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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Sarcoidosis
• Intervention / Treatment: Drug: Placebo; Drug: OATD-01

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.

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Theodoros Charitos, MD; Phone Number: +48789125928; Email: t.charitos@molecure.com

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • Not yet recruiting
    • Molecure Investigative Site
  • Edinburgh, United Kingdom, EH16 4SA
    • Recruiting
    • Molecure Investigative Site
  • London, United Kingdom, SE5 9RS
    • Not yet recruiting
    • Molecure Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Recruiting
      • Molecure Investigative Site
  • Kansas
    • Kansas City, Kansas, United States, 66062
      • Not yet recruiting
      • Molecure Investigative Site
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Not yet recruiting
      • Molecure Investigative Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Molecure Investigative Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Not yet recruiting
      • Molecure Investigative Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Recruiting
      • Molecure Investigative Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Not yet recruiting
      • Molecure Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Arm; Subjects will receive OATD-01 as 25mg film-coated tablets for oral administration once daily for 12 weeks	Drug: OATD-01; OATD-01 is an oral inhibitor of chitinase-1 (CHIT1)
Placebo Comparator: Placebo Arm; Subjects will receive placebo as film-coated tablets for oral administration once daily for 12 weeks	Drug: Placebo; Matching placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	After 12 weeks of treatment, i.e. from baseline (randomization) visit to End-of-Treatment (EOT) visit.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	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).	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.	Assessed at baseline (randomization) visit and after 12 weeks of treatment (EOT visit) or study participation (week 12 visit).
Fatigue Assessment Scale (FAS)	Change in FAS total score. Range: 10 (no fatigue) - 50 (extreme fatigue).	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.	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).	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.	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.	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.	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	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.	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.	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)	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.	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)].	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.	Measured during 2 weeks of treatment - at baseline (randomization) visit, at week 4 of treatment, week 8 and week 12 (EOT).

Collaborators and Investigators

• Sponsor: Molecure S.A.
• Investigators: Study Chair: Samson Fung, MD, CMO

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2024
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: December 13, 2023
• First Submitted That Met QC Criteria: January 3, 2024
• First Posted (Actual): January 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Sarcoidosis; Pulmonary Sarcoidosis; Chitinase
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Lung Diseases; Hypersensitivity; Lung Diseases, Interstitial; Hypersensitivity, Delayed; Sarcoidosis, Pulmonary; Sarcoidosis
• Other Study ID Numbers: OATD-01-C-03; 2023-506642-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No