A Clinical Study Evaluating the Safety, Tolerability, and Efficacy of MT1013 in Hemodialysis Subjects With Secondary Hyperparathyroidism

A Double-blind, Randomized, Placebo-controlled, Single-dose Escalation and Multi-dose Escalation Clinical Study Evaluating the Safety, Tolerability, and Efficacy of MT1013 in Hemodialysis Subjects With Secondary Hyperparathyroidism, Along With a Single-arm Study Assessing the Long-term Efficacy and Safety of MT1013

A multicenter, Phase II, randomized, double-blind, single ascending dose (SAD) and multiple ascending dose (MAD), as well as single-arm clinical study evaluating the long-term efficacy and safety of MT1013 in hemodialysis subjects with secondary hyperparathyroidism. The SAD study consists of five cohorts at doses of 5, 10, 20, 40, and 60 mg. The MAD study consists of three cohorts at doses of 5, 10, and 20 mg. In both the SAD and MAD studies, each cohort includes 8 subjects (6 subjects receive the active investigational drug, and 2 subjects receive matching placebo), and the cohorts are conducted sequentially. In the long-term dosing cohort, all subjects will undergo regular hemodialysis three times per week, receiving the drug once after each hemodialysis session for a total duration of 52 weeks

Inclusion Criteria (Subjects must meet all of the following criteria to participate in the trial):

1. Male or non- pregnant, non-lactating female aged 18 to 80;
2. The patient has been on stable, adequate hemodialysis treatment for >3 months prior to screening;
3. Intact parathyroid hormone (iPTH) level of at least 300 pg/mL;
4. Serum calcium (corrected serum calcium if albumin <40 g/L) ≥2.25 mmol/L (9.0mg/dL);
5. Hemoglobin ≥ 8.0 g/dL;
6. Subject is clinically stable, as judged by medical history, physical examination, and routine laboratory tests, apart from chronic renal failure;
7. Able to understand and willing to sign the written informed consent form;
8. Women of childbearing potential must have a negative pregnancy test result prior to enrollment, or be postmenopausal for at least 1 year, or be permanently sterile(i.e., documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) for ≥6 weeks. Fertile men with partners of childbearing potential and women of childbearing potential must use effective contraception (i.e., any combination of two of the following: male or female condom with spermicidal gel,diaphragm, sponge, or cervical cap with spermicidal gel) from signing the informed consent until 90 days after MT1013 infusion.

Postmenopausal is defined as:

Age ≥55 years & amenorrhea for ≥12 months;

Or Age <55 years but no spontaneous menses for at least 2 years;

Or Age <55 years with spontaneous menses within the past 1 year, but currently amenorrheic, and with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels >40 IU/L) or postmenopausal estradiol levels (<5.3 pmol/L or 5 ng/dL) or meeting the laboratory's definition of "postmenopausal range";Having undergone bilateral oophorectomy.

Exclusion Criteria (Subjects meeting any of the following criteria will be excluded from the study):

1 .History of severe ventricular arrhythmia or symptomatic ventricular arrhythmia at screening, or QTc >470 ms for males or >480 ms for females at screening;

2. Subjects with heart failure symptoms，class III or IV by New York Heart Association (NYHA) ， at screening;

3. History of myocardial infarction, coronary angioplasty, or coronary artery bypass graft within the past 6 months;

4. History of seizures or having received treatment for seizures;

5. Prior parathyroidectomy;

6. Serum transaminases (alanine aminotransferase, aspartate aminotransferase) >3 times the upper limit of normal at screening; or serum albumin <30 g/L;

7.History of organ transplant (excluding being on the kidney transplant waiting list), hematopoietic stem cell transplant, or bone marrow transplant; or patients planning to undergo organ transplantation;

8.Severe uncontrolled hypertension, defined as systolic blood pressure >180 mmHg and diastolic blood pressure >100 mmHg despite optimal medical therapy before enrollment;

9.Known malignancy or other comorbidities with a life expectancy of <3 months (except for patients disease-free for ≥5 years, or disease-free for ≥5 years after the last dose of chemotherapy );

10.Known alcohol or illicit drug abuse within 12 months prior to screening, unwillingness or inability to abstain from alcohol for 24 hours prior to each study visit, or unwillingness or inability to limit alcohol consumption to a maximum of 2 drinks per day during the study (one drink is equivalent to 360 mL of regular beer, 150 mL of wine, or 45 mL of 40% alcohol spirits);

11.Positive for human immunodeficiency virus (HIV) or known diagnosis of acquired immunodeficiency syndrome (AIDS) at screening;

12.Subjects positive for hepatitis B surface antigen (HBsAg) at screening (indicative of chronic hepatitis B) AND with serum transaminases (alanine aminotransferase, aspartate aminotransferase) >2 times the upper limit of normal;

13.Positive for hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR) at screening (indicative of active hepatitis C - usually screened via hepatitis C antibody [HCV-Ab], with PCR for HCV RNA if HCV-Ab positive);

14.Patients with known hypersensitivity to the investigational product and/or its components;

15.Patients who have participated in another clinical trial and received an investigational drug within 8 weeks prior to the first dose or within 5 half-lives of the investigational drug (whichever is longer);

16. Patients who have previously received MT1013;

17. Subjects who have received cinacalcet treatment within 8 days prior to the first dose;

18. Pregnant or potentially pregnant women or lactating women;

19. Inability to fully comply with the study protocol;

20.Any other medical or psychiatric condition that, in the investigator's opinion, precludes participation in the study;

21. Subjects with active gastrointestinal bleeding or a high risk of astrointestinal bleeding tendency at screening.