Active pulmonary sarcoidosis Respiratory
Conditions
Interventions
Subjects will be randomized in a 1:1 ratio under double-blind conditions according to the IRT electronic system to receive either 25 mg film-coated oral OATD-01 tablets or oral placebo tablets. Random
the study drug will be also taken at the onsite visits W4 and W8 and EOT visit (if coincides with the last day of treatment).
Treatment compliance will be source-documented in a subject’s diary and
Sponsors
Molecure S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects with active symptomatic pulmonary sarcoidosis, (definite diagnosis of active pulmonary sarcoidosis per ATS guidelines) 2. Treatment-naïve or previously treated (no recruitment cap) 3. Parenchymal pulmonary involvement on [18F]FDG PET/CT
Exclusion criteria
Exclusion criteria: 1. Requirement for immediate start of standard of care therapy for pulmonary sarcoidosis 2. Cardiac or neuro- sarcoidosis 3. History of/active Löfgren syndrome 4. Clinically significant lung disease other than sarcoidosis (e.g. tuberculosis, asthma, Chronic Obstructive Pulmonary Disease, interstitial lung disease, lung cancer) or any current inflammatory or immunological systemic disease other than sarcoidosis 5. Potentially effective systemic or inhaled pharmacological (including investigational) therapy for sarcoidosis (whether pulmonary or other disease), with the exception of any of the following: a. corticosteroids received not later than 3 months prior to enrolment b. immunosuppressants or anti-TNF agents (or other anti-inflammatory/anti-fibrotic treatment) received not later than 4 months prior to enrolment 6. Systemic treatment indication being an extrapulmonary location of sarcoidosis (e.g., neurological) 7. Heart conditions: QTcF interval prolongation, cardiac arrhythmia (other than non-sustained supraventricular arrhythmia), heart failure (New York Heart Association class III or IV) and/or known myocardial hypertrophy or Left Ventricle Ejection Fraction 37°C and any metabolic disease affecting the energy metabolism of muscles) as described in the separately provided PET protocol 11. Known positivity for Human Immunodeficiency Virus (HIV 1/2 antibodies), hepatitis B virus (HBV), or hepatitis C virus (HCV), or detected at screening 12. Severe, uncontrolled systemic disease (e.g., cardiovascular, pulmonary, thyroid, renal or metabolic disease) at Screening, or other condition, which in the opinion of the investigator, would compromise the safety of the subject or the subject’s ability to participate in the study 13. Current smoker of >5 cigarettes or e-cigarettes per day or user of nicotine-releasing alternatives (patches, chewing gums etc) 14. Prohibited medications: Current treatment with drug with QT prolongation effect, thiazide diuretics, strong CYP3A4 inhibitors and/or inducers, P-glycoprotein and/or BCRP strong inhibitors, drugs that are sensitive substrates of OCT1, MATE1, MATE2K, OAT3 with a narrow therapeutic index
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response to treatment from baseline to End-of-Treatment (EOT) classed as Complete response, Partial response, Stable disease and Progressive disease based on Standard Uptake Volume (SUV) changes in the uptake for {18F]FDG-PET/CT above the background (pulmonary parenchyma/ascending aorta) in pulmonary target lesions and any new lesions | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Granulomatous inflammation evaluated by [18F]FDG PET/CT imaging, quantified as the percent change of maximum, mean, peak SUV (SUVmax, SUVmean, SUVpeak), and volume of the lesions in pulmonary parenchyma, mediastinal/hilar nodes, and extrathoracic locations at Screening and EoT 2. Number of patients escaping to corticosteroids. Discontinuing the treatment with IMP and escaping to standard-of-care treatment will be captured promptly at EOT for efficacy evaluation. Subjects with study treatment discontinued and escape therapy prescribed will be followed up for safety up until W12 visit. 3. Absolute change in Forced Vital Capacity (FVC, % predicted) and Forced Expiratory Volume in the first second (FEV1) at Screening, W0, W4, W8 and EoT 4. Quality of life measured by the Kings Sarcoidosis Questionnaire General and Lung (KSQ GENERAL and LUNG) scores at W0, EoT and W12 5. Occurrence of Treatment-emergent Adverse Events (TEAEs), SAEs, Adverse Events of Special Interest (AESIs), TEAEs leading to discontinuation and TEAEs leading to death, recorded from the time of signature of informed consent until 30 days after the last of OATD-01/Placebo. 6. Occurrence of clinically significant laboratory (hematology and biochemistry) parameter abnormalities 7. Mean change in vital signs (systolic and diastolic blood pressure, heart rate, respiratory rate) at Screening, W0, W2, W4, W8, EoT, W12 and FUP 8. Occurrence of any clinically significant abnormalities in 12-lead electrocardiography (ECG) or 24-h ECG at Screening, W0, W2, W4, W8, EoT, W12 and FUP 9. Change from baseline and in between visits in cardiac safety parameters evaluated by 12-lead ECG [Heart Rate (HR) , PR QTcF and QRS] at Screening, W0, W2, W4, W8 and EoT 10. Occurrence of: 10.1. QTcF >450 ms (male), >470 ms (female) and >500 ms (any sex) 10.2. Change from baseline in QTcF >30 ms and >60 ms 11. Heart rhythm abnormalities including supraventricular arrhythmias, ventricular arrhythmias, and non-sustained ventricular ta | — |
Countries
Denmark, England, France, Germany, Greece, Netherlands, Norway, Poland, Scotland, United Kingdom, United States of America
Contacts
Public ContactNikhil Hirani
Outcome results
None listed