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

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

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).

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: HSK31679 low dose; Drug: HSK31679 medium dose; Drug: HSK31679 high dose; Drug: Placebo; Drug: Ezetimibe 10mg

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Tsinghua Changgung Hospital, Tsinghua University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: Haisco Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2023
• Primary Completion (Actual): February 20, 2024
• Study Completion (Actual): March 1, 2024

Study Registration Dates

• First Submitted: March 9, 2023
• First Submitted That Met QC Criteria: March 20, 2023
• First Posted (Actual): April 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: hypercholesterolemia; THR-β; non-alcoholic fatty liver disease(NAFLD)
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe
• Other Study ID Numbers: HSK31679-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No