A Study to Investigate the Safety, Tolerability and Pharmacokinetics of TB-840 in Healthy Subjects

Study Overview
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Brief Summary
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TB-840(Agonist of RORα) is a candidate for NASH treatment that activates RORα(Retinoid-related orphan receptor) and its target validation for RORα and potential as a NASH treatment. This study is a dose block-randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study. For each dose group, 6 subjects will be randomly assigned to the test group (TB-840) and 2 subjects will be randomly assigned to the control group (placebo). Adverse event (AE) monitoring, physical examination, vital signs, ECG, clinical laboratory test will be done for safety and tolerability assessment, and blood and urine samples will be collected for Pharmacokinetic (PK) assessment.

Official Title
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A Dose Block-randomized, Double-blind, Placebo Controlled, Single-/Multiple-dosing, Dose-escalation Phase 1 Clinical Trial to Investigate the Safety, Tolerability, Pharmacokinetic Characteristics of TB-840 (NASH Treatment Candidate) After Oral Administration in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Comparison of TB-840 treatment with Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults aged ≥ 19 and ≤ 45 years at the time of screening visit BMI of ≥ 18.0 and ≤ 27.0 kg/m2 at the time of screening visit Clinically confirmed as healthy based on the medical history, physical examination, vital signs, electrocardiography (ECG), and proper laboratory tests (Subjects with values out of the normal range may participate in the study if they are deemed clinically insignificant by the investigator.) Agree to use medically acceptable methods of contraception by participant, his/her spouse, or partner and not to donate sperm or oocyte from the date of the first dose of the investigational product (IP) until 90 days after the last dose of the IP Examples of medically acceptable methods of contraception Females (females who use oral hormonal contraceptives and subcutaneous hormonal contraceptive implants may be excluded from the study) Use of an intrauterine device with a proven pregnancy failure rate Use of barrier method with spermicide Surgical sterilization (salpingectomy/tubal ligation, hysterectomy, etc.) Males Use of barrier method with spermicide Surgical sterilization (vasectomy, vasoligation, etc.) Voluntarily decided to participate in the study and provided written consent to comply with the protocol Exclusion Criteria: Current or history of a clinically significant hepatic, renal, gastrointestinal, respiratory, musculoskeletal, endocrine, neuropsychiatric, hemato-oncological, or cardiovascular disease History of gastrointestinal diseases (e.g., Crohn's disease, ulcer, etc.) or surgery (excluding simple appendectomy or hernia repair) that may affect the absorption of the investigational products History of clinically significant hypersensitivity to drugs containing RORα agonist or other ingredients of the same class, or other drugs (aspirin and non-steroidal anti-inflammatory drugs, antibiotics, etc.) History of drug abuse or positive result from urine drug screening of drugs with concerns of drug abuse Subjects with any of the following results at the time of screening visit: Systolic blood pressure: < 90 mmHg or > 140 mmHg Diastolic blood pressure: < 50 mmHg or > 90 mmHg Heart rate: < 50 bpm or > 100 bpm AST: > x 1.5 ULN ALT: > x 1.5 ULN ALP: > x 1.5 ULN T.bil: > x 1.5 ULN γ-GT： > x 1.5 ULN Serum creatinine: > x 1.5 ULN Participated in another bioequivalence study or clinical study and have been exposed to an investigational product within 6 months prior to the date of the first dose of this study Donated whole blood within 2 months or blood components within 1 month, or received blood transfusion within 1 month prior to the date of the first dose of this study Use of drug-metabolizing enzyme inducer or inhibitor such as barbiturates within 1 month prior to the date of the first dose of this study Consumption of caffeine- or grapefruit-containing foods or beverages within 3 days prior to the date of the first dose of this study Use of any prescription drugs or herbal medicines within 1 month, or any over-the-counter (OTC) drugs within 1 week prior to the date of the first dose of this study (Subjects may participate in the study if such use is judged not to significantly affect the assessment of safety and pharmacokinetics by the investigator.) Excessive intake of caffeine, excessive intake of alcohol, or heavy smoking (caffeine > 5 units/day, alcohol > 21 units/week [1 unit = 10 mL of pure alcohol], smoking > 10 cigarettes/day) Unable to consume meals provided by the study site Prior participation in this study Positive result in serology tests (hepatitis B tests, human immunodeficiency virus [HIV] tests, hepatitis C tests, or syphilis tests [RPR]) Determined inappropriate for the study by the investigator

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 Single Dose SD1 (first dose)<br>Group SD1 a first single dose of TB-840(n=6) or placebo(n=2) | Drug: Comparison of TB-840 treatment with Placebo<br>* Single dose or Multiple Dose of TB-840 treatment<br>* Other names: TB-840;|
| Experimental: Cohort 2 Single Dose SD2 (second dose)<br>Group SD2 a first single dose of TB-840(n=6) or placebo(n=2) | Drug: Comparison of TB-840 treatment with Placebo<br>* Single dose or Multiple Dose of TB-840 treatment<br>* Other names: TB-840;|
| Experimental: Cohort 3 Single Dose SD3 (third dose)<br>Group SD3 a first single dose of TB-840(n=6) or placebo(n=2) | Drug: Comparison of TB-840 treatment with Placebo<br>* Single dose or Multiple Dose of TB-840 treatment<br>* Other names: TB-840;|
| Experimental: Cohort 4 Single Dose SD4 (fourth dose)<br>Group SD4 a first single dose of TB-840(n=6) or placebo(n=2) | Drug: Comparison of TB-840 treatment with Placebo<br>* Single dose or Multiple Dose of TB-840 treatment<br>* Other names: TB-840;|
| Experimental: Cohort 5 Single Dose SD5 (fifth dose)<br>Group SD5 a first single dose of TB-840(n=6) or placebo(n=2) | Drug: Comparison of TB-840 treatment with Placebo<br>* Single dose or Multiple Dose of TB-840 treatment<br>* Other names: TB-840;|
| Experimental: Cohort 6 Single Dose SD6 (sixth dose)<br>Group SD6 a first single dose of TB-840(n=6) or placebo(n=2) | Drug: Comparison of TB-840 treatment with Placebo<br>* Single dose or Multiple Dose of TB-840 treatment<br>* Other names: TB-840;|
| Experimental: Cohort 7 Single Dose SD7 (seventh dose)<br>Group SD7 a first single dose of TB-840(n=6) or placebo(n=2) | Drug: Comparison of TB-840 treatment with Placebo<br>* Single dose or Multiple Dose of TB-840 treatment<br>* Other names: TB-840;|
| Experimental: Cohort 8 Single Dose SD8 (eighth dose)<br>Group SD8 a first single dose of TB-840(n=6) or placebo(n=2) | Drug: Comparison of TB-840 treatment with Placebo<br>* Single dose or Multiple Dose of TB-840 treatment<br>* Other names: TB-840;|
| Experimental: Cohort 9 : Mutiple Dose MD1<br>Group MD1 a first multiple dose of TB-840(n=6) or placebo(n=2) | Drug: Comparison of TB-840 treatment with Placebo<br>* Single dose or Multiple Dose of TB-840 treatment<br>* Other names: TB-840;|
| Experimental: Cohort 10 : Mutiple Dose MD2<br>Group MD2 a first multiple dose of TB-840(n=6) or placebo(n=2) | Drug: Comparison of TB-840 treatment with Placebo<br>* Single dose or Multiple Dose of TB-840 treatment<br>* Other names: TB-840;|
| Experimental: Cohort 11 : Mutiple Dose MD3<br>Group MD3 a first multiple dose of TB-840(n=6) or placebo(n=2) | Drug: Comparison of TB-840 treatment with Placebo<br>* Single dose or Multiple Dose of TB-840 treatment<br>* Other names: TB-840;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.03 | Incidences of treatment-emergent adverse events | Up to 10 days from single ascending dose | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.03 | Incidences of treatment-emergent adverse events | Up to 14 days from multiple ascending dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration of drug in plasma[Cmax] | Pharmacokinetic Profile of TB-840 | Up to 4 days from single ascending dose | 
| Maximum concentration of drug in plasma[Cmax] | Pharmacokinetic Profile of TB-840 | Up to 8 days from multiple ascending dose | 
| Area under the plasma drug concentration-time curve[AUC] | Pharmacokinetic Profile of TB-840 | Up to 4 days from single ascending dose | 
| Area under the plasma drug concentration-time curve[AUC] | Pharmacokinetic Profile of TB-840 | Up to 8 days from multiple ascending dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Retinoid-related orphan receptor alpha, RORα, Agonist of RORα