2023-506642-23-01
Recruiting
Phase 2
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)
Molecure S.A.16 sites in 7 countries52 target enrollmentStarted: May 16, 2024Last updated:
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Molecure S.A.
- Enrollment
- 52
- Locations
- 16
- Primary Endpoint
- Response to treatment from baseline to End-of-Treatment (EOT) (i.e., complete or partial response) using the criteria determined for each subject
Overview
Brief Summary
To evaluate the response to a 12-week treatment with OATD-01 as a reduction of granulomatous inflammation in pulmonary parenchyma evaluated by [18F]FDG PET/CT imaging in subjects with active pulmonary sarcoidosis
Eligibility Criteria
- Ages
- 18 years to 64 years (18-64 Years)
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Male or female subject aged ≥18 years at Screening
- •Diagnosis of active and currently symptomatic pulmonary sarcoidosis, either treatment-naïve or previously treated but currently untreated, with diagnostic criteria adapted from Official American Thoracic Society Clinical Practice Guideline 2020 and with limitations described in the exclusion criteria section: • Bilateral hilar adenopathy (BHA) on any chest X-ray within 3 months or chest CT* within 12 months prior to enrolment OR • Perilymphatic nodules, peribronchial thickening (on chest CT*), or upper lobe or diffuse infiltrates (on any chest imaging) within 3 months prior to enrolment and at least one of the three: - known previous positive biopsy from any body site showing pathologic features consistent with sarcoidosis, obtained at any point in the past - history of or active Lupus pernio or Heerfordt’s syndrome positive BAL result with the ratio of CD4+ to CD8+ T-lymphocytes higher than 3.5 supported by a documented positive opinion on diagnosis of sarcoidosis by an independent expert, assigned by sponsor, based on a highly suggestive clinical and radiological picture * to avoid CT-derived excessive cumulative radiation, a minimum interval of 12 weeks (or longer as defined by local standards) is to be respected between any chest (High Resolution-)CT performed pre-study before the informed consent and the planned baseline [18F]FDG PET/CT at screening.
- •Parenchymal pulmonary involvement evidenced by [ 18F]FDG PET/CT imaging at Screening (or performed at the study site within 3 months prior to enrolment under certain conditions detailed in section 7.2.2.8)
- •Body Mass Index within the range of 18 - 46 kg/m2
- •Subjects willing to avoid pregnancy or fathering a child and agree to use acceptable effective methods of birth control (per recommendations from Heads of Medicines Agencies - Clinical Trials Facilitation and Coordination Group) defined as those, alone or in combination, that result in a low failure rate for the entire duration of the study including: • Woman of nonchildbearing potential* • Woman of childbearing potential* who has a negative serum pregnancy test at Screening and at any timepoint before the first study drug dose on Day 1 and who agrees to take highly effective contraceptive measure to avoid pregnancy (with a failure rate of less than 1% per year when used consistently and correctly) from Screening until 7 months after EOT. As highly effective contraceptive measures are considered: - combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation : oral intravaginal transdermal - progestogen-only hormonal contraception associated with inhibition of ovulation: oral injectable implantable - intrauterine device - intrauterine hormone-releasing system - bilateral tubal occlusion - vasectomised partner** - sexual abstinence*** • Man who agrees to use double barrier contraception (condoms - or diaphragm/ cervical cap used by their female partner- plus spermicidal agent: foam, gel, film etc.) to avoid fathering a child from Screening until 100 days after EOT, or is surgically sterilized. *A woman is considered of childbearing potential i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. **Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the surgical success. ***Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
- •Capable of understanding and complying with protocol requirements
- •Written informed consent given by the subject before the initiation of any study procedures Note: A witnessed consent is not all
Exclusion Criteria
- •Severity and/or phenotype of sarcoidosis requiring immediate (or within the next 3 months) initiation of treatment with a corticosteroid, corticotropin, methotrexate, anti-TNF agent, azathioprine, JAK inhibitor, mycophenolate, or leflunomide.
