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

Haisco Pharmaceutical Group

Status and phase: Completed; Phase 2

Conditions: Hypercholesterolemia

Treatments: Drug: Placebo; Drug: HSK31679 high dose; Drug: Ezetimibe 10mg; Drug: HSK31679 medium dose; Drug: HSK31679 low dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT05795517

HSK31679-201

Details and patient eligibility

About

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).

Enrollment: 210 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Must be willing to participate in the study and provide written informed consent.
2. Male or female aged 18 ≤ age < 65 at the time of signing the informed consent.
3. 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）.
4. (BMI) ≥18kg/m2 and female subjects ≥45.0 kg and male subjects ≥50.0 kg.
5. During screening, fasting triglyceride (TG) <5.65 mmol/L.
6. During screening,MRI-PDFF≥8%.
7. Weight changes≤5% in the 4 weeks prior to screening.

Exclusion criteria

1. 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.

2. Homozygous familial hypercholesterolemia (HoFH) was diagnosed by genetic or clinical criteria.

3. 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

4. Before screening, LDL-C plasma exchange was performed within 12 months.

5. In the past, PCSK9 inhibitors, Lomitapide and Mipomersen were used for treatment.

6. uncontrolled hypertension had systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100mmHg at screening/baseline.

7. 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.

8. 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.

9. 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.

10. Chronic systemic disease or history, including but not limited to

    1. Have a serious cardiopulmonary disease or history,Neurological disease or history,Autoimmune disease,Chronic digestive disease or history
    2. 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))
    3. 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
    4. Disease or medical history assessed by the investigator as likely to affect the study

11. Bariatric surgery within 12 months at the time of screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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210 participants in 5 patient groups, including a placebo group

HSK31679 low dose

Experimental group

Treatment:

Drug: HSK31679 low dose

HSK31679 medium dose

Experimental group

Treatment:

Drug: HSK31679 medium dose

HSK31679 high dose

Experimental group

Treatment:

Drug: HSK31679 high dose

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

Ezetimibe

Active Comparator group

Treatment:

Drug: Ezetimibe 10mg