Clinical trial NCT06205121: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pulmonary Sarcoidosis
Keywords: Pulmonary Sarcoidosis
Sarcoidosis
Chitinase
Lead sponsor: Molecure S.A.
Sponsor class: INDUSTRY
First posted: 2024-01-12
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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
* 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 \&lt;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 (\&lt;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 \&gt;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 \&gt;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.

Primary outcomes:
measure: Response to treatment
timeFrame: After 12 weeks of treatment, i.e. from baseline (randomization) visit to End-of-Treatment (EOT) visit.
Secondary outcomes:
measure: Total granulomatous inflammation evaluation
timeFrame: After 12 weeks of treatment, i.e. from baseline (randomization) visit to EOT visit.
measure: Pulmonary function Forced Vital Capacity (FVC)
timeFrame: At Screening visit and over 12 weeks of treatment - at baseline (randomization) visit, at week 4 of treatment, week 8 and week 12 (EOT).
measure: Pulmonary function Forced Expiratory Volume in the first second (FEV1)
timeFrame: At Screening visit and over 12 weeks of treatment - at baseline (randomization) visit, at week 4 of treatment, week 8 and week 12 (EOT).
measure: Quality of life assessment
timeFrame: Assessed at baseline (randomization) visit and after 12 weeks of treatment (EOT visit) or study participation (week 12 visit).
measure: Fatigue Assessment Scale (FAS)
timeFrame: Assessed at baseline (randomization) visit and after 12 weeks of treatment (EOT visit) or study participation (week 12 visit).
measure: Adverse events
timeFrame: Recorded from the time of signature of informed consent and until 30 days after the last dose of OATD-01/Placebo.
measure: Laboratory tests
timeFrame: 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).
measure: Vital signs - Systolic Blood Pressure
timeFrame: 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
measure: Vital signs - Diastolic Blood Pressure
timeFrame: 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.
measure: Vital signs
timeFrame: 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.
measure: Vital signs - Respiratory Rate
timeFrame: 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
measure: Electrocardiography
timeFrame: 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.
measure: Electrocardiography - specific parameters
timeFrame: 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.
measure: Male fertility
timeFrame: Measured at baseline (randomization) visit and at week 8 or week 12 (EOT) of treatment.
measure: Neurological status
timeFrame: 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
measure: Thyroid and renal function
timeFrame: Clinically significant abnormalities detected during 12 weeks of treatment - at baseline (randomization) visit, at week 4 of treatment, week 8 and week 12 (EOT).
measure: Pharmacokinetics assessment
timeFrame: Measured during 2 weeks of treatment - at baseline (randomization) visit, at week 4 of treatment, week 8 and week 12 (EOT).
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Molecure Investigative Site
state: Alabama
city: Kansas City
country: United States
facility: Molecure Investigative Site
state: Kansas
city: Baltimore
country: United States
facility: Molecure Investigative Site
state: Maryland
city: Rochester
country: United States
facility: Molecure Investigative Site
state: Minnesota
city: Cleveland
country: United States
facility: Molecure Investigative Site
state: Ohio
city: Philadelphia
country: United States
facility: Molecure Investigative Site
state: Pennsylvania
city: Charleston
country: United States
facility: Molecure Investigative Site
state: South Carolina
city: Vejle
country: Denmark
facility: Molecure Investigative Site
city: Bobigny
country: France
facility: Molecure Investigative Site
city: Paris
country: France
facility: Molecure Investigative Site
city: Paris
country: France
facility: Molecure Investigative Site
city: Essen
country: Germany
facility: Molecure Investigative Site
city: Freiburg
country: Germany
facility: Molecure Investigative Site
city: Mainz-GE
country: Germany
facility: Molecure Investigative Site
city: Corfu
country: Greece
facility: Molecure Investigative Site
city: Heraklion
country: Greece
facility: Molecure Investigative Site
city: Thessaloníki
country: Greece
facility: Molecure Investigative Site
city: Bergen
country: Norway
facility: Molecure Investigative Site
city: Oslo
country: Norway
facility: Molecure Investigative Site
city: Birmingham
country: United Kingdom
facility: Molecure Investigative Site
city: Cambridge
country: United Kingdom
facility: Molecure Investigative Site
city: Edinburgh
country: United Kingdom
facility: Molecure Investigative Site
city: London
country: United Kingdom
facility: Molecure Investigative Site
city: London
country: United Kingdom
facility: Molecure Investigative Site
Study officials:
affiliation: CMO
name: Piotr Iwanowski, MD
role: STUDY_CHAIR
References: