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

Hyperlipidemia Clinical Trial

— ORION-14  

Official title:

A Placebo-controlled, Participant, Investigator and Sponsor Blinded, Randomized 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 (ORION-14)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04774003
• Other study ID #: CKJX839A12105
• Status: Completed
• Phase: Phase 1
• Start date: February 26, 2021
• Est. completion date: October 18, 2021

Study information

• Verified date: January 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: October 18, 2021
• Est. primary completion date: October 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hyperlipidemia
• Hyperlipidemias

Intervention

Drug:
• 100 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
• Placebo
Inclisiran sodium 0mg (equivalent to inclisiran 0 mg) in 1.5 mL solution. Subcutaneous administration at Day 1
• 300 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

Locations

Country	Name	City	State
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Chengdu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PK parameters (Cmax) maximum peak observed plasma inclisiran concentration in treated participants	Pharmacokinetics parameters of inclisiran	0-48 hours post-dose
Primary	PK parameters (Tmax) time to reach maximum peak plasma inclisiran concentration in treated participants	Pharmacokinetics parameters of inclisiran	0-48 hours post-dose
Primary	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
Primary	PK parameters (AUC) area under the plasma concentration-time curve in inclisiran treated participants	Pharmacokinetics parameters of inclisiran	0-48 hours post-dose
Primary	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
Primary	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	Percent change from baseline to Days 30, 60 and 90 in PD parameter Proprotein convertase subtilisin kexin 9 (PCSK9)	Pharmacodynamics differences between inclisiran and placebo	Baseline to Days 30, 60 and 90
Secondary	Percent change from baseline to Days 30, 60 and 90 in PD parameter Low density lipoprotein cholesterol (LDL-C)	Pharmacodynamics differences between inclisiran and placebo	Baseline to Days 30, 60 and 90
Secondary	Rate of formation of anti-drug antibodies to Inclisiran	Immunogenicity of inclisiran	Baseline, Days 30 and 90

External Links

•   A Plain Language Trial Summary is available on novctrd.com