Clinical trial NCT05795517: Study of HSK31679 in Subjects With Hypercholesterolemia With Nonalcoholic Fatty Liver Disease（NAFLD）
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Keywords: hypercholesterolemia
non-alcoholic fatty liver disease(NAFLD)
THR-β
Lead sponsor: Haisco Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-04-03
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Percentage change in LDL-C from baseline at 12 week;
timeFrame: Baseline and Week 12
measure: Percentage change in MRI-PDFF from baseline at 12 week；
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Percentage change in fasting LDL-C from baseline;
timeFrame: Week2,4,8
measure: The proportion of patients with MRI-PDFF decreased by > 30%
timeFrame: Baseline and Week 12
measure: Proportion of patients with LDL-C<3.34mmol/L（<130mg/dL）
timeFrame: Baseline and Week 12
measure: Percentage change of fasting TG from baseline;
timeFrame: Week2,4,8,12
measure: Percentage change of fasting TC from baseline;
timeFrame: Week2,4,8,12
measure: Percentage change of fasting HDL-C from baseline;
timeFrame: Week2,4,8,12
measure: Percentage change in body weight from baseline
timeFrame: Baseline and Week 12
measure: AUC0-τ of HSK31679 (All subjects)
timeFrame: up to 2,4,7 weeks
measure: Cmax of HSK31679 (All subjects)
timeFrame: up to 2,4,7 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tsinghua Changgung Hospital, Tsinghua University
Study officials:
References: