Efficacy and Safety of Inclisiran as Monotherapy in Patients With Primary Hypercholesterolemia Not Receiving Lipid-lowering Therapy. (V-Mono)

• ClinicalTrials.gov Identifier: NCT05763875
• Recruitment Status: Active, not recruiting
• First Posted: March 10, 2023
• Last Update Posted: May 16, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: February 28, 2023
• First Posted Date: March 10, 2023
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: March 15, 2023
• Estimated Primary Completion Date: June 21, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2023)

• Percentage change in Low-density Lipoprotein Cholesterol (LDL-C) from Baseline to Day 150 compared with placebo [ Time Frame: Baseline, Day 150 ]
  Percentage change in LDL-C from Baseline (Day 1) to Day 150 comparing Inclisiran arm versus Placebo arm
• Percentage change in LDL-C from Baseline to Day 150 compared with ezetimibe [ Time Frame: Baseline, Day 150 ]
  Percentage change in LDL-C from Baseline (Day 1) to Day 150 comparing Inclisiran arm versus Ezetimibe arm.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 28, 2023)

• Absolute change in LDL-C from Baseline to Day 150 [ Time Frame: Baseline, Day 150 ]
  Absolute change in LDL-C from Baseline (Day 1) to Day 150 compared to ezetimibe and placebo
• Percentage change in Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) from Baseline to Day 150 [ Time Frame: Baseline, Day 150 ]
  Percentage change in PCSK9 from Baseline (Day 1) and Day 150 compared to ezetimibe and placebo
• Percentage change in non-High-Density Lipoprotein Cholesterol (non-HDL-C) from Baseline to Day 150 [ Time Frame: Baseline, Day 150 ]
  Percentage change in non-HDL-C from Baseline (Day 1) and Day 150 compared to ezetimibe and placebo
• Percentage change in Total Cholesterol (TC)/HDL-C ratio from Baseline to Day 150 [ Time Frame: Baseline, Day 150 ]
  Percentage change in total cholesterol (TC)/HDL-C ratio from Baseline (Day 1) and Day 150 compared to ezetimibe and placebo
• Percentage change in Apolipoprotein B (Apo B) from Baseline to Day 150 [ Time Frame: Baseline, Day 150 ]
  Percentage change in Apo B from Baseline (Day 1) and Day 150 compared to ezetimibe and placebo
• Percentage change in Apo B/Apo A-1 ratio from Baseline to Day 150 [ Time Frame: Baseline, Day 150 ]
  Percentage change in Apo B/Apo A-1 ratio from baseline (Day 1) and Day 150 compared to ezetimibe and placebo
• Percentage change in Lipoprotein (a) [Lp(a)] from Baseline to Day 150 [ Time Frame: Baseline, Day 150 ]
  Percentage change in Lp(a) from Baseline (Day 1) and Day 150 compared to ezetimibe and placebo

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of Inclisiran as Monotherapy in Patients With Primary Hypercholesterolemia Not Receiving Lipid-lowering Therapy.
• Official Title: A Double-blind, Randomized, Placebo- and Active-Comparator Controlled Study to Evaluate the Efficacy of Inclisiran as Monotherapy in Patients With Primary Hypercholesterolemia Not Receiving Lipid-Lowering Therapy (VictORION-Mono)
• Brief Summary: CKJX839D12304 is a research study to determine if the study treatment, called inclisiran, in comparison to placebo or ezetimibe can effectively reduce LDL-C as measured by percentage change from baseline to Day 150. This study is being conducted in eligible participants with primary hypercholesterolemia not receiving any lipid-lowering therapy (LLT), with a 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk of less than 7.5%.

Detailed Description

This study is a randomized, double-blind, placebo- and active comparator-controlled, multicenter study in 300 adult participants with primary hypercholesterolemia not receiving any LLT with a 10-year ASCVD risk score of less than 7.5%. This study will evaluate the efficacy and safety of inclisiran sodium 300 mg, administered as a monotherapy in comparison to ezetimibe and placebo.

The study consists of:

• a screening period of up to 14 days;
• a double-blind treatment period of 150+/- 5 days during which participants will be randomly assigned to either the inclisiran arm, the ezetimibe arm or the placebo arm in a 2:1:1 ratio; and
• a safety follow-up / End of Study visit conducted 30+5 days after the Day 150 visit.

The overall study duration is approximately 190 days.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Multi-center, randomized, double-blind, placebo-controlled, parallel groups

Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

Sponsor Personnel participating in the study conduct will also be blinded.

Primary Purpose: Treatment

• Condition: Hypercholesterolemia

Intervention

• Drug: Inclisiran
  284 mg (equivalent to 300 mg inclisiran sodium) subcutaneous injection given on Day 1 and Day 90
  Other Name: KJX839
• Drug: Ezetimibe
  10 mg over-encapsulated tablet taken once a day from Day 1 through Day 149
  Other Name: Sandoz ezetimibe
• Drug: Matching Placebo for Inclisiran
  0mg placebo injection solution for subcutaneous injection on Day 1 and Day 90
  Other Name: Placebo s.c.
• Drug: Matching Placebo for Ezetimibe
  0mg over-encapsulated placebo tablet taken once a day from Day 1 through Day 149
  Other Name: Placebo p.o.

Study Arms

• Experimental: Inclisiran
  Inclisiran s.c and Placebo p.o
  Interventions:

  • Drug: Inclisiran
  • Drug: Matching Placebo for Ezetimibe
• Active Comparator: Ezetimibe
  Placebo s.c. and Ezetimibe p.o.
  Interventions:

  • Drug: Ezetimibe
  • Drug: Matching Placebo for Inclisiran
• Placebo Comparator: Placebo
  Placebo s.c. and Placebo p.o.
  Interventions:

  • Drug: Matching Placebo for Inclisiran
  • Drug: Matching Placebo for Ezetimibe

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 15, 2024): 350
• Original Estimated Enrollment (submitted: February 28, 2023): 300
• Estimated Study Completion Date: June 21, 2024
• Estimated Primary Completion Date: June 21, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria to be met at screening:

• informed consent must be signed prior to participation in study
• fasting LDL-C of >= 100mg/dL but < 190mg/dL
• fasting triglycerides <= 400 mg/dL
• 10-year ASCVD risk score < 7.5%
• not on any lipid-lowering therapy within 90 days

Key Exclusion Criteria:

• history of ASCVD
• diabetes mellitus or fasting plasma glucose of >= 7.0 mmol/L or HbA1c >= 6.5%
• secondary hypercholesterolemia, e.g. hypothyroidism (TSH above upper limit of normal)

Other protocol-defined inclusion/exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Colombia, Germany, Hungary, Mexico, United States

Administrative Information

• NCT Number: NCT05763875
• Other Study ID Numbers: CKJX839D12304
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: May 2024