Efficacy and Safety Study of OATD-01 in Patients With Active Pulmonary Sarcoidosis

Phase 2RecruitingNCT06205121

Molecure S.A.96 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Pulmonary Sarcoidosis

Interventions

OATD-01DRUG

OATD-01 is an oral inhibitor of chitinase-1 (CHIT1)

PlaceboDRUG

Matching placebo tablets

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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: 1. corticosteroids received not later than 3 months prior to enrolment 2. 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 * Lab abnormalities: Abnormal bilirubin, transaminases, alkaline phosphatase (ALP), Creatinine clearance (CrCL) Hypokalemia hypocalcemia (\<2.1 mmol/L), marked fasting hyperglycemia at screening * Uncontrolled diabetes at Screening with plasma glucose exceeding 8.3 mmol/L, or other contraindication to \[18F\]FDG administration and/or PET procedure (including body temperature \>37°C and any metabolic disease affecting the energy metabolism of muscles) as described in the PET protocol * Known positivity for Human Immunodeficiency Virus (HIV 1/2 antibodies), hepatitis B virus (HBV), or hepatitis C virus (HCV), or detected at screening * 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 * Current smoker of \>5 cigarettes or e-cigarettes per day or user of nicotine-releasing alternatives (patches, chewing gums etc) * 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, pirfenidone and nintedanib.

Locations (28)

Outcomes

Primary Outcomes

Response to treatment

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.

Time frame: After 12 weeks of treatment, i.e. from baseline (randomization) visit to End-of-Treatment (EOT) visit.

Secondary Outcomes

Total granulomatous inflammation evaluation

Evaluation 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.

Time frame: After 12 weeks of treatment, i.e. from baseline (randomization) visit to EOT visit.

Pulmonary function Forced Vital Capacity (FVC)

Absolute change in FVC (% predicted).

Time frame: At Screening visit and over 12 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)

Absolute change in FEV1 (% predicted).

Time frame: At Screening visit and over 12 weeks of treatment - at baseline (randomization) visit, at week 4 of treatment, week 8 and week 12 (EOT).

Quality of life assessment

Change in the quality of life measured by the Kings Sarcoidosis Questionnaire General and Lung (KSQ GENERAL and LUNG) scores. Range of each module 0-100, 100= best health status.

Time frame: Assessed at baseline (randomization) visit and after 12 weeks of treatment (EOT visit) or study participation (week 12 visit).

Central Contacts

Theodoros Charitos, MD

CONTACT

+48789125928 t.charitos@molecure.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Molecure Investigative Site

Birmingham, Alabama, United States

WITHDRAWN

Molecure Investigative Site

Kansas City, Kansas, United States

WITHDRAWN

Molecure Investigative Site

Baltimore, Maryland, United States

RECRUITING

Molecure Investigative Site

Rochester, Minnesota, United States

WITHDRAWN

Molecure Investigative Site

Cleveland, Ohio, United States

RECRUITING

Molecure Investigative Site

Philadelphia, Pennsylvania, United States

RECRUITING

Molecure Investigative Site

Charleston, South Carolina, United States

RECRUITING

Molecure Investigative Site

Vejle, Denmark

WITHDRAWN

Molecure Investigative Site

Bobigny, France

WITHDRAWN

Molecure Investigative Site

Montpellier, France

RECRUITING

...and 18 more locations

Fatigue Assessment Scale (FAS)

Change in FAS total score. Range: 10 (no fatigue) - 50 (extreme fatigue).

Time frame: Assessed at baseline (randomization) visit and after 12 weeks of treatment (EOT visit) or study participation (week 12 visit).

Adverse events

Occurrence of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events, Adverse Events of Special Interest (AESIs), TEAEs leading to discontinuation and TEAEs leading to death.

Time frame: Recorded from the time of signature of informed consent and until 30 days after the last dose of OATD-01/Placebo.

Laboratory tests

Occurrence of clinically significant laboratory (hematology and biochemistry) parameter abnormalities (number of subjects with clinically significant abnormal laboratory values).

Time frame: 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).

Vital signs - Systolic Blood Pressure

Mean change in Systolic Blood Pressure.

Time frame: 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 - Diastolic Blood Pressure

Mean change in Diastolic Blood Pressure.

Time frame: 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.

Vital signs

Mean change in Heart Rate.

Time frame: 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.

Vital signs - Respiratory Rate

Mean change in Respiratory Rate

Time frame: 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

Occurrence of any clinically significant abnormalities (number of patients with any clinically significant Heart rhythm, PR Interval, QTcF interval or QRS width interval abnormalities) in 12-lead electrocardiography (ECG) or 24-h ECG.

Time frame: 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.

Electrocardiography - specific parameters

Occurrence of: a) QTcF \>450 ms (male), \>470 ms (female) and \>500 ms (any sex) b) Change from baseline in QTcF \>30 ms and \>60 ms c) Heart rhythm abnormalities including supraventricular arrhythmias, ventricular arrhythmias, and non-sustained ventricular tachycardias.

Time frame: 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.

Male fertility

Occurrence of a clinically significant abnormality of sperm parameters and/ or free testosterone concentration in males (optional testing)

Time frame: Measured at baseline (randomization) visit and at week 8 or week 12 (EOT) of treatment.

Neurological status

Occurrence of TEAEs of sensation abnormalities or ataxia.

Time frame: 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

Thyroid and renal function

Proportion of subjects with clinically significant thyroid parameters (Thyroid Stimulating Hormone \[TSH\], Free Triiodothyronine \[FT3\], and Free Thyroxine \[FT4\] and renal function parameters \[blood urea nitrogen (BUN)/total urea, creatinine, creatinine clearance (CrCL)\].

Time frame: Clinically significant abnormalities detected during 12 weeks of treatment - at baseline (randomization) visit, at week 4 of treatment, week 8 and week 12 (EOT).

Pharmacokinetics assessment

Mean plasma OATD-01 concentrations.

Time frame: Measured during 2 weeks of treatment - at baseline (randomization) visit, at week 4 of treatment, week 8 and week 12 (EOT).