- •Subject deprived of liberty by a judicial or administrative decision, subject admitted to a social institution or who is under a measure of legal protection, subject hospitalized without consent or who is in an emergency situation
- •Established alternative diagnosis of a non-infectious or infectious systemic disease, or suspicion thereof, undermining the suspicion/diagnosis of sarcoidosis
- •Total serum bilirubin >1.5 x upper limit of normal (ULN), with the exception of previously documented Gilbert syndrome, or alanine aminotransferase (ALT) or asparagine aminotransferase (AST) > 2.5 x ULN, or alkaline phosphatase (ALP) >1.5 x ULN, or liver failure and/or cirrhosis or subjects with moderate to severe hepatic impairment (i.e., Child-Pugh score ≥7)
- •If performed pre-study, mediastinal and/or hilar lymph node biopsy result suggestive of an alternative diagnosis to sarcoidosis (taking into account the Key Pathological Features of Sarcoidosis by the Official American Thoracic Society Clinical Practice Guideline 2020)
- •Clinically significant lung disease other than sarcoidosis (including but not limited to tuberculosis, asthma, Chronic Obstructive Pulmonary Disease, interstitial lung disease, lung cancer) or any current inflammatory or immunological systemic disease other than sarcoidosis
- •Known repeated demonstration of QTcF interval prolongation (>450 ms in a male and QTc >470 ms in a female) at Screening
- •Systemic or inhaled pharmacological treatment for sarcoidosis with: a. corticosteroids/corticotropin: current treatment or received within 3 months prior to enrolment b. methotrexate, anti-TNF agents, azathioprine, JAK inhibitors, mycophenolate, leflunomide, or any investigational therapy that is potentially disease-modifying: current treatment or received within 4 months prior to enrolment
- •Primary systemic treatment indication being an extrapulmonary location of sarcoidosis (e.g., neurological)
- •Subjects currently treated with P-glycoprotein and/or BCRP strong inhibitors
Outcomes
Primary Outcomes
Response to treatment from baseline to End-of-Treatment (EOT) (i.e., complete or partial response) using the criteria determined for each subject
Response to treatment from baseline to End-of-Treatment (EOT) (i.e., complete or partial response) using the criteria determined for each subject
Secondary Outcomes
- Granulomatous inflammation evaluated by [18F]FDG PET/CT imaging, quantified as the percent change of maximum, mean, peak SUV (SUVmax, SUVmean, SUVpeak), DocuSign Envelope ID: F57C5576-6512-4FF0-BFC4-DC20E82978C1 Study code OATD-01-C-03 Version 1.0, 21 June 2023 Confidential Clinical Study Protocol Page 9 of 75 and volume of the lesions in pulmonary parenchyma, mediastinal/hilar nodes, and extrathoracic locations
- Absolute change in Forced Vital Capacity (FVC, % predicted) and Forced Expiratory Volume in the first second (FEV1)
- Change in the quality of life measured by the Kings Sarcoidosis Questionnaire General and Lung (KSQ GENERAL and LUNG) scores
- Occurrence of Treatment-emerging Adverse Events (TEAEs), SAEs, Adverse Events of Special Interest (AESIs), TEAEs leading to discontinuation and TEAEs leading to death
- Occurrence of clinically significant laboratory (hematology and biochemistry) parameter abnormalities
- Change in the Fatigue Assessment Scale total score
- Mean change in vital signs (systolic and diastolic blood pressure, heart rate, respiratory rate) from baseline to each post-baseline evaluation time point
- Occurrence of any clinically significant abnormalities in 12- lead electrocardiography (ECG) or 24-h ECG
- Change from baseline and in between visits in cardiac safety parameters evaluated by 12-lead ECG [Heart Rate (HR) , PR QTcF and QRS]
- Heart rhythm abnormalities including supraventricular arrhythmias, ventricular arrhythmias, and non-sustained ventricular tachycardias
- Occurrence of a clinically significant abnormality of sperm parameters
- Occurrence of clinically significant abnormality of free testosterone concentration
- Occurrence of TEAEs of sensation abnormalities or ataxia
- 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)]
- Mean plasma concentrations of OATD-01 measured at various timepoints post-baseline (sparse sampling)
Investigators
Theodore Charitos
Scientific
Molecure S.A.
Study Sites (16)
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