A study to evaluate single and multiple doses of TLC-1180 in healthy subjects
| ISRCTN | ISRCTN21589167 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN21589167 |
| Secondary identifying numbers | 1180-CL-101 |
- Submission date
- 16/10/2025
- Registration date
- 17/10/2025
- Last edited
- 20/10/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Other
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Background and study aims
This study aims to test a new drug, TLC-1180, compared with a placebo at different doses, to find out if it is safe and to understand the way people process the drug. A placebo looks like a drug but has no active ingredient.
Who can participate?
Healthy male and non-pregnant, non-lactating female subjects, 18-55 years of age, inclusive.
What does the study involve?
Participants are randomly assigned to receive either TLC-1180 or a placebo as a single dose or multiple doses to determine the safety and the way people process the drug. The total maximum study duration for participants is about 53 days.
What are the possible benefits and risks of participating?
Participants are not expected to receive any direct benefits from the study, but the information that is learned may help other people in the future. TLC-1180 has not yet been tested in humans. This is the first trial of TLC-1180 in humans. For this reason, the side effects of this drug are not known at this time.
Where is the study run from?
OrsoBio, Inc. (USA)
When is the study starting and how long is it expected to run for?
October 2025 to November 2026
Who is funding the study?
OrsoBio, Inc. (USA)
Who is the main contact?
Clinicaltrials_Inquires@orsobio.com
Contact information
Dr Clinical Trials
Public, Scientific, Principal investigator
Public, Scientific, Principal investigator
101 Jefferson Drive
Menlo Park
94025
United States of America
| Phone | +1 650-382-2225 |
|---|---|
| Clinicaltrials_Inquires@orsobio.com |
Study information
| Study design | Single-centre double-blind randomized placebo-controlled single- and multiple-ascending-dose and open-label study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Other, Safety |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A phase 1 study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending doses of TLC-1180 in healthy subjects and an open-label assessment of the relative bioavailability of, and effect of food on, a tablet formulation of TLC-1180 |
| Study objectives | The primary objectives are to assess the safety, tolerability, and pharmacokinetics of TLC-1180 in healthy subjects. The exploratory objective is to evaluate the pharmacodynamics of TLC-1180 in healthy subjects. |
| Ethics approval(s) |
Approved 10/10/2025, Northern A Health and Disability Ethics Committee (HDEC) (Ministry of Health, PO Box 5013, Wellington, 6140, New Zealand; +64 4 819 6877; hdecs@health.govt.nz), ref: 2025 FULL 23746 |
| Health condition(s) or problem(s) studied | Healthy volunteers |
| Intervention | The study will proceed in four parts (Parts A-D), where Parts A-C are randomized, blinded (sponsor-unblinded), placebo-controlled, and Part D is open-label. Part A will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of escalating single oral doses of TLC-1180 or matching placebo over 5 cohorts (within each cohort, 8 subjects will be randomized 3:1 to receive either blinded TLC-1180 or placebo-to-match [PTM]). To maximize subject safety, in single-ascending dose (SAD) cohorts in Part A, two sentinel subjects (one randomized to TLC-1180 and one to PTM) will be dosed, and safety and tolerability data will be evaluated before dosing of the remaining subjects in each cohort. Within SAD cohorts in Part A and C, initiation of single-dose administration at escalating dose levels will be based on recommendations by the Safety Review Committee (SRC), where the SRC will evaluate cumulative safety data, and relevant and available PK and/or PD data, following single-dose administration of the previous dosing cohort. Part B will evaluate the safety, tolerability, PK, and PD of escalating multiple doses of TLC-1180 or matching placebo over 5 cohorts (within each cohort, 10 subjects will be randomized 4:1 to receive either blinded TLC-1180 or PTM) for 14 days. The dose for the first multiple-ascending dose (MAD) cohort will be selected such that predicted steady-state exposure (Cmax and AUCtau) will not exceed single dose exposures (Cmax and AUCinf) observed in the highest dose Part A SAD cohort considered safe and well tolerated based on evaluation of cumulative safety, tolerability, and any relevant and available PK and/or PD data from all subjects enrolled in prior relevant SAD cohort(s). For the remaining Part B cohorts, dose selection and initiation of additional Part B MAD cohorts will be based on recommendation by the SRC, where the SRC will evaluate cumulative safety, tolerability, and any relevant and available PK and/or PD data from all subjects enrolled in prior MAD cohort(s), as well as all subjects enrolled in prior SAD cohort(s) which evaluated doses with associated exposure (Cmax and AUCinf) equal to or greater than expected (Cmax and AUCtau) at the proposed Part B MAD cohort dose. Additionally, any dose selected for evaluation in Part B will not exceed a 3-fold increase in dose or expected exposure relative to the highest dose previously evaluated. Part C of the study is designed to be adaptive, based on initial data from Parts A and/or B, to evaluate the safety, tolerability, PK, and PD of TLC-1180, with adaptive dose selection, administered as a single dose or multiple doses over 14 days. The SRC will oversee dose selection and escalation decisions. Part D includes a single cohort (open-label, single-sequence design with 8 subjects) to evaluate the safety, tolerability, PK, and PD of a single dose of TLC-1180 in a tablet formulation under fasted, then fed conditions. The results of this study will be used to refine dosing strategies for future studies. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic, Pharmacodynamic |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | TLC-1180 |
