A Randomized Study to Evaluate the Effect of an "Inclisiran First" Implementation Strategy Compared to Usual Care in Patients With Atherosclerotic Cardiovascular Disease and Elevated LDL-C Despite Receiving Maximally Tolerated Statin Therapy (VICTORION-INITIATE)

(V-INITIATE Trial)

Recruiting at 80 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Statins

Must not be taking: PCSK9 inhibitors, Ezetimibe

Disqualifiers: Heart failure, Hypertension, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 90

Duration: 330 days

450 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires participants to be on the highest dose of statins they can tolerate. If you are statin intolerant, you can still participate if you've had side effects from at least two different statins.

How is the drug Inclisiran different from other treatments for its condition?

Inclisiran is unique because it is a small interfering RNA (siRNA) therapy that targets PCSK9, a protein involved in cholesterol regulation, and is administered via injection only twice a year, offering a novel approach compared to traditional cholesterol-lowering medications that require more frequent dosing. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing whether adding inclisiran to statin therapy helps adults with heart disease and high cholesterol better than usual care. Inclisiran helps lower bad cholesterol by aiding the liver in removing it from the blood.

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

Inclusion Criteria

Signed informed consent must be obtained prior to participation in the study

History of ASCVD, documented by hospital records, claims data and/or prior laboratory/