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

Официальное название

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)

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (12)

• Total granulomatous inflammation evaluation [Срок оценки: After 12 weeks of treatment, i.e. from baseline (randomization) visit to EOT visit.]
• Pulmonary function Forced Vital Capacity (FVC) [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: Assessed at baseline (randomization) visit and after 12 weeks of treatment (EOT visit) or study participation (week 12 visit).]
• Fatigue Assessment Scale (FAS) [Срок оценки: Assessed at baseline (randomization) visit and after 12 weeks of treatment (EOT visit) or study participation (week 12 visit).]
• Adverse events [Срок оценки: Recorded from the time of signature of informed consent and until 30 days after the last dose of OATD-01/Placebo.]
• Laboratory tests [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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.]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 7 центров

• 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

Великобритания · 5 центров

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

Франция · 4 центра

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

Греция · 4 центра

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

Германия · 3 центра

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

Нидерланды · 2 центра

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

Норвегия · 2 центра

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

Дания · 1 центр

• Molecure Investigative Site — Vejle

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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