Clinical Study of TJ0113 Capsule in the Treatment of Patients With Sarcopenia

A Randomized, Double-Blind, Multicenter, Placebo Parallel-Controlled Phase II Clinical Study to Evaluate the Efficacy and Safety of TJ0113 Capsule in the Treatment of Patients With Sarcopenia

This study is a randomized, double-blind, multicenter, placebo parallel-controlled Phase II clinical study designed to evaluate the clinical efficacy and safety of TJ0113 Capsule in patients with sarcopenia. The entire study plans to enroll 204 participants with sarcopenia. Eligible participants will be stratified by age (< 70 years or ≥ 70 years to ≤ 80 years or > 80 years) and block-randomized in a 1:1:1:1 ratio into 4 groups (TJ0113 Capsule 100 mg dose group; TJ0113 Capsule 200 mg dose group; TJ0113 Capsule 400 mg dose group; placebo group), with 51 participants per group. Participants in the placebo group will then be re-randomized in a 1:1:1 ratio to the respective dose groups (100 mg, 200 mg, and 400 mg). After randomization, study participants will receive continuous oral administration for 26 weeks with efficacy and safety evaluations, followed by a 1-week follow-up period after the end of treatment.

Inclusion Criteria:

1. Voluntarily participate in the clinical study and sign the informed consent form (ICF), willing and able to comply with the study protocol (e.g., able to understand and complete questionnaires, adhere to visit schedules, and use study medication);

2. Male or female aged ≥60 years at the time of signing the ICF;

3. Meet the diagnostic criteria of the "Guideline for Diagnosis and Treatment of Sarcopenia in China (2024 Edition)", specifically as follows:

   3.1Low muscle mass: DXA measurement of muscle mass < 7.0 kg/m2 in males / < 5.4 kg/m2 in females, or BIA measurement of muscle mass < 7.0 kg/m2 in males / < 5.7 kg/m2 in females; 3.2Low muscle strength (grip strength < 28.0 kg in males, grip strength < 18.0 kg in females); and/or physical dysfunction (walking speed in free state < 1 m/s, or 5 Times Sit-to-Stand Test ≥ 12 s, or Short Physical Performance Battery score ≤ 9).

4. Able to complete the 400-meter Walk Test within 15 minutes without sitting down, leaning against a wall, requiring assistance from others, or using a walker or cane.

5. Participants of childbearing potential (including spouses of male participants) must have no plans for pregnancy or sperm donation from the screening period until 6 months after the last dose, and must be willing to use at least one effective contraceptive method (see Appendix 1) for contraception.

6. Individuals whose results from comprehensive physical examination, vital signs, routine laboratory tests (complete blood count, blood biochemistry, urinalysis, coagulation), 12-lead electrocardiogram, chest X-ray, etc., are normal, or although abnormal, are determined by the investigator to be in the following condition: conditions considered stable and controlled by the investigator,planned during the studypatients with chronic diseases (e.g., hypertension and hyperlipidemia controlled within normal range, well-controlled non-insulin-dependent diabetes, etc.) who are taking medication regularly according to the established regimen and whose condition does not affect the study observation indicators after enrollment; abnormal items in screening tests determined by the investigator to be related to the patient's age or the aforementioned chronic diseases.

Exclusion Criteria:

1. Any medical condition that may interfere with adequate participation in the trial, including but not limited to the following: a history of epilepsy or complications, a history of hemolytic anemia, pulmonary embolism, or malignant tumors, or a positive tumor marker test result during the screening period that is assessed by the investigator as clinically significant;
2. New York Heart Association (NYHA) Class III or above congestive heart failure, unstable angina pectoris, acute myocardial infarction, hemorrhagic stroke, ischemic stroke (including transient ischemic attack) occurring within 6 months prior to screening; or Within 6 months prior to screening, undergone percutaneous coronary intervention, coronary artery bypass grafting, or cardiac valve repair/replacement; or at the time of screening, the presence of ventricular tachycardia, ventricular fibrillation, polymorphic ventricular tachycardia, etc., as judged by the investigator that may be life-threatening or lead to hemodynamic instability arrhythmia;
3. Personal or family history of long QT syndrome, family history of sudden death before the age of 40 in first-degree relatives (parents, children, and siblings); and/or personal history of unexplained syncope within 1 year prior to screening; and/or based on resting ECG results at screening: QT interval corrected for heart rate using Fridericia's formula, QTcF > 450 ms (males), QTcF > 470 ms (females) [Fridericia's formula: QTc = QT/(RR0.33), where RR represents the standard heart rate value, calculated as 60 divided by heart rate];
4. Presence of uncontrolled hypertension at screening, defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg (confirmed before randomization);
5. During screening chest pain, severe dyspnea, or other safety issues occurring during functional testing (e.g., 400-meter walk test), as assessed by the investigator to be unsuitable for participation in this study;
6. Presence of clinically significant hepatic impairment, defined as total bilirubin (TBIL) >2× upper limit of normal (ULN) and/or alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2× ULN;
7. Presence of clinically significant renal impairment (creatinine clearance rate [Ccr] <30 mL/min). The formula for calculating Ccr is provided in Appendix II;
8. Suffering from underlying diseases that may cause malnutrition, including chronic diarrhea (defined as a significant increase in bowel movement frequency compared to usual habits [>3 times/day], lasting >4 weeks, or recurrent diarrhea with intervals of 2-4 weeks), Crohn's disease and other digestive system diseases, neuropsychiatric disorders such as anorexia nervosa, uncontrolled diabetes mellitus (fasting blood glucose >8.3 mmol/L after treatment) and other metabolic diseases, chronic obstructive pulmonary disease (Modified Medical Research Council Dyspnea Scale [MMRC] score ≥2), chronic heart failure (diagnosed according to the Chinese Guidelines for the Diagnosis and Treatment of Heart Failure, 2024, NYHA class III or above), and other chronic wasting diseases, which, in the investigator's judgment, make the patient unsuitable for participation in this study;
9. Individuals with neuromuscular diseases (e.g., Parkinson's disease), or other muscle system disorders such as muscular atrophy or myositis that could affect the diagnostic parameters of sarcopenia;
10. Patients with implanted cardiac pacemakers or stents who, upon investigator assessment, are deemed unsuitable for participation in this study (Note: BIA testing is not recommended for individuals with implanted electronic devices such as cardiac pacemakers);
11. Individuals with physical disabilities or injuries/surgeries to the upper or lower limbswithin 3 months prior to screeningthat may affect grip strength or gait speed measurements;
12. Participants with a history of severe allergy, or known hypersensitivity/allergic reaction or intolerance to any component of the investigational product;
13. Use of drugs affecting bone and muscle metabolism (bisphosphonates, estrogens, calcitonin, teriparatide, long-term oral or injectable corticosteroids [use for ≥2 weeks or requiring long-term use as determined by the investigator]) within 7 days or 5 half-lives prior to screening, whichever is longer (Note: Patients who have received a stable dose of denosumab for ≥6 months prior to screening and do not intend to change the dose during the study are permitted for enrollment; patients who plan to receive stable doses of bone mineralization promoters such as calcium, vitamin D, active vitamin D and its analogs [including calcitriol, alfacalcidol, etc.] within 4 weeks prior to the first dose and during the study period are permitted for enrollment);
14. Evidence of alcohol abuse (average weekly consumption of ≥14 units of alcohol, where 1 unit ≈ 360 mL of beer, or 45 mL of liquor, or 150 mL of wine) or alcohol dependence within 6 months before screening, which in the investigator's opinion would interfere with the participant's understanding or completion of the study;
15. Patients with a history of drug dependence/substance abuse within the past 1 year prior to screening;
16. Positive for hepatitis B surface antigen (HBsAg) with HBV-DNA ≥ 1000 copies/mL or 200 IU/mL, or positive for hepatitis C virus (HCV) antibody with HCV RNA ≥ the lower limit of detection of the study site, or positive for human immunodeficiency virus (HIV) antibody, or positive for Treponema pallidum antibody at screening;
17. Participation in a clinical study involving administration of an investigational drug, device, or surgery within 3 months or 5 half-lives (whichever is longer) before the first dose;
18. Inability to swallow oral medications, or, in the investigator's judgment, presence of any condition that could significantly affect drug absorption, distribution, metabolism, or excretion (e.g., active enteropathy, partial or complete intestinal obstruction, chronic diarrhea), or any condition that could pose a risk to the participant;
19. Subjects who have a history of organ transplantation (excluding corneal transplantation);
20. Donated blood (including blood products) (including blood products) or experienced blood loss ≥400 mL within 1 month prior to screening, or received a blood transfusion (including blood products);
21. Pregnant or breastfeeding women;
22. Other reasons deemed by the investigator that the participant has poor compliance or is unsuitable for participation in this study.