Primary Hypercholesterolaemia and Mixed Dyslipidemia
Conditions
Brief summary
JS002 is a recombinant humanized anti-PCSK9 monoclonal antibody. This is a randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, PK/PD profile, immunogenicity as well as complete delivery of auto-injector by patients of JS002 as monotherapy in patients with primary hypercholesterolaemia and mixed dyslipidemia. In this study, two dose cohorts(150 mg, 450 mg) are set up, and 582 subjects are planned to be enrolled (randomizedly assigned to JS002 or placebo 150/450 mg group in a 2:1:2:1 ratio).A screening period (≤6 weeks), a double-blind treatment period (12 weeks), an open-label treatment period (40 weeks), and a follow-up period (8 weeks) will be required.
Interventions
DRUGJS002
JS002 will be administered per auto-injector. Participants will receive JS002 every 2 weeks subcutaneously.
DRUGPlacebo
Placebo will be administered per auto-injector. Participants will receive placebo every 2 weeks subcutaneously.
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent 2. Age 18\ 80 years old 3. Subject who has not achieve LDL-C goal as categorized by their CV risk at screening 4. Fasting TG≤4.5mmol/L by central laboratory at screening 5. Statin intolerance subject must have a history of statin intolerance as evidenced
Exclusion criteria
1. History of hemorrhagic stroke 2. NYHA III or IV heart failure, or known LVEF\< 30% within 1 year before randomization 3. Uncontrolled serious cardiac arrhythmia defined as recurrent and highly symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular response, or supraventricular tachycardia that are not controlled by medications, within 90 days prior to randomization 4. Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke, deep vein thrombosis or pulmonary embolism within 90 days prior to randomization 5. Planned cardiac surgery or revascularization 6. Uncontrolled hypertension defined as sitting systolic blood pressure(SBP) \> 160 mmHg or diastolic BP (DBP) \> 100 mmHg 7. Type 1 diabetes, poorly controlled type 2 diabetes (HbA1c \> 8%), newly diagnosed type 2 diabetes (within 90 days of randomization) 8. Others factors not suitable for participation judged by PI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in LDL-C at Week 12 | Baseline and week 12 | Percent Change From Baseline in LDL-C at Week 12 in statin intolerance subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in LDL-C at Week 12 | Baseline and week 12 | Change From Baseline in LDL-C at Week 12 in statin intolerance and ITT subjects |
| Percent Change From Baseline in LDL-C at Week 24,52 | Baseline and week 24,52 | Percent Change From Baseline in LDL-C at Week 24,52 in statin intolerance and ITT subjects |
| Change From Baseline in LDL-C at Week 24,52 | Baseline and week 24,52 | Change From Baseline in LDL-C at Week 24,52 in statin intolerance and ITT subjects |
| Percentage of Participants With LDL-C Less Than 1.8 mmol/L(70 mg/dL) | Baseline and week 12, 24, 52 | Percentage of Participants With LDL-C Less Than 1.8 mmol/L(70 mg/dL) at Week 12, 24, 52 in statin intolerance and ITT subjects |
| Percentage of Participants With Full Administration of JS002 | Baseline and week 12, 24, 52 | Percentage of Participants With Full Administration of JS002 at Weeks 12, 24, 52 in statin intolerance and ITT subjects |
| Percent Change From Baseline in other lipid parameters such as non-HDL-C, ApoB, TC, et al. at Week 12, 24, 52 | Baseline and week 12, 24, 52 | Percent Change From Baseline in other lipid parameters at Week 12, 24, 52 in statin intolerance and ITT subjects |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with anti-drug antibodies (ADAs) | From baseline to week 60 | Serum samples were analyzed for ADA. Positive samples were subsequently tested for neutralizing antibodies. |
Countries
China
Contacts
Primary ContactQiu'e Wan, PM
Outcome results
None listed