Clinical trial NCT06541457: A Study on Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HRS-7249 Injection in Healthy Subjects
Official title: To Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Subcutaneous Injection of HRS-7249 in Healthy Subjects - a Randomized, Double-blind, Dose-increasing, Placebo-controlled Phase I Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hyperlipidemia
Lead sponsor: Fujian Shengdi Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-08-07
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: It is a randomized, double-blind, single-dose, placebo-controlled phase I clinical trial. The study plans to conduct four to six dose groups of dose 1, dose 2, dose 3, dose4, dose5 (optional), and dose 6(optional). Eight subjects will be enrolled for each dose group, with six administered HRS-7249 injection and two administered placebo. A total of 32 to 48 healthy subjects are planned to be enrolled.


Eligibility criteria: Inclusion Criteria:

1. Able and willing to provide a written informed consent；
2. Age ≥ 18 and ≤ 65 years old on the day of signing the informed consent ；
3. 0.9 mmol/L≤TG≤5.6 mmol/L；
4. Male or female；
5. Male subjects weigh ≥ 50 kg and \< 90 kg , female subjects weigh ≥ 45kg and \< 90 kg, and BMI is in the range of 19\~30 kg/m2 ；(including boundary values) Normal or abnormality such as vital signs, physical examination and laboratory examination have no clinical significance；
6. Subjects must be willing to use a highly effective method of contraception as deemed appropriate by the investigator throughout the study and for at least 6 months after the last study drug administration.

Exclusion Criteria:

1. Those who suffer from any disease that affects drug absorption, distribution, metabolism, and excretion, or can reduce compliance determined by investigators;
2. Those who suffer from any clinical diseases such as as cardiovascular, liver, kidney, digestive tract, psychiatric, hematological, metabolic abnormalities;
3. A clinically significant history of drug allergies or atopic allergic diseases (asthma, urticaria, eczematous dermatitis);
4. Those with a history of malignant diseases;
5. Those with a history of involving clinical trials of any other drugs or medical devices within the previous 3 months of screening or planned to be conducted during the study period (excluding screening failures), or those who are still within 5 half-lives of the drugs before screening (whichever is longer);
6. Those who have experienced severe trauma or surgery within the previous 6 months, or plan to undergo surgery during the trial period; Serious infected individuals within the previous 3 months of screening;
7. Those who have used any drugs during the screening period or within 2 weeks before the baseline period; or those who are still in 5 half-lives of the drug at the time of screening (whichever is longer);
8. Serum LDL-C ≥ 4.1mmol/L;
9. Platelet count\<100 × 109/L;
10. Creatinine≥ upper limit of normal (ULN);
11. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma glutamyltransferase (GGT) ≥2×ULN, or total bilirubin ≥1.5×ULN;
12. During the screening period, human immunodeficiency virus antibodies (HIV-Ab), syphilis serological tests, hepatitis B virus surface antigen (HBs-Ag), or hepatitis C virus antibodies (HCV Ab) is positive;
13. Creatine kinase (CK) ≥ 3 ×ULN;
14. Thyroid stimulating hormone (TSH)\< limit of normal (LLN) or≥ 1.5 ×ULN;
15. Glomerular filtration rate (eGFR)\<60 mL/min/1.73m2;
16. Urine drug screening positive;
17. Those with a history of blood donation within the previous three months, severe blood loss (blood loss ≥ 400 mL), or who have received a blood transfusion within four weeks;
18. Those who have received the vaccine within the previous two weeks or plan to receive it during the trial process;
19. Those who started new physical exercise or made significantly changed their previous exercise activities within the previous 4 weeks, or who were unable to maintain basic stability in exercise during the study period;
20. Those who have made significant adjustments to their previous diet within the previous 4 weeks, or those whose diet cannot maintain basic stability during the study period;
21. Those who smoke an average of 5 or more cigarettes per day within the previous 4 weeks;
22. In the four weeks before screening, women's daily alcohol intake was more than 15 g, men's more than 25 g and more than twice a week, or the screening period and baseline period alcohol breath test (alcohol blood test can be replaced) was positive;
23. Those with a history of drug use or abuse;
24. Researchers, assistant researchers, research assistants, pharmacists, research coordinators, or other directly involved protocol implementers;
25. The researchers believe that subjects with any unfavorable factors to participate in this experiment.

Primary outcomes:
measure: Safety and tolerability: Incidence of subjects with adverse events (AEs)
timeFrame: Baseline up to Day 169
Secondary outcomes:
measure: Pharmacokinetics (PK) parameter: AUC0-t for HRS-7249
timeFrame: Baseline up to 48 hours after dosing
measure: Pharmacokinetics (PK) parameter: AUC0-∞ for HRS-7249
timeFrame: Baseline up to 48 hours after dosing
measure: Pharmacokinetics (PK) parameter: Cmax for HRS-7249
timeFrame: Baseline up to 48 hours after dosing
measure: Pharmacokinetics (PK) parameter: Tmax for HRS-7249
timeFrame: Baseline up to 48 hours after dosing
measure: Pharmacokinetics (PK) parameter: t1/2 for HRS-7249
timeFrame: Baseline up to 48 hours after dosing
measure: Pharmacokinetics (PK) parameter: CL/F of HRS-7249 for administration subcutaneously
timeFrame: Baseline up to 48 hours after dosing
measure: Pharmacokinetics (PK) parameter: V/F of HRS-7249 for administration subcutaneously
timeFrame: Baseline up to 48 hours after dosing
measure: Pharmacodynamics (PD): TG
timeFrame: Baseline up to Day 169
measure: Pharmacodynamics (PD): HDL-C
timeFrame: Baseline up to Day 169
measure: Pharmacodynamics (PD): LDL-C
timeFrame: Baseline up to Day 169
measure: Pharmacodynamics (PD): non-HDL-C
timeFrame: Baseline up to Day 169
measure: Pharmacodynamics (PD): VLDL-C
timeFrame: Baseline up to Day 169
measure: Pharmacodynamics (PD): TC
timeFrame: Baseline up to Day 169
measure: Pharmacodynamics (PD): Lp(a)
timeFrame: Baseline up to Day 169
measure: Pharmacodynamics (PD): ApoB
timeFrame: Baseline up to Day 169
measure: Pharmacodynamics (PD): ApoA1
timeFrame: Baseline up to Day 169
measure: Immunogenicity: Proportion of anti-drug antibodies (ADA) positive subjects
timeFrame: Baseline up to Day 169
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: