5-(4-((2S,5S)-5-(4-CHLOROBENZYL)-2-METHYLMORPHOLINO)PIPERIDIN-1-YL)-1H- 1,2,4-TRIAZOL-3-AMINE for Pulmonary sarcoidosis

Inclusion criteria

• {"criterion_text":"- Male or female subject aged ≥18 years at Screening\n- 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: •\tBilateral hilar adenopathy (BHA) on any chest X-ray within 3 months or chest CT* within 12 months prior to enrolment OR •\tPerilymphatic 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.\n- 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)\n- Body Mass Index within the range of 18 - 46 kg/m2\n- 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: •\tWoman of nonchildbearing potential* •\tWoman 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: -\tcombined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation : \toral \tintravaginal \ttransdermal -\tprogestogen-only hormonal contraception associated with inhibition of ovulation: \toral \tinjectable \timplantable -\tintrauterine device -\tintrauterine hormone-releasing system -\tbilateral tubal occlusion -\tvasectomised partner** -\tsexual abstinence*** •\tMan 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.\n- Capable of understanding and complying with protocol requirements\n- Written informed consent given by the subject before the initiation of any study procedures Note: A witnessed consent is not all"}

Exclusion criteria

• {"criterion_text":"- 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.\n- Alcohol consumption above 20 units/week for men and 10 units/week for women\n- Known allergy to excipients of the study drug\n- Any contraindication to cardiac MRI and PET/CT procedures, including severe claustrophobia and known hypersensitivity to the contrast medium (limited to contraindication solely to PET/CT in case cardiac sarcoidosis is evaluated based on a pre-study cardiac MRI in line with the exclusion criterion no. 2)\n- Severe, uncontrolled systemic disease (e.g., clinically significant 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\n- Current smoker of >5 cigarettes or e-cigarettes per day or user of nicotine releasing alternatives (patches, chewing gums etc.)\n- Unable to take oral medications\n- History of or active Löfgren’s syndrome\n- Participation in another clinical study within 1 month prior to screening\n- 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\n- Concomitant use or need for treatment with a drug known for QT prolongation effect or a thiazide diuretic\n- 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)\n- 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)\n- 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\n- Known repeated demonstration of QTcF interval prolongation (>450 ms in a male and QTc >470 ms in a female) at Screening\n- Systemic or inhaled pharmacological treatment for sarcoidosis with: a.\tcorticosteroids/corticotropin: current treatment or received within 3 months prior to enrolment b.\tmethotrexate, 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\n- Primary systemic treatment indication being an extrapulmonary location of sarcoidosis (e.g., neurological)\n- Subjects currently treated with P-glycoprotein and/or BCRP strong inhibitors\n- Subjects currently treated with drugs that are sensitive substrates of OCT1, MATE1, MATE2K, OAT3 with a narrow therapeutic index\n- PET imaging, or other diagnostic or therapeutic procedure with administration of a radiopharmaceutical, performed within 6 weeks before Screening.\n- Known neurosarcoidosis or small fiber neuropathy or medical conditions causing primary ataxia\n- Subjects currently treated with pirfenidone or nintedanib\n- Cardiac sarcoidosis (known or diagnosed at Screening using cardiac Magnetic Resonance Imaging [MRI]) except for well documented currently inactive cardiac sarcoidosis Note: Cardiac sarcoidosis may be evaluated based solely on a pre-study cardiac MRI result if negative for active disease and performed not earlier than 12 months prior to enrollment, as long as no clinically relevant cardiac symptoms or signs (i.e., ECG abnormalities) developed since the time of this MRI\n- Hypokalemia (<3.6 mmol/L, mmol/L) or hypocalcemia (<2.1 mmol/L) at Screening\n- Marked fasting hyperglycemia or 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 separately provided PET protocol\n- Pregnancy, breastfeeding, or planning to become pregnant or breastfeed, oocyte or sperm donation and cryopreservation during the study and 7 months after EOT. For the purposes of detecting pregnancy occurrence after EOT, the Sponsor will provide urine pregnancy test to subjects to perform at home at monthly intervals after the end of the study last follow-up visit for up until 7 months post last administration of the study drug. The subjects will be advised to report to the sponsor any pregnancies occurring in that time.\n- Known positivity for Human Immunodeficiency Virus (HIV 1/2 antibodies), hepatitis B virus (HBV), or hepatitis C virus (HCV), or detected at screening\n- Subjects with psychiatric disorder that could affect the conduct of the study and/or compliance with the study treatment\n- Occurrence of Treatment-emerging Adverse Events (TEAEs), SAEs, Adverse Events of Special Interest (AESIs), TEAEs leading to discontinuation and TEAEs leading to death"}

Primary endpoints

• {"endpoint_text":"- Response to treatment from baseline to End-of-Treatment (EOT) (i.e., complete or partial response) using the criteria determined for each subject","definition_or_measurement_approach":"Response defined as reduction of granulomatous inflammation in pulmonary parenchyma evaluated by [18F]FDG PET/CT imaging; assessed from baseline to End-of-Treatment using criteria determined for each subject."}

Secondary endpoints

• {"endpoint_text":"- Granulomatous inflammation evaluated 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","definition_or_measurement_approach":"Quantified percent change in SUVmax, SUVmean, SUVpeak and lesion volumes on [18F]FDG PET/CT imaging."}
• {"endpoint_text":"- Absolute change in Forced Vital Capacity (FVC, % predicted) and Forced Expiratory Volume in the first second (FEV1)","definition_or_measurement_approach":"Absolute change from baseline in FVC (% predicted) and FEV1 measured by spirometry."}
• {"endpoint_text":"- Change in the quality of life measured by the Kings Sarcoidosis Questionnaire General and Lung (KSQ GENERAL and LUNG) scores","definition_or_measurement_approach":"Change from baseline in KSQ GENERAL and KSQ LUNG questionnaire scores."}
• {"endpoint_text":"- Occurrence of Treatment-emerging Adverse Events (TEAEs), SAEs, Adverse Events of Special Interest (AESIs), TEAEs leading to discontinuation and TEAEs leading to death","definition_or_measurement_approach":"Safety monitoring: incidence and characterization of TEAEs, SAEs, AESIs, and TEAEs leading to discontinuation or death."}
• {"endpoint_text":"- Occurrence of clinically significant laboratory (hematology and biochemistry) parameter abnormalities","definition_or_measurement_approach":"Incidence of clinically significant laboratory abnormalities in hematology and biochemistry parameters."}
• {"endpoint_text":"- Change in the Fatigue Assessment Scale total score","definition_or_measurement_approach":"Change from baseline in total score of the Fatigue Assessment Scale (FAS)."}
• {"endpoint_text":"- Mean change in vital signs (systolic and diastolic blood pressure, heart rate, respiratory rate) from baseline to each post-baseline evaluation time point","definition_or_measurement_approach":"Mean change from baseline in vital signs (SBP, DBP, HR, RR) at scheduled post-baseline visits."}
• {"endpoint_text":"- Occurrence of any clinically significant abnormalities in 12- lead electrocardiography (ECG) or 24-h ECG","definition_or_measurement_approach":"Incidence of clinically significant abnormalities on 12-lead ECG or 24-h ECG monitoring."}
• {"endpoint_text":"- Change from baseline and in between visits in cardiac safety parameters evaluated by 12-lead ECG [Heart Rate (HR) , PR QTcF and QRS]","definition_or_measurement_approach":"Change from baseline and between visits in HR, PR, QTcF and QRS intervals measured by 12-lead ECG."}
• {"endpoint_text":"- Heart rhythm abnormalities including supraventricular arrhythmias, ventricular arrhythmias, and non-sustained ventricular tachycardias","definition_or_measurement_approach":"Incidence and characterization of cardiac rhythm abnormalities (supraventricular and ventricular arrhythmias, non-sustained VT) detected by ECG/24-h monitoring."}
• {"endpoint_text":"- Occurrence of a clinically significant abnormality of sperm parameters","definition_or_measurement_approach":"Incidence of clinically significant abnormalities in semen parameters (sperm analysis) in male subjects."}
• {"endpoint_text":"- Occurrence of clinically significant abnormality of free testosterone concentration","definition_or_measurement_approach":"Incidence of clinically significant abnormalities in free testosterone concentration in male subjects."}
• {"endpoint_text":"- Occurrence of TEAEs of sensation abnormalities or ataxia","definition_or_measurement_approach":"Incidence of treatment-emergent adverse events involving sensory abnormalities or ataxia."}
• {"endpoint_text":"- 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)]","definition_or_measurement_approach":"Proportion of subjects with clinically significant abnormalities in TSH, FT3, FT4 and renal function parameters (BUN/urea, creatinine, CrCL)."}
• {"endpoint_text":"- Mean plasma concentrations of OATD-01 measured at various timepoints post-baseline (sparse sampling)","definition_or_measurement_approach":"Mean plasma concentrations of OATD-01 at scheduled PK sampling timepoints (sparse sampling) to characterize PK exposure."}

Methods

• Organic Facebook posts (social media organic content) — country-specific organic posts documents present (e.g., Germany, Greece, Norway, Netherlands).
• Paid Facebook/Instagram advertisements (social media paid ads) — country-specific paid ad materials present (e.g., Germany, Greece, Norway).
• Website recruitment (study/landing page design) — country-specific website design documents present.
• Patient leaflets and printed materials (patient leaflets, pocket ECG patient guide, patient ID card) — multilingual patient leaflets available (Germany, Greece, France, Denmark, Norway, Netherlands).
• Privacy notices and patient-facing informational materials (privacy notice documents per country) — country-specific privacy notice documents.
• Recruitment procedures/K1 documents (country-specific recruitment procedures K1_DE, K1_GR, K1_NO, K1_DK, K1_Recruitment arrangements_NL, K1_FR) describing local recruitment arrangements.

Germany

Earliest CTIS Part Ii Submission Date

02-05-2024

Latest Decision Or Authorization Date

10-04-2025

Processing Time Days

343

Number Of Sites

3

Number Of Participants

10

Greece

Earliest CTIS Part Ii Submission Date

20-02-2024

Latest Decision Or Authorization Date

02-05-2025

Processing Time Days

436

Number Of Sites

4

Number Of Participants

15

Netherlands

Earliest CTIS Part Ii Submission Date

30-07-2025

Latest Decision Or Authorization Date

14-08-2025

Processing Time Days

15

Number Of Sites

2

Number Of Participants

15

Denmark

Earliest CTIS Part Ii Submission Date

10-05-2024

Latest Decision Or Authorization Date

20-10-2025

Processing Time Days

529

Number Of Sites

1

Number Of Participants

4

France

Earliest CTIS Part Ii Submission Date

06-05-2024

Latest Decision Or Authorization Date

06-11-2025

Processing Time Days

518

Number Of Sites

4

Number Of Participants

10

Norway

Earliest CTIS Part Ii Submission Date

18-04-2024

Latest Decision Or Authorization Date

24-02-2026

Processing Time Days

313

Number Of Sites

2

Number Of Participants

17

Primary sponsor

Full Name

Molecure S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Poland

Third parties

• {"country":"Greece","full_name":"Κα Ανατολή Αμπεριάδου","duties_or_roles":"Codes: 1","organisation_type":"Industry"}
• {"country":"France","full_name":"Orion Sante","duties_or_roles":"Codes: 1,10,11,12,13,2,5,6,8,9","organisation_type":"Pharmaceutical company"}