Study of HSK31679 in Subjects With Hypercholesterolemia With Nonalcoholic Fatty Liver Disease（NAFLD）

Sponsor

Haisco Pharmaceutical Group Co., Ltd. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05795517

Collaborator

(none)

200

Enrollment

Arms

9.8

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy and safety of HSK31679 tablets compared with placebo in reducing low-density lipoprotein cholesterol (LDL-C) and MRI-PDFF after 12 weeks of treatment in patients with hypercholesterolemia and non-alcoholic fatty liver disease (NAFLD).

Condition or Disease	Intervention/Treatment	Phase
Hypercholesterolemia	Drug: HSK31679 low dose Drug: HSK31679 medium dose Drug: HSK31679 high dose Drug: Placebo Drug: Ezetimibe 10mg	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase 2 ,Multicentre, Randomised, Double Blind Double Simulation, Placebo and Positive Controlled Study to Evaluate the Efficacy and Safety of HSK31679 in Patients With Hypercholesterolemia With Non-alcoholic Fatty Liver Disease

Anticipated Study Start Date :

Apr 15, 2023

Anticipated Primary Completion Date :

Dec 26, 2023

Anticipated Study Completion Date :

Feb 8, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HSK31679 low dose	Drug: HSK31679 low dose HSK31679 low dose and placebo of HSK31679 ，QD，oral，Day1 to week 12
Experimental: HSK31679 medium dose	Drug: HSK31679 medium dose HSK31679 medium dose and placebo of HSK31679 ，QD，oral，Day1 to week 12
Experimental: HSK31679 high dose	Drug: HSK31679 high dose HSK31679 high dose and placebo of HSK31679 ，QD，oral，Day1 to week 12
Placebo Comparator: Placebo	Drug: Placebo placebo ，QD，oral，Day1 to week 12
Active Comparator: Ezetimibe	Drug: Ezetimibe 10mg Ezetimibe 10mg+placebo of HSK31679 ，QD，oral，Day1 to week 12

Outcome Measures

Primary Outcome Measures

Percentage change in LDL-C from baseline at 12 week; [Baseline and Week 12]
Percentage change in fasting low-density lipoprotein cholesterol (LDL-C) from baseline after 12 weeks of treatment;
Percentage change in MRI-PDFF from baseline at 12 week； [Baseline and Week 12]
Percentage change of MRI-PDFF(change in liver fat content by nuclear magnetic resonance - Proton Density Fat Fraction) from baseline after 12 weeks of treatment;

Secondary Outcome Measures

Percentage change in fasting LDL-C from baseline; [Week2,4,8]
Percentage change in fasting low-density lipoprotein cholesterol (LDL-C) from baseline after 2, 4, and 8 weeks of treatment;
The proportion of patients with MRI-PDFF decreased by > 30% [Baseline and Week 12]
After 12 weeks of treatment, the proportion of patients with MRI-PDFF decreased by > 30%;
Proportion of patients with LDL-C<3.34mmol/L（<130mg/dL） [Baseline and Week 12]
After 12 weeks of treatment, the proportion of patients with LDL-C<3.34mmol/L（<130mg/dL）
Percentage change of fasting TG from baseline; [Week2,4,8,12]
After 2, 4, 8, 12 weeks of treatment, Percentage change of fasting triglycerides (TG), from baseline;
Percentage change of fasting TC from baseline; [Week2,4,8,12]
After 2, 4, 8, 12 weeks of treatment, Percentage change of fasting total cholesterol (TC) from baseline;
Percentage change of fasting HDL-C from baseline; [Week2,4,8,12]
After 2, 4, 8, 12 weeks of treatment, Percentage change of fasting high-density lipoprotein cholesterol (HDL-C) from baseline;
Percentage change in body weight from baseline [Baseline and Week 12]
Percentage change in body weight from baseline after 12 weeks of treatment.
AUC0-τ of HSK31679 (All subjects) [up to 2,4,7 weeks]
Cmax of HSK31679 (All subjects) [up to 2,4,7 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must be willing to participate in the study and provide written informed consent.
Male or female aged 18 ≤ age < 65 at the time of signing the informed consent.
At the time of screening, patients who had not received lipid-regulation therapy within 6 weeks had fasting LDL-C≥3.34mmol/L（130mg/dL）.
(BMI) ≥18kg/m2 and female subjects ≥45.0 kg and male subjects ≥50.0 kg.
During screening, fasting triglyceride (TG) <5.65 mmol/L.
During screening,MRI-PDFF≥8%.
Weight changes≤5% in the 4 weeks prior to screening.

Exclusion Criteria:

Did not discontinue any lipid-regulating therapy or any drug or supplement that may affect lipid levels 6 weeks before randomization or is expected to do so during the study period.
Homozygous familial hypercholesterolemia (HoFH) was diagnosed by genetic or clinical criteria.
Dyslipidemia caused by other diseases or drugs, such as rheumatoid arthritis, nephrotic syndrome, Cushing's syndrome, hypothyroidism, renal failure, systemic lupus erythematosus, glycogen accumulation, myeloma, lipodystrophy, acute porphyria, polycystic ovarian syndrome, etc
Before screening, LDL-C plasma exchange was performed within 12 months.
In the past, PCSK9 inhibitors, Lomitapide and Mipomersen were used for treatment.
uncontrolled hypertension had systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100mmHg at screening/baseline.
type 1 diabetes, or newly diagnosed type 2 diabetes within 1 month, or poorly controlled type 2 diabetes, or who could not maintain the same hypoglycemic regimen during the study.
Stroke or transient ischemic attack (TIA), acute coronary syndrome, stable angina attack, severe deep vein thrombosis, or pulmonary embolism occurred in the 12 months prior to screening.
Major surgery (including but not limited to: coronary or other revascularization, coronary artery bypass surgery, and transplantation) within 12 months prior to screening or planned during the study period.
Chronic systemic disease or history, including but not limited to
Have a serious cardiopulmonary disease or history,Neurological disease or history,Autoimmune disease,Chronic digestive disease or history
Have thyroid disease or symptomatic abnormalities in thyroid function tests (e.g., thyroid stimulating hormone (TSH) < 1.0 x lower limit of normal (LLN) or > 1.5 x upper limit of normal (ULN))
History of malignancy (excluding cured basal cell carcinoma of the skin, carcinoma in situ, and papillary thyroid carcinoma) or history of antitumor therapy within 5 years prior to screening
Disease or medical history assessed by the investigator as likely to affect the study
Bariatric surgery within 12 months at the time of screening