Besnier-Boeck-Schaumann disease / inflamatory disease
Conditions
Interventions
Screening Assessments:
- Physical examination / Vital signs
- ECG
- CT and FDG-PET scan
- Breathing tests
- Blood and urine collection
Treatment period
- Physical examination / Vital signs
- ECG
- CT
Sponsors
Kinevant Sciences Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male or female subjects age >=18 years. 2. Able and willing to provide written informed consent, which includes compliance with study requirements and restrictions listed in the consent form. 3. >=6-month history of documented sarcoidosis including histological confirmation in the subject*s medical records. 4. Have HRCT and [18F]-FDG PET/CT scans at Screening consistent with active pulmonary sarcoidosis of the lung parenchyma by central read. 5. ppFVC >=50% to =50% at Screening. 6. If receiving prednisone (or equivalent), dose must have been =3 months prior to Screening and subject must agree to cessation of their IST therapy at randomization. 8. Symptomatic as indicated by modified Medical Research Council Dyspnea scale >1 (i.e., Grade 2 or more) in the prior 6 months. 9. Female subjects must agree to use an approved highly effective birth control (BC) method (40 years) a documented serum FSH level must be >=30 mIU/mL; • Woman of childbearing potential (WCBP) who is already using an established method of highly effective contraception or agrees to use one of the allowed BC methods, for at least 28 days prior to randomization and throughout the study, and for 8 weeks (56 days) following the last dose of study drug. 10. Male subjects must agree to, and attest that, female partners of childbearing potential are using one of the allowed highly effective methods of contraception as described above and for consistent duration. 11. Body Mass Index (BMI)
Exclusion criteria
Exclusion criteria: 1. Hospitalized for any respiratory illness =20% fibrosis as indicated on HRCT-scan assessed by central read prior to randomization. 3. Estimated glomerular filtration rate (eGFR) 2 × upper limit of normal range (ULN). 5. Platelet count 3.5 mmol/L (14 mg/dL). 9. Positive for anti-GM-CSF autoantibody, or history of pulmonary alveolar proteinosis (PAP). 10. Use of any biologic immunomodulator agent (approved or investigational) within the 6 months prior to Screening. Allergens for hypersensitivity desensitization or vaccines are not excluded per this criterion. Treatment with immunoglobulin within 6 months prior to Screening. Treatment with any investigational immunomodulator (e.g., Neuropilin 2 (NRP2) modulator) within 6 months prior to Screening. 11. Treatment with any Janus kinase (JAK) inhibitor within 3 months prior to Screening. 12. Participation in another interventional clinical trial within 6 months prior to Screening. 13. History of left ventricular ejection fraction (LVEF) 480 msec on the 12-lead ECG at Screening; if QTcF exceeds 480 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF measures should be used to determine eligibility. 15. Pulmonary hypertension requiring therapy. 16. Systolic blood pressure (SBP) 180 mm Hg; Diastolic blood pressure (DBP) 110 mm Hg at screening. 17. Has documented laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other approved clinical testing =12 months prior to randomization is allowed. 25. Prior use within 12 months of Screening of, or inability to refrain from throughout the study period and 8 weeks (56 days) after last dose of study drug, smoking or using any form of inhaled tobacco, inhaled nicotine (including vaping) or inhaled cannabis preparations. 26. A diagnosis of, or presentation consistent with, Lofgren*s syn
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Mean change from baseline in percent predicted forced vital capacity (ppFVC) at 26 weeks; | — |
Secondary
| Measure | Time frame |
|---|---|
| Primary Endpoint: • Mean change from baseline in percent predicted forced vital capacity (ppFVC) at 26 weeks; Key Secondary Endpoint: • Proportion of subjects successfully achieving OCS taper without rescue; Other Secondary Endpoints: Other secondary endpoints of the study include the following: • Safety and tolerability, including assessment of physical examinations (PEs), vital signs, electrocardiograms (ECGs), clinical laboratory measurements, serum surfactant protein D (SP-D) measurements, local injection site tolerability, concomitant medications, and adverse events (AEs); • Pulmonary function tests (PFTs): • Mean change from baseline in FVC (mL); • Percent of subjects in each category: > +10%, +10% to -10%, =10% from baseline in ppFVC or DLCO, or mKSQ Lung Score improvement of >=4 points, or improvement in Fatigue FAS of >=4 points, without clinically relevant decline in these parameters or need for rescue with OCS and/or ISTs; • Time-to-clinical worsening (TTCW) is defined by the time to the first occurrence of the following: Decline of >=10% from baseline in ppFVC or diffusing capacity of lung for carbon monoxide (DLCO), or mKSQ Lung score decline of >=4 points, or decline in Fatigue FAS of >=4 points, or need for rescue with OCS and/or ISTs. • Mean change from baseline in sarcoid associated skin lesions (when present at baseline) and/or development of new skin lesions as assessed by the Sarcoidosis Activity and Severity Index (SASI); • Mean change from baseline in extrapulmonary Physician Organ Severity Tool (ePOST); • Proportion of subjects requiring use of rescue therapy; • PPK and E-R relationship assessments for efficacy and safety, where data permit: • area under the concentration-time curve (AUC), maximum observed concentration (Cmax), minimum plasma concentration (Cmin), average plasma concentration over the dosing interval (Cavg), and time of Cmax (Tmax); • Exposure-change from baseline in ppFVC and change from base | — |
Countries
Netherlands
Outcome results
None listed