known as granulomas that can affect how lungs work and breathing. sarcoidosis
Conditions
Interventions
Geen onderzoeksmedicatie
Sponsors
Celgene Corporation
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Subject are male or female * 18 and * 65 years of age, inclusive, at the time of signing the informed consent form (ICF)., 2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted., 3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements., 4. Subject has not received glucocorticoid as initial sarcoidosis therapy (* 20 mg/day prednisone or prednisolone) or other sarcoidosis therapy for at least 3 months or 5 PK half-lives, whichever is longer, prior to enrollment., 5. Subjects have a diagnosis of pulmonary sarcoidosis:, a. According to the ATS/ERS/WASOG (Appendix J) statement, supported by clinical presentation and biopsy-proven noncaseating granulomatous inflammation with no alternative cause of the granulomas;, b. With radiographic stage II or III disease;, c. With dyspnea (MRC grade * 1);, d. With an FVC as follows - * 45% and * 80% of predicted normal value at screening (for at least 10 subjects) - * 45% and * 90% of predicted normal value at screening (for no more than 14 subjects);, e. With or without concurrent extra-pulmonary sarcoidosis;, f. Without clinically significant neurosarcoidosis or cardiac sarcoidosis;, g. Without history of resistance or refractoriness to glucocorticoid induction therapy., 6. Subject is in good health (except for sarcoidosis) as determined by a physical examination at screening., a. Stable and mild syndromes associated with normal ageing, that are not expected to affect safe participation or data interpretation are allowed. Examples include, but are not limited to, systemic hypertension, hypothyroidism, prostatic hypertrophy, etc., 7. Contraception Requirements: Must comply with the following acceptable forms of contraception. All FCBP1 must use one of the approved contraceptive options as described below while participating in the study and for at least 28 days after the last study visit., At the time of study entry, and at any time during the study when a FCBP*s contraceptive measures or ability to become pregnant changes, the Investigator will educate the subject regarding contraception options and the correct and consistent use of effective contraceptive methods in order to successfully prevent pregnancy. All FCBP must have a negative pregnancy test at screening, Baseline (Day 1/Visit 1), Visit 3 and Visit 5. All FCBP subjects who engage in activity in which conception is possible must use one of the approved contraceptive options described below:, Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner*s vasectomy; OR, Option 2: Male or female condom (latex condom or non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]); PLUS one additional barrier(c) contraceptive sponge with spermicide. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex or non-latex condoms NOT made out of natural [animal] membrane [for example, polyurethane]) while on the study and for at least 28 days after the last study visit., 8. Subject has body mass index (BMI) * 17 an
Exclusion criteria
Exclusion criteria: 1. Subject has any significant medical condition, laboratory abnormality, neurological disease or psychiatric illness that would prevent the subject from safely completing the study. Prior evidence of neurological disease must be documented., 2. Subject has any condition that confounds the ability to interpret data from the study., 3. Subject is a pregnant or a nursing female., 4. Subject has received another interventional investigational drug for sarcoidosis within the 3 months prior to screening or 5 PK half-lives, whichever is longer*., 5. Subject has clinically significant lung disease, other than sarcoidosis, such as asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD) or lung cancer., a. Subject has a history of significant (greater than a wedge) lung resection., 6. Subject is receiving therapy for sarcoidosis associated pulmonary hypertension, or has an indication for such therapy., 7. Subject has uncontrolled diabetes and/or other contraindications to glucocorticoid therapy., 8. Subject has a history of listeriosis, coccidioidomycosis, histoplasmosis, blastomycosis, treated or untreated tuberculosis or exposure to individuals with tuberculosis., 9. Subject is an active smoker or has > 10 pack-year smoking history. Previous smokers must have discontinued smoking for at least 1 year., 10. Subject is unable to perform any study-related procedure or maneuver., 11. Subject has had any biologic anti-tumor necrosis factor (anti-TNF) therapy within the previous year., 12. Subject has active infection requiring treatment within 30 days prior to screening*., 13. Subject has a positive QuantiFERON-TB Gold tuberculosis test., a. In case of an indeterminate result, the test may be repeated once. The repeat result must be negative to permit entry into the study., 14. Subject has active fungal infection (other than candidiasis of the urinary tract*) or active infection with hepatitis B or hepatitis C or a history of either HCV infection or chronic HBV infection., 15. Subject has a history of congenital and/or acquired immunodeficiencies (eg, common variable immunodeficiency, HIV, etc.)., 16. Subject has aspartate transaminase (AST), alanine aminotransferase (ALT) or total bilirubin > 2 x the upper limit of normal at screening (unless the increase is considered to be due to sarcoidosis by the Investigator and/or Sponsor*s medical monitor)., 17. Subject has a serum creatinine level > 1.8 mg/dL (> 159.12 *mol/L), 18. Subject has clinically significant organic heart disease (eg, congestive heart failure), myocardial infarction requiring initiation or change in medical treatment within six months prior to screening., 19. Subject has QTcF of > 450 milliseconds or findings on electrocardiogram (ECG) at screening (eg, an arrhythmia, heart block, etc.) that suggest either significant cardiac sarcoidosis or significant risk of cardiac adverse event over the duration of this study., 20. Subject has a history of malignancy within 5 years (except basal cell carcinoma of the skin that is surgically cured, remote history of cancer now considered cured or positive pap smear with subsequent negative follow-up)., 21. Subject is expecting to have elective surgery in the time interval between screening and 10 weeks after the last study visit i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint: HRCT Description: * HRCT-based metrics of Sarcoid activity and progression, lobar volumes at TLC and FRC, and airway wall volumes | — |
Secondary
| Measure | Time frame |
|---|---|
| Exploratory Endpoint: HRCT Description: * Lung volumes at FRC and TLC * (specific) CFD- based Airway resistance at FRC and TLC * (specific) Airway volume down to generation 8-10 at TLC * (specific) Airway volume down to generation 4-5 at FRC * Air Trapping at FRC * Internal airflow distribution based on lobar expansion * Emphysema score on lobar level Exploratory Endpoints: Pulmonary Function Tests (PFTs) Description: * forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), diffusing capacity of lung for carbon monoxide (DLCO), total lung capacity (TLC) and functional residual capacity (FRC), six-minute walk test (6MWT) For other Exploratory Endpoints see protocol under Table 2: Study Endpoints | — |
Countries
Netherlands
Outcome results
None listed