A Phase 1, Double-blind, Randomized Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Single Dose and Multiple Doses of CG-0416 in Healthy Participants.

Overview

A Phase 1, double-blind, randomized study to evaluate the safety, tolerability, pharmacodynamics, and pharmacokinetics of single dose and multiple doses of CG-0416 in healthy participants. HongKong Curegene Innovation Co. Limited is developing the study drug CG-0416 as a potential new treatment for overweight and obesity. The purpose of this research is to investigate the safety, tolerability (if any side effects occur), pharmacokinetics (the amount of study drug or any of its breakdown products in your body) and pharmacodynamics (how the study drug affects your body), of single and multiple oral doses of a study drug called CG-0416.

Interventions

• Drug CG-0416
  CG-0416 is a novel selective, liver-directed thyroid hormone receptor beta (THR-β) agonist, given orally once daily.

Primary outcome measures

• To determine number of participants with treatment-related adverse events as assessed by CTCAE v6.0 of single dose and multiple doses of CG-0416 in healthy participants. [Time frame: up to 3 weeks]
• To determine the safety and tolerability of single dose and multiple doses of CG-0416 in healthy participants [Time frame: up to 3 weeks]
• To determine the safety and tolerability of single dose and multiple doses of CG-0416 in healthy participants. [Time frame: up to 3 weeks]

Secondary outcome measures (8)

• To define pharmacokinetics (PK) profile of CG-0416 and its active metabolite CG-0400 [Time frame: up to 3 weeks]
• To define pharmacokinetics (PK) profile of CG-0416 and its active metabolite CG-0400 [Time frame: up to 3 weeks]
• To define pharmacokinetics (PK) profile of CG-0416 and its active metabolite CG-0400 [Time frame: up to 3 weeks]
• To define pharmacokinetics (PK) profile of CG-0416 and its active metabolite CG-0400 [Time frame: up to 3 weeks]
• To define pharmacokinetics (PK) profile of CG-0416 and its active metabolite CG-0400 [Time frame: Up to 3 weeks]
• To assess pharmacodynamic (PD) parameters [Time frame: up to 3 weeks]
• To assess pharmacodynamic (PD) parameter insulin [Time frame: up to 3 weeks]
• To assess pharmacodynamic (PD) parameter sex hormone binding globulin (SHBG) [Time frame: up to 3 weeks]

Eligibility criteria

Inclusion criteria

• Male and female participants aged 18 to 60 years, inclusive, at the time of screening.
• BMI of ≥ 18 kg/m2 to ≤ 32 kg/m2 for SAD and ≥ 21 kg/m2 to ≤ 35 kg/m2 for MAD at screening, and body weight > 50 kg for SAD and MAD.
• Participants will be assessed to be in good health by the investigator, such as no clinically relevant abnormalities that will affect participant safety in the opinion of the investigator based on medical history, physical examination, clinical laboratory assessments (hematology, serum chemistry, coagulation, urinalysis, TH), and 12-lead ECG.
• LDL-C > 1.8 mmol/L (70 mg/dL) in SAD, LDL-C > 2.6 mmol/L (100 mg/dL) in MAD.
• Self-reported stable weight (within ± 5% change) for at least 3 months prior to screening.
• Participant and his/her sexual partner are not planning to fall pregnant and male participants can't donate sperm for 95 days after the last dose of study drug and willing to use two or more effective contraception methods (contraception guidance is provided in Appendix 17.1). Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug and must not be breastfeeding, lactating or planning pregnancy during the study period. WOCBP are defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral salpingectomy or bilateral oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in the absence of other biological causes. In addition, females under the age of 55 years must have a documented serum FSH level > 40 mIU/mL to confirm menopause. Male participants with potentially postmenopausal partners who are under the age of 55 years must use condoms unless their partner's postmenopausal status has been confirmed by FSH level.
• Participants have a full understanding of the trial content, process and possible adverse reactions, and voluntarily signed the informed consent form (ICF).

Exclusion criteria

• Clinically significant infection and/or cardiovascular, hematologic, renal, hepatic, pulmonary, endocrine, gastrointestinal, immunologic, dermatologic, neurologic, current or history of ADHD, anxiety or depression, or psychiatric disease at screening that, or its treatment, may have interfered with the conduct of the study (e.g., study procedure compliance, safety assessment, study results interpretation) or, in the judgment of the investigator, will have placed the participant at an unacceptable risk if participating in the study.
• Clinically significant diseases (including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrine, neoplastic, pulmonary, immunological, psychiatric or cardiovascular disease) within 6 months before screening.
• Thyroid diseases: a) active hyperthyroidism; b) TSH >7 IU/L with symptoms of hypothyroidism or >10 IU/L without symptoms.
• Diagnosis of type 1 or 2 diabetes or other autoimmune diabetes (fully resolved gestational diabetes will be permitted).
• Glycated hemoglobin (HbA1c) > 6.5% or fasting blood glucose ≥ 7.0 mmol/L.
• Fasting (TG ≥ 500 mg/dL (or 5.65 mmol/L) at screening.
• Participant meets any of the following:

• Transaminases (AST, ALT) > 1.5 × ULN.
• Alkaline phosphatase (ALP) > 1.5 × ULN.
• Serum total bilirubin > 1.5 × ULN (participants diagnosed with Gilbert's syndrome at screening are allowed to meet all other criteria).
• Platelet count < 100,000/mm³.
• International normalized ratio (INR) > ULN (as per the local laboratory reference range).
• Albumin < 35 g/L.
• Estimated glomerular filtration rate < 60 mL/min/1.73m2 per Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 formula.
• Severe allergic diseases or suspected allergy to any component of the study drug, allergic constitution (multiple drug and food allergy) judged by the investigator.
• Any of the following abnormalities on the 12-lead ECG at screening:

• QTcF (Fridericia-corrected QT interval) > 450 msec for males or > 470 msec for females.
• In addition to the above, any clinically significant ECG abnormality, as judged by the investigator.
• Systolic blood pressure > 145 mmHg and diastolic blood pressure > 95 mmHg in supine position (at least 5 minutes) at screening, confirmed by retest.
• Use of antibiotics or immunosuppressive drugs (e.g., systemic corticosteroids) within 30 days prior to administration of CG-0416 on Day 1.
• Any short-term or long-term treatment for obesity within 3 months prior to screening.
• For use of prescription medication, within 14 days or 5 half-lives (whichever is longer) before screening with the exception of hormone replacement and contraception therapy. For use of over-the-counter (OTC) medications, food supplements (excluding routing vitamins, paracetamol, ibuprofen), weight loss and fat reduction supplements (L-carnitine, green coffee extract, chitosan, weight loss tea, yerba mate tea, meal replacement, etc.), supplements for thyroid endocrine disruption (iodine supplements, seaweed and kelp extracts, etc.), lipid-lowering supplements (fish oil, etc.) etc. 7 days before screening is sufficient (Only vitamins and other supplements that do not affect the study drug are allowed to be used. Other supplements are not permitted).
• Smoking > 5 cigarettes (or equivalent amount of nicotine products) per week within 30 days before the screening or inability to abstain from tobacco products during the study.
• Any vaccination within 14 days prior to screening or anticipated administration of a live vaccine during the study.
• Receipt of an investigational drug or device or participation in a drug study within 60 days (or 5 half-lives of the drug, whichever is longer) before dosing on Day 1.
• Positive during screening for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C antibody (amplification test to confirm if positive; cured hepatitis C can be enrolled), or human immunodeficiency virus (HIV) antibody, treponema pallidum antibody.
• History of drug abuse within 6 months before screening, or positive drug abuse test at screening.
• Weekly alcohol consumption of more than 10 units of alcohol (1 unit of alcohol = 360 mL of beer or 45 mL of spirit with the alcohol content of 40% or 150 mL of wine) in any week within the past 3 months before screening; intake of alcohol-containing products within 48 hours prior to the first dose of study drug or inability to abstain from any alcohol during the study, or positive alcohol test at screening.
• Donation of more than 400 mL of blood or plasma within 30 days before screening or planned donation within 90 days of study treatment administration.
• Consumption/consumption of coffee, tea, grapefruit, chocolate or soft drinks such as cola containing methylxanthines (theophylline, caffeine or theobromine) within 48 hours before dosing.
• Strenuous exercise, such as weightlifting, sprinting, long-distance running, cycling, swimming, and playing soccer, is performed within 72 hours before screening and any study visit until the follow-up has been completed; if it is not within the window period before the above-mentioned screening and study visits, maintenance of daily exercise or activity plan is allowed.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Sequential

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Australia · 1 center

• Nucleus Network Pty Ltd. — Melbourne

Identifiers

NCT: NCT07724431 · CG-AU-0416-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