as background therapy but not required)
Able to perform reliable, reproducible pulmonary function test maneuvers per American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines
Exclusion Criteria:
Diagnosis of significant pulmonary hypertension (WHO group 5) requiring pharmacological treatment
Active cardiac sarcoidosis requiring treatment. Inactive cardiac sarcoidosis or stable cardiac sarcoidosis not requiring treatment are permissible.
A known diagnosis of neurosarcoidosis
Forced vital capacity (FVC) <50% of predicted at screening (central read)
Modified British Medical Research Council (mMRC) dyspnea scale ≥ 3 at screening
Concomitant treatment with leflunomide, cyclophosphamide, mycophenolate, infliximab, etanercept, adalimumab, golimumab, ustekinumab, roflumilast, pentoxifylline, and abatacept within 12 weeks of screening
Prior treatment with rituximab, canakinumab, anakinra, and tocilizumab
Current use of any inhaled substance, including but not limited to tobacco, marijuana products and use of electronic cigarette or vaping device, and excluding inhalers or nebulizers prescribed for pulmonary sarcoidosis
Any conditions or significant medical problems which in the opinion of the investigator and in consultation with the sponsor, immunocompromises the patient and/or places the patient at unacceptable risk for immunomodulatory therapy
Contraindication to FDG-PET scan investigations such as severe claustrophobia or uncontrolled diabetes
History or current diagnosis of ECG abnormalities not due to Cardiac Sarcoidosis and indicating significant risk of safety for patients participating in the study
A diagnosis of Lofgren's syndrome
A history of pancreatitis
Other protocol-defined inclusion/exclusion criteria may apply
Facility Information:
Facility Name
Novartis Investigative Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-3300
Country
United States
Facility Name
Novartis Investigative Site
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Novartis Investigative Site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160-7330
Country
United States
Facility Name
Novartis Investigative Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Novartis Investigative Site
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Novartis Investigative Site
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27858
Country
United States
Facility Name
Novartis Investigative Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Novartis Investigative Site
City
Brno Bohunice
ZIP/Postal Code
625 00
Country
Czechia
Facility Name
Novartis Investigative Site
City
Olomouc
ZIP/Postal Code
779 00
Country
Czechia
Facility Name
Novartis Investigative Site
City
Aarhus N
ZIP/Postal Code
8200
Country
Denmark
Facility Name
Novartis Investigative Site
City
Hellerup
ZIP/Postal Code
2900
Country
Denmark
Facility Name
Novartis Investigative Site
City
Odense C
ZIP/Postal Code
DK 5000
Country
Denmark
Facility Name
Novartis Investigative Site
City
Heidelberg
State/Province
Baden-Württemberg
ZIP/Postal Code
69126
Country
Germany
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
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Novartis Investigative Site
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Novartis Investigative Site
City
Bialystok
ZIP/Postal Code
15-044
Country
Poland
Facility Name
Novartis Investigative Site
City
Lodz
ZIP/Postal Code
90 153
Country
Poland
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
01-138
Country
Poland
Facility Name
Novartis Investigative Site
City
Edinburgh
ZIP/Postal Code
EH1 1BE
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
SW3 6PH
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Learn more about this trial
Study of Efficacy, Safety and Tolerability of CMK389 in Patients With Chronic Pulmonary Sarcoidosis
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