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

NCT05795517 | Completed Phase 2

• 1 other identifier: HSK31679-201
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

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).

Conditions

Hypercholesterolemia

Keywords

hypercholesterolemia; non-alcoholic fatty liver disease(NAFLD); THR-β

Outcome Measures

Primary Outcomes (2)

• Percentage change in LDL-C from baseline at 12 week;

  Percentage change in fasting low-density lipoprotein cholesterol (LDL-C) from baseline after 12 weeks of treatment;

  Baseline and Week 12

• Percentage change in MRI-PDFF from baseline at 12 week；

  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;

  Baseline and Week 12

Secondary Outcomes (9)

• Percentage change in fasting LDL-C from baseline;

  Week2,4,8

• The proportion of patients with MRI-PDFF decreased by > 30%

  Baseline and Week 12

• Proportion of patients with LDL-C<3.34mmol/L（<130mg/dL）

  Baseline and Week 12

• Percentage change of fasting TG from baseline;

  Week2,4,8,12

• Percentage change of fasting TC from baseline;

  Week2,4,8,12

Study Arms (5)

HSK31679 low dose

EXPERIMENTAL

Drug: HSK31679 low dose

HSK31679 medium dose

EXPERIMENTAL

Drug: HSK31679 medium dose

HSK31679 high dose

EXPERIMENTAL

Drug: HSK31679 high dose

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Ezetimibe

ACTIVE COMPARATOR

Drug: Ezetimibe 10mg

Interventions

HSK31679 low dose DRUG

HSK31679 low dose and placebo of HSK31679 ，QD，oral，Day1 to week 12

HSK31679 low dose

HSK31679 medium dose DRUG

HSK31679 medium dose and placebo of HSK31679 ，QD，oral，Day1 to week 12

HSK31679 medium dose

HSK31679 high dose DRUG

HSK31679 high dose and placebo of HSK31679 ，QD，oral，Day1 to week 12

HSK31679 high dose

Placebo DRUG

placebo ，QD，oral，Day1 to week 12

Placebo

Ezetimibe 10mg DRUG

Ezetimibe 10mg+placebo of HSK31679 ，QD，oral，Day1 to week 12

Ezetimibe

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Haisco Pharmaceutical Group Co., Ltd.: lead

Study Sites (1)

Beijing Tsinghua Changgung Hospital, Tsinghua University

Beijing, China

Location

Related Publications (1)

• Xue F, Ma W, Gao J, Chen J, Yue W, Bu P, Chen Q, Chen H, Sheng J, Chen L, Liu F, Li G, Zhu C, Zhong B, Zhang J, Cai Q, Wang L, Chen Y, Pei Z, Yao L, Lv L, Gao Y, Xia B, Ji X, Liu Y, Du L, Ma G, Hao K, Li F, Wu T, Huo Y, Wei L. Efficacy and Safety of HSK31679 in Asian Patients With MASLD: A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2025 Aug 20:S1542-3565(25)00703-7. doi: 10.1016/j.cgh.2025.08.009. Online ahead of print.

  PMID: 40846146 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia; Non-alcoholic Fatty Liver Disease

Interventions

Ezetimibe

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2023
• First Posted: April 3, 2023
• Study Start: April 26, 2023
• Primary Completion: February 20, 2024
• Study Completion: March 1, 2024
• Last Updated: April 9, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)