Study of Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Inclisiran in Chinese Participants With Elevated Serum LDL-C (ORION-14)

Novartis

Status and phase: Completed; Phase 1

Conditions: Hyperlipidemia

Treatments: Drug: Placebo; Drug: 300 mg inclisiran sodium (equivalent to 284 mg inclisiran); Drug: 100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04774003

CKJX839A12105

Details and patient eligibility

About

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

Full 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.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 3 patient groups, including a placebo group

300 mg inclisiran sodium (equivalent to 284 mg inclisiran)

Experimental group

Description:

300 mg inclisiran sodium (equivalent to 284 mg inclisiran) x 1 dose (n=15) at Day 1

Treatment:

Drug: 300 mg inclisiran sodium (equivalent to 284 mg inclisiran)

100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)

Experimental group

Description:

100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran) x 1 dose (n=15) at Day 1

Treatment:

Drug: 100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)

Placebo

Placebo Comparator group

Description:

Placebo x 1 dose (n=10) at Day 1

Treatment:

Drug: Placebo