Hyperlipidemia
Conditions
Keywords
Inclisiran, KJX839, LDL-C, Pharmacokinetics and pharmacodynamics, Chinese participants with elevated serum LDL-C
Brief summary
Study to evaluate the pharmacokinetics and pharmacodynamics of inclisiran treatment given as single subcutaneous injection in Chinese participants with elevated low-density lipoprotein cholesterol (LDL-C) despite treatment with LDL-C lowering therapies
Detailed description
The purpose of the study is to characterize pharmacokinetics, pharmacodynamics, safety and tolerability of inclisiran in Chinese participants with elevated serum LDL-C to support inclisiran registration in China.Inclisiran is a long acting RNA therapeutic agent that inhibits the synthesis of PCSK9, leading to reduced circulating LDL-C levels. Three pivotal Phase III studies have been conducted primarily in non-Asian participants to support New Drug Application/Marketing Authorization Application approval of inclisiran globally. This study design is based on the hypothesis that the global inclisiran clinical data primarily obtained in Caucasian participants could be appropriately extrapolated to Chinese participants.
Interventions
DRUG100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)
100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran) in 0.5 mL solution. Subcutaneous administration at Day 1
DRUGPlacebo
Inclisiran sodium 0mg (equivalent to inclisiran 0 mg) in 1.5 mL solution. Subcutaneous administration at Day 1
DRUG300 mg inclisiran sodium (equivalent to 284 mg inclisiran)
300 mg inclisiran sodium (equivalent to 284 mg inclisiran) in 1.5 mL solution. Subcutaneous administration at Day 1
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is a participant, investigator and sponsor blinded, randomized study
Intervention model description
This is a placebo-controlled study of inclisiran sodium given as a single subcutaneous injection of either 100 mg and 300 mg.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent must be obtained before any assessment is performed. 2. Male or female participants ≥ 18 years of age at screening 3. Participants should meet fasting serum LDL-C ≥ 100 mg/dL (≥ 2.6 mmol/L) at screening 4. Participants should meet fasting triglyceride \< 400 mg/dL (\< 4.52 mmol/L) at screening 5. Participants should be receiving a maximally tolerated dose of statin#. 6. For all participants, all the lipid-lowering therapy/ies (such as but not limited to statins and/or ezetimibe) should have remained stable (stable dose and no medication change) for ≥ 30 days before screening with no planned medication or dose change during study participation. #Maximum tolerated dose was defined as the maximum dose of statin that could be taken on a regular basis without intolerable AEs. 7. Participants not receiving statin must have a documented evidence of intolerance to all doses of at least 2 different statins (or the corresponding local definition of complete intolerance to statins)
Exclusion criteria
1. Participants diagnosed with any of following: homozygous familial hypercholesterolemia, New York Heart Association class III & IV heart failure, Type 2 diabetes, severe hypertension, active liver disease, HIV infection or any uncontrolled or serious disease; 2. History of drug abuse or unhealthy alcohol use, malignancy of any organ system, or or allergy to the investigational compound/compound class; 3. Major adverse cardiovascular event within 3 months prior to randomization; 4. Calculated glomerular filtration rate ≤30 mL/min by estimated glomerular filtration rate (eGFR) using standardized clinical methodology; 5. Use of other investigational drugs or planned use of other investigational products or devices; 6. Women of child-bearing potential unless they are using basic methods of contraception during dosing of investigational drug (total abstinence, sterilization, barrier methods, hormonal contraception, intrauterine device); 7. Treatment with monoclonal antibodies inhibiting PCSK9 within 90 days prior to screening. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change in Low density lipoprotein cholesterol (LDL-C) from baseline overtime | Baseline to Days 5, 8, 15, 30, 60 and 90 | Pharmacodynamics effects of inclisiran |
| PK parameters (T1/2) the elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve in inclisiran treated participants | 0-48 hours post-dose | Pharmacokinetics parameters of inclisiran |
| PK parameters (AUC) area under the plasma concentration-time curve in inclisiran treated participants | 0-48 hours post-dose | Pharmacokinetics parameters of inclisiran |
| Percentage change in Proprotein convertase subtilisin kexin 9 (PCSK9) from baseline overtime | Baseline to Days 5, 8, 15, 30, 60 and 90 | Pharmacodynamics effects of inclisiran |
| PK parameters (Cmax) maximum peak observed plasma inclisiran concentration in treated participants | 0-48 hours post-dose | Pharmacokinetics parameters of inclisiran |
| PK parameters (Tmax) time to reach maximum peak plasma inclisiran concentration in treated participants | 0-48 hours post-dose | Pharmacokinetics parameters of inclisiran |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent change from baseline to Days 30, 60 and 90 in PD parameter Low density lipoprotein cholesterol (LDL-C) | Baseline to Days 30, 60 and 90 | Pharmacodynamics differences between inclisiran and placebo |
| Rate of formation of anti-drug antibodies to Inclisiran | Baseline, Days 30 and 90 | Immunogenicity of inclisiran |
| Percent change from baseline to Days 30, 60 and 90 in PD parameter Proprotein convertase subtilisin kexin 9 (PCSK9) | Baseline to Days 30, 60 and 90 | Pharmacodynamics differences between inclisiran and placebo |
Countries
China
Outcome results
None listed