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

Official title

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

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.

Interventions

• Drug OATD-01
  OATD-01 is an oral inhibitor of chitinase-1 (CHIT1)
• Drug Placebo
  Matching placebo tablets

Primary outcome measures

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

Secondary outcome measures (12)

• Total granulomatous inflammation evaluation [Time frame: After 12 weeks of treatment, i.e. from baseline (randomization) visit to EOT visit.]
• Pulmonary function Forced Vital Capacity (FVC) [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) [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 [Time frame: Assessed at baseline (randomization) visit and after 12 weeks of treatment (EOT visit) or study participation (week 12 visit).]
• Fatigue Assessment Scale (FAS) [Time frame: Assessed at baseline (randomization) visit and after 12 weeks of treatment (EOT visit) or study participation (week 12 visit).]
• Adverse events [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 [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 [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 [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 [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 [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 [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.]

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
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 7 centers

• Molecure Investigative Site — Birmingham
• Molecure Investigative Site — Kansas City
• Molecure Investigative Site — Baltimore
• Molecure Investigative Site — Rochester
• Molecure Investigative Site — Cleveland
• Molecure Investigative Site — Philadelphia
• Molecure Investigative Site — Charleston

United Kingdom · 5 centers

• Molecure Investigative Site — Birmingham
• Molecure Investigative Site — Cambridge
• Molecure Investigative Site — Edinburgh
• Molecure Investigative Site — London
• Molecure Investigative Site — London

France · 4 centers

• Molecure Investigative Site — Bobigny
• Molecure Investigative Site — Montpellier
• Molecure Investigative Site — Paris
• Molecure Investigative Site — Paris

Greece · 4 centers

• Molecure Investigative Site — Corfu
• Molecure Investigative Site — Heraklion
• Molecure Investigative Site — Pátrai
• Molecure Investigative Site — Thessaloniki

Germany · 3 centers

• Molecure Investigative Site — Essen
• Molecure Investigative Site — Freiburg im Breisgau
• Molecure Investigative Site — Mainz-GE

Netherlands · 2 centers

• Molecure Investigative Site — Nieuwegein
• Molecure Investigative Site — Rotterdam

Norway · 2 centers

• Molecure Investigative Site — Bergen
• Molecure Investigative Site — Oslo

Denmark · 1 center

• Molecure Investigative Site — Vejle

Identifiers

NCT: NCT06205121 · OATD-01-C-03 · 2023-506642-23

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