Study of Efficacy and Safety of Inclisiran in Japanese Participants With High Cardiovascular Risk and Elevated LDL-C

NCT04666298 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CKJX839A11201
• Study Type: interventional
• Target: 312
• Locations: 1 country
• Sites: 42

Brief Summary

This was a placebo-controlled, double-blind, randomized trial in Japanese participants with history of coronary artery disease (CAD) or participants categorized in 'high risk' by JAS 2017 guideline, or Japanese participants with heterozygous familial hypercholesterolemia (HeFH) and elevated Low-density lipoprotein cholesterol (LDL-C) despite maximum tolerated dose of statin(s) to evaluate the efficacy, safety, tolerability, and PK of subcutaneous inclisiran injection(s).

Conditions

Hypercholesterolemia; Heterozygous Familial Hypercholesterolemia

Keywords

inclisiran; siRNA; dyslipidemia; PCSK9; Hypercholesterolemia; LDL-C

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) to Day 180

  Percent change from baseline in LDL-C was calculated to evaluate the effect of inclisiran at Day 180. Difference between different inclisiran dose groups and the placebo group in percentage change in LDL-C levels from baseline to Day 180 were calculated to capture both, the effect of the study drug and the effect of additional medications, mirroring the conditions in clinical practice. An MMRM (Mixed-effect Model with Repeated Measurement) was used as the primary analysis model, with treatment group, visits, interaction between visits and treatment groups, current use of statins or other lipid-modifying therapies as fixed effects, and baseline LDL-C as a continuous covariate.

  Baseline, Day 180

Secondary Outcomes (15)

• Percent Change From Baseline in PCSK9 by Visit

  Baseline, day 14, day 30, day 60, day 90, day 104, day 120, day 150, and day 180

• Percent Change From Baseline in LDL-C by Visit

  Baseline, day 14, day 30, day 60, day 90, day 104, day 120 and day 150

• Absolute Change in LDL-C From Baseline at Day 180

  Baseline, Day 180

• Proportion of Participants With LDL-C Greater Than 80% of Baseline Value at Day 180

  Baseline, Day 180

• Proportion of Participants With Greater or Equal to 50% LDL-C Reduction From Baseline by Visit

  Baseline, day 14, day 30, day 60, day 90, day 104, day 120, day 150, and day 180

Study Arms (4)

300 mg inclisiran sodium

EXPERIMENTAL

Subcutaneous injection

Drug: Inclisiran sodium

200 mg inclisiran sodium

EXPERIMENTAL

Subcutaneous injection

Drug: Inclisiran sodium

100 mg inclisiran sodium

EXPERIMENTAL

Subcutaneous injection

Drug: Inclisiran sodium

Placebo

PLACEBO COMPARATOR

Subcutaneous injection

Drug: Placebo

Interventions

Inclisiran sodium DRUG

Subcutaneously injected on Day 1, 90 and 270.

Also known as: KJX839

100 mg inclisiran sodium; 200 mg inclisiran sodium; 300 mg inclisiran sodium

Placebo DRUG

Subcutaneously injected on Day 1, 90, and 270.

Also known as: KJX839 placebo

Placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with history of CAD or participants categorized in 'high risk' by Japan Atherosclerosis Society (JAS) 2017 guidelines or participants with heterozygous familial hypercholesterolemia (HeFH)
• As per the JAS 2017 guideline, participants not meeting the LDL-C management targets.
• Participants on statins should be receiving a maximally tolerated dose.
• Participants not receiving statins must have documented evidence of intolerance to at least one statin.
• The lipid-lowering therapy should have remained stable for ≥ 30 days before screening with no planned medication/ dose change until Day 180

You may not qualify if:

• Participants diagnosed with homozygous familial hypercholesterolemia (HoFH).
• Treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9.
• New York Heart Association (NYHA) class IV heart failure or last known left ventricular ejection fraction \<25%.
• Cardiac arrhythmia within 3 months prior to randomization that is not controlled by medication or via ablation.
• Uncontrolled hypertension: systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg prior to randomization despite antihypertensive therapy.
• Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), \>3x the upper limit of normal (ULN), or total bilirubin \>2x ULN at screening.
• Severe concomitant non-cardiovascular disease that carries the risk of reducing life expectancy to less than 2 years.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (42)

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Location

Novartis Investigative Site

Matsudo, Chiba, 271 0077, Japan

Location

Novartis Investigative Site

Itoshima, Fukuoka, 819-1104, Japan

Location

Novartis Investigative Site

Kitakyushu, Fukuoka, 800-0057, Japan

Location

Novartis Investigative Site

Kitakyushu, Fukuoka, 804-0025, Japan

Location

Novartis Investigative Site

Kitakyushu, Fukuoka, 805-8508, Japan

Location

Novartis Investigative Site

Kitakyushu, Fukuoka, 806-8501, Japan

Location

Novartis Investigative Site

Nakagawa, Fukuoka, 811-1244, Japan

Location

Novartis Investigative Site

Sapporo, Hokkaido, 006-8555, Japan

Location

Novartis Investigative Site

Sapporo, Hokkaido, 062-8618, Japan

Location

Novartis Investigative Site

Sashima-gun, Ibaraki, 306-0433, Japan

Location

Novartis Investigative Site

Tsuchiura, Ibaraki, 300-0028, Japan

Location

Novartis Investigative Site

Kahoku-gun, Ishikawa-ken, 920-0293, Japan

Location

Novartis Investigative Site

Kanazawa, Ishikawa-ken, 920 8650, Japan

Location

Novartis Investigative Site

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

Novartis Investigative Site

Komatsu, Ishikawa-ken, 923-0961, Japan

Location

Novartis Investigative Site

Takamatsu, Kagawa-ken, 760 8557, Japan

Location

Novartis Investigative Site

Fujisawa, Kanagawa, 251-0041, Japan

Location

Novartis Investigative Site

Kawasaki, Kanagawa, 216-8511, Japan

Location

Novartis Investigative Site

Kuse, Kyoto, 613-0034, Japan

Location

Novartis Investigative Site

Sendai, Miyagi, 983-0039, Japan

Location

Novartis Investigative Site

Ōmura, Nagasaki, 856-8562, Japan

Location

Novartis Investigative Site

Izumisano, Osaka, 598-8577, Japan

Location

Novartis Investigative Site

Matsubara, Osaka, 580-0032, Japan

Location

Novartis Investigative Site

Osaka, Osaka, 530 0001, Japan

Location

Novartis Investigative Site

Osaka, Osaka, 540-0006, Japan

Location

Novartis Investigative Site

Osaka, Osaka, 543-0035, Japan

Location

Novartis Investigative Site

Suita, Osaka, 564-8565, Japan

Location

Novartis Investigative Site

Suita, Osaka, 565-0853, Japan

Location

Novartis Investigative Site

Iruma-gun, Saitama, 350-0495, Japan

Location

Novartis Investigative Site

Sayama, Saitama, 350-1305, Japan

Location

Novartis Investigative Site

Chiyoda City, Tokyo, Japan

Location

Novartis Investigative Site

Chuo-ku, Tokyo, 103-0027, Japan

Location

Novartis Investigative Site

Chuo-ku, Tokyo, 103-0028, Japan

Location

Novartis Investigative Site

Nerima-ku, Tokyo, 176-8530, Japan

Location

Novartis Investigative Site

Shinagawa-ku, Tokyo, 142-8666, Japan

Location

Novartis Investigative Site

Shinjuku Ku, Tokyo, 160-0008, Japan

Location

Novartis Investigative Site

Chuoh-ku, 104-0031, Japan

Location

Novartis Investigative Site

Gifu, 500-8384, Japan

Location

Novartis Investigative Site

Kyoto, 612-8555, Japan

Location

Novartis Investigative Site

Ōita, 870-8511, Japan

Location

Novartis Investigative Site

Saga, 840-8571, Japan

Location

Related Publications (1)

• Warden BA, Duell PB. Inclisiran: A Novel Agent for Lowering Apolipoprotein B-containing Lipoproteins. J Cardiovasc Pharmacol. 2021 Aug 1;78(2):e157-e174. doi: 10.1097/FJC.0000000000001053.

  PMID: 33990512 DERIVED

Related Links

• Patient Lay Trial Summary

MeSH Terms

Conditions

Hypercholesterolemia; Dyslipidemias

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2020
• First Posted: December 14, 2020
• Study Start: January 29, 2021
• Primary Completion: April 18, 2022
• Study Completion: October 19, 2022
• Last Updated: June 20, 2024
• Results First Posted: May 10, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share

Locations

JP (42)