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

NCT05045534 | Completed Phase 1

• 1 other identifier: TB-840-PRT-01
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Keywords

Retinoid-related orphan receptor alpha; RORα; Agonist of RORα

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Maximum concentration of drug in plasma[Cmax]

  Up to 4 days from single ascending dose

• Maximum concentration of drug in plasma[Cmax]

  Up to 8 days from multiple ascending dose

• Area under the plasma drug concentration-time curve[AUC]

  Up to 4 days from single ascending dose

• Area under the plasma drug concentration-time curve[AUC]

  Up to 8 days from multiple ascending dose

Study Arms (11)

Cohort 1 Single Dose SD1 (first dose)

EXPERIMENTAL

Group SD1 a first single dose of TB-840(n=6) or placebo(n=2)

Drug: Comparison of TB-840 treatment with Placebo

Cohort 2 Single Dose SD2 (second dose)

EXPERIMENTAL

Group SD2 a first single dose of TB-840(n=6) or placebo(n=2)

Drug: Comparison of TB-840 treatment with Placebo

Cohort 3 Single Dose SD3 (third dose)

EXPERIMENTAL

Group SD3 a first single dose of TB-840(n=6) or placebo(n=2)

Drug: Comparison of TB-840 treatment with Placebo

Cohort 4 Single Dose SD4 (fourth dose)

EXPERIMENTAL

Group SD4 a first single dose of TB-840(n=6) or placebo(n=2)

Drug: Comparison of TB-840 treatment with Placebo

Cohort 5 Single Dose SD5 (fifth dose)

EXPERIMENTAL

Group SD5 a first single dose of TB-840(n=6) or placebo(n=2)

Drug: Comparison of TB-840 treatment with Placebo

Cohort 6 Single Dose SD6 (sixth dose)

EXPERIMENTAL

Group SD6 a first single dose of TB-840(n=6) or placebo(n=2)

Drug: Comparison of TB-840 treatment with Placebo

Cohort 7 Single Dose SD7 (seventh dose)

EXPERIMENTAL

Group SD7 a first single dose of TB-840(n=6) or placebo(n=2)

Drug: Comparison of TB-840 treatment with Placebo

Cohort 8 Single Dose SD8 (eighth dose)

EXPERIMENTAL

Group SD8 a first single dose of TB-840(n=6) or placebo(n=2)

Drug: Comparison of TB-840 treatment with Placebo

Cohort 9 : Mutiple Dose MD1

EXPERIMENTAL

Group MD1 a first multiple dose of TB-840(n=6) or placebo(n=2)

Drug: Comparison of TB-840 treatment with Placebo

Cohort 10 : Mutiple Dose MD2

EXPERIMENTAL

Group MD2 a first multiple dose of TB-840(n=6) or placebo(n=2)

Drug: Comparison of TB-840 treatment with Placebo

Cohort 11 : Mutiple Dose MD3

EXPERIMENTAL

Group MD3 a first multiple dose of TB-840(n=6) or placebo(n=2)

Drug: Comparison of TB-840 treatment with Placebo

Interventions

Comparison of TB-840 treatment with Placebo DRUG

Single dose or Multiple Dose of TB-840 treatment

Also known as: TB-840

Cohort 1 Single Dose SD1 (first dose); Cohort 10 : Mutiple Dose MD2; Cohort 11 : Mutiple Dose MD3; Cohort 2 Single Dose SD2 (second dose); Cohort 3 Single Dose SD3 (third dose); Cohort 4 Single Dose SD4 (fourth dose); Cohort 5 Single Dose SD5 (fifth dose); Cohort 6 Single Dose SD6 (sixth dose); Cohort 7 Single Dose SD7 (seventh dose); Cohort 8 Single Dose SD8 (eighth dose); Cohort 9 : Mutiple Dose MD1

Eligibility Criteria

• Age: 19 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Therasid Bioscience: lead

Study Sites (1)

Therasid Bioscience

Seongnam-si, Gyeonggi-do, 13488, South Korea

Location

Related Publications (1)

• Hwang I, Lee SR, Kim HJ, Kim Y, Lee SW. Safety, Pharmacokinetics, and Food Effect of the RORalpha Agonist TB-840, a Novel Candidate for Metabolic Dysfunction-Associated Steatohepatitis (MASH): A Randomized First-in-Human Study in Healthy Volunteers. Life (Basel). 2025 Sep 7;15(9):1410. doi: 10.3390/life15091410.

  PMID: 41010352 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2021
• First Posted: September 16, 2021
• Study Start: September 14, 2021
• Primary Completion: August 29, 2022
• Study Completion: December 30, 2022
• Last Updated: August 1, 2023

Record last verified: 2023-07

Locations

KR (1)