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

NCT04774003 | Completed Phase 1 FDA Drug

• 1 other identifier: CKJX839A12105
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

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

Conditions

Hyperlipidemia

Keywords

Inclisiran; KJX839; LDL-C; Pharmacokinetics and pharmacodynamics; Chinese participants with elevated serum LDL-C

Outcome Measures

Primary Outcomes (6)

• PK parameters (Cmax) maximum peak observed plasma inclisiran concentration in treated participants

  Pharmacokinetics parameters of inclisiran

  0-48 hours post-dose

• PK parameters (Tmax) time to reach maximum peak plasma inclisiran concentration in treated participants

  Pharmacokinetics parameters of inclisiran

  0-48 hours post-dose

• PK parameters (T1/2) the elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve in inclisiran treated participants

  Pharmacokinetics parameters of inclisiran

  0-48 hours post-dose

• PK parameters (AUC) area under the plasma concentration-time curve in inclisiran treated participants

  Pharmacokinetics parameters of inclisiran

  0-48 hours post-dose

• Percentage change in Proprotein convertase subtilisin kexin 9 (PCSK9) from baseline overtime

  Pharmacodynamics effects of inclisiran

  Baseline to Days 5, 8, 15, 30, 60 and 90

• Percentage change in Low density lipoprotein cholesterol (LDL-C) from baseline overtime

  Pharmacodynamics effects of inclisiran

  Baseline to Days 5, 8, 15, 30, 60 and 90

Secondary Outcomes (3)

• 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

• 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

• Rate of formation of anti-drug antibodies to Inclisiran

  Baseline, Days 30 and 90

Study Arms (3)

300 mg inclisiran sodium (equivalent to 284 mg inclisiran)

EXPERIMENTAL

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

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

100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)

EXPERIMENTAL

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

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

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran) DRUG

100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran) in 0.5 mL solution. Subcutaneous administration at Day 1

Also known as: KJX839

100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran)

Placebo DRUG

Inclisiran sodium 0mg (equivalent to inclisiran 0 mg) in 1.5 mL solution. Subcutaneous administration at Day 1

Placebo

300 mg inclisiran sodium (equivalent to 284 mg inclisiran) DRUG

300 mg inclisiran sodium (equivalent to 284 mg inclisiran) in 1.5 mL solution. Subcutaneous administration at Day 1

Also known as: KJX839

300 mg inclisiran sodium (equivalent to 284 mg inclisiran)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained before any assessment is performed.
• Male or female participants ≥ 18 years of age at screening
• Participants should meet fasting serum LDL-C ≥ 100 mg/dL (≥ 2.6 mmol/L) at screening
• Participants should meet fasting triglyceride \< 400 mg/dL (\< 4.52 mmol/L) at screening
• Participants should be receiving a maximally tolerated dose of statin#.
• 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.
• 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)

You may not qualify if:

• 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;
• History of drug abuse or unhealthy alcohol use, malignancy of any organ system, or or allergy to the investigational compound/compound class;
• Major adverse cardiovascular event within 3 months prior to randomization;
• Calculated glomerular filtration rate ≤30 mL/min by estimated glomerular filtration rate (eGFR) using standardized clinical methodology;
• Use of other investigational drugs or planned use of other investigational products or devices;
• 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);
• Treatment with monoclonal antibodies inhibiting PCSK9 within 90 days prior to screening.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Novartis Investigative Site

Changsha, Hunan, 410003, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Beijing, 100029, China

Location

Related Publications (1)

• Luo Z, Huang Z, Sun F, Guo F, Wang Y, Kao S, Yang G, Huang J, Li J, Zhao S, He Y. The clinical effects of inclisiran, a first-in-class LDL-C lowering siRNA therapy, on the LDL-C levels in Chinese patients with hypercholesterolemia. J Clin Lipidol. 2023 May-Jun;17(3):392-400. doi: 10.1016/j.jacl.2023.04.010. Epub 2023 Apr 29.

  PMID: 37164838 DERIVED

Related Links

• A Plain Language Trial Summary is available on novctrd.com
• Results for CKJX839A12105 from the Novartis Clinical Trials Website

MeSH Terms

Conditions

Hyperlipidemias

Interventions

ALN-PCS

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a participant, investigator and sponsor blinded, randomized study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a placebo-controlled study of inclisiran sodium given as a single subcutaneous injection of either 100 mg and 300 mg.

Study Record Dates

• First Submitted: February 18, 2021
• First Posted: February 26, 2021
• Study Start: February 26, 2021
• Primary Completion: October 18, 2021
• Study Completion: October 18, 2021
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)