| Primary outcome measure | 1. Incidence of TLC-1180 treatment-emergent adverse events: Adverse events (AEs) - severity of the AEs will be graded using the Common Terminology Criteria for AE (CTCAE) (v5.0). The relationship between AEs and the study drug will be indicated as related or not related. [Time Frame: Through study completion: Day 15 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study] 2. PK of TLC-1180 AUC: Area under the concentration-time curve [Time Frame: Through study completion: Day 15 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study] 3. PK of TLC-1180 Cmax: Maximum plasma concentration [Time Frame: Through study completion: Day 15 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study] 4. PK of TLC-1180 tmax: Time to reach Cmax [Time Frame: Through study completion: Day 15 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study] 5. PK of TLC-1180 t1/2: Half-life [Time Frame: Through study completion: Day 15 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study] 6. PK of TLC-1180 CL/F: Apparent clearance, calculated as dose/AUC0-inf [Time Frame: Through study completion: Day 15 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study] |
| Secondary outcome measures | There are no secondary outcome measures |
| Overall study start date | 01/09/2025 |
| Completion date | 01/11/2026 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 55 Years |
| Sex | All |
| Target number of participants | 288 |
| Key inclusion criteria | 1. Non-smoking, healthy male or female subject between 18 and 55 years of age, inclusive 2. Body mass index from 19 to 35 kg/m2, inclusive 3. Estimated glomerular filtration rate ≥ 80 mL/min 4. Normal liver biochemistry tests 5. Screening laboratory evaluations (hematology, chemistry, and urinalysis) must fall within the normal range of the local laboratory's reference ranges unless the results have been determined by the investigator to have no clinical significance 6. Subject must have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant by the investigator 7. Females of childbearing potential must have a negative pregnancy test at Screening and clinic admission 8. Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception 9. Must, in the opinion of the investigator, be in good health based upon medical history and physical examination, including vital signs |
| Key exclusion criteria | 1. Pregnant or lactating subjects 2. Subjects who have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with the subject's treatment, assessment, or compliance with the protocol 3. Subjects who have received any investigational compound within 30 days or 5 half-lives, whichever is longer, prior to study drug dosing 4. Current alcohol abuse that is judged by the investigator to potentially interfere with the subject's compliance or safety 5. Current substance abuse that is judged by the investigator to potentially interfere with the subject's compliance or safety 6. A positive test result for human immunodeficiency virus (HIV-1) antibody, hepatitis B (HBV) surface antigen, or hepatitis C (HCV) antibody 7. Subjects who have taken any prescription medications or over-the-counter medications, including herbal products, within 28 days prior to start of study drug dosing, with the exception of vitamins, acetaminophen (paracetamol), ibuprofen, and/or hormonal contraceptive medications 8. Subjects who have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to Screening or expected to receive these agents during the study (e.g., corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) 9. Medical history of serious skin disease in the opinion of the investigator, such as but not limited to rash, food allergy, eczema, psoriasis, or urticaria 10. Medical history of drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity) 11. Presence or history of cardiovascular disease, including significant cardiovascular disease (including a history of myocardial infarction based on ECG and/or clinical history), history of cardiac conduction abnormalities (including any history of ventricular tachycardia), congestive heart failure, cardiomyopathy with left ventricular ejection fraction < 40%, a family history of Long QT Syndrome, or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years 12. Syncope, palpitations, or unexplained dizziness 13. Implanted defibrillator or pacemaker 14. Medical history of liver disease, including but not limited to alcoholic liver disease, autoimmune disorders (e.g., primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency) 15. History of rhabdomyolysis 16. Severe peptic ulcer disease, gastroesophageal reflux disease, or other gastric acid hypersecretory conditions 17. History of medical or surgical treatment that permanently alters intestinal absorption (e.g., gastric or intestinal surgery) 18. Subjects who have received vaccination for COVID-19 within 14 days of Admission |
| Date of first enrolment | 20/10/2025 |
| Date of final enrolment | 01/01/2026 |
Locations
Countries of recruitment
- New Zealand
Study participating centre
OrsoBio Research Site
Auckland
1010
New Zealand
1010
New Zealand
Sponsor information
OrsoBio, Inc.
Industry
Industry
101 Jefferson Drive
Menlo Park
94025
United States of America
| Phone | +1 650-382-2225 |
|---|---|
| Clinicaltrials_Inquires@orsobio.com | |
| Website | https://orsobio.com/ |
Funders
Funder type
Industry
OrsoBio, Inc.
No information available
Results and Publications
| Intention to publish date | 01/11/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | 1. Peer-reviewed scientific journal 2. Internal report 3. Conference presentation 4. Publication on website 5. Submission to regulatory authorities |
| IPD sharing plan | The datasets generated during and/or analyzed during the current study are not expected to be made available due to confidentiality reasons. |
Editorial Notes
20/10/2025: Internal review.
16/10/2025: Study's existence confirmed by the Northern A Health and Disability Ethics Committee (HDEC), Ministry of Health, New Zealand.
