A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Assess the Efficacy and Safety of a 12-week Administration of OATD-01, an Oral Inhibitor of Chitinase-1 (CHIT1), for the Treatment of Active Pulmonary Sarcoidosis (the KITE Study)
Overview
- Phase
- Phase 2
- Intervention
- OATD-01
- Conditions
- Pulmonary Sarcoidosis
- Sponsor
- Molecure S.A.
- Enrollment
- 96
- Locations
- 1
- Primary Endpoint
- Response to treatment
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This is a Phase 2, randomized, double-blind, placebo-controlled, adaptive, multicenter study to evaluate the efficacy, safety, tolerability, Pharmacodynamics (PD), and Pharmacokinetics (PK) of OATD-01 in the treatment of subjects with active pulmonary sarcoidosis.
Detailed Description
Adult subjects (≥ 18 years of age) diagnosed with symptomatic pulmonary sarcoidosis and active granulomatous process captured by \[18F\]Fluorodeoxyglucose Positron emission tomography/computed tomography (\[18F\]FDG PET/CT) imaging, treatment-naïve or previously treated but currently untreated, will be enrolled in the study. The diagnosis of pulmonary sarcoidosis will be based on the diagnostic criteria for pulmonary sarcoidosis recommended by the American Thoracic Society (ATS, 2020). Subjects will be randomized in a 1:1 ratio to receive either OATD-01 or placebo for 12 weeks. A stratification of the study population based on previous treatment status for sarcoidosis (previously treated/treatment-naïve) will be applied for statistical analysis without limitation for the ratio between the subject groups. Double-blind conditions will be kept for the whole treatment duration.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female subjects with active symptomatic pulmonary sarcoidosis, (definite diagnosis of active pulmonary sarcoidosis per ATS guidelines)
- •Treatment-naïve or previously treated (no recruitment cap)
- •Parenchymal pulmonary involvement on \[18F\]FDG PET/CT
Exclusion Criteria
- •Requirement for immediate start of standard of care therapy for pulmonary sarcoidosis
- •Active cardiac or neuro- sarcoidosis
- •History of/active Löfgren syndrome
- •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
- •Potentially effective systemic or inhaled pharmacological (including investigational) therapy for sarcoidosis (whether pulmonary or other disease), with the exception of any of the following:
- •corticosteroids received not later than 3 months prior to enrolment
- •immunosuppressants or anti-Tumor Necrosis Factor (TNF) agents (or other anti-inflammatory/anti-fibrotic treatment) received not later than 4 months prior to enrolment
- •Systemic treatment indication being an extrapulmonary location of sarcoidosis (e.g., neurological)
- •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 \<50% in the cardiac MRI
- •Known neurosarcoidosis or small fiber neuropathy or medical conditions causing primary ataxia
Arms & Interventions
Active Arm
Subjects will receive OATD-01 as 25mg film-coated tablets for oral administration once daily for 12 weeks
Intervention: OATD-01
Placebo Arm
Subjects will receive placebo as film-coated tablets for oral administration once daily for 12 weeks
Intervention: Placebo
Outcomes
Primary Outcomes
Response to treatment
Time Frame: After 12 weeks of treatment, i.e. from baseline (randomization) visit to End-of-Treatment (EOT) visit.
Response 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 Outcomes
- Pulmonary function Forced Vital Capacity (FVC)(At Screening visit and over 12 weeks of treatment - at baseline (randomization) visit, at week 4 of treatment, week 8 and week 12 (EOT).)
- Vital signs - Diastolic Blood Pressure(Measured at screening and over 12 weeks of treatment or study participation - at baseline (randomization) visit, at week 2 of treatment, week 4, week 8, week 12 (EOT) and any FUP visits.)
- Total granulomatous inflammation evaluation(After 12 weeks of treatment, i.e. from baseline (randomization) visit to EOT visit.)
- Fatigue Assessment Scale (FAS)(Assessed at baseline (randomization) visit and after 12 weeks of treatment (EOT visit) or study participation (week 12 visit).)
- Adverse events(Recorded from the time of signature of informed consent and until 30 days after the last dose of OATD-01/Placebo.)
- Vital signs - Systolic Blood Pressure(Measured at screening and over 12 weeks of treatment or study participation - at baseline (randomization) visit, at week 2 of treatment, week 4, week 8, week 12 (EOT) and any Follow-up (UP) visits)
- Vital signs - Respiratory Rate(Measured at screening and over 12 weeks of treatment or study participation - at baseline (randomization) visit, at week 2 of treatment, week 4, week 8, week 12 (EOT) and any FUP visits)
- Electrocardiography - specific parameters(Measured at screening and over 12 weeks of treatment or study participation - at baseline (randomization) visit, at week 2 of treatment, week 4, week 8, week 12 (EOT) and any FUP visits.)
- Quality of life assessment(Assessed at baseline (randomization) visit and after 12 weeks of treatment (EOT visit) or study participation (week 12 visit).)
- Laboratory tests(Measured at screening and over 12 weeks of treatment or study participation - at baseline (randomization) visit, at week 2 of treatment, week 4, week 8 and week 12 (EOT).)
- Neurological status(TEAEs detected during 12 weeks of treatment or study participation - from baseline (randomization) visit and up to FUP visit 7-10 days after last dose)
- Pharmacokinetics assessment(Measured during 2 weeks of treatment - at baseline (randomization) visit, at week 4 of treatment, week 8 and week 12 (EOT).)
- Pulmonary function Forced Expiratory Volume in the first second (FEV1)(At Screening visit and over 12 weeks of treatment - at baseline (randomization) visit, at week 4 of treatment, week 8 and week 12 (EOT).)
- Vital signs(Measured at screening and over 12 weeks of treatment or study participation - at baseline (randomization) visit, at week 2 of treatment, week 4, week 8, week 12 (EOT) and any FUP visits.)
- Thyroid and renal function(Clinically significant abnormalities detected during 12 weeks of treatment - at baseline (randomization) visit, at week 4 of treatment, week 8 and week 12 (EOT).)
- Electrocardiography(12-lead-ECG measured at screening and over 12 weeks of treatment or study participation - at randomization visit, at week 2 of treatment, week 4, week 8, week 12 (EOT) and any FUP visits. 2-week 24-h-ECG recordings at weeks 0, 4 and 8 post randomization.)
- Male fertility(Measured at baseline (randomization) visit and at week 8 or week 12 (EOT) of treatment.)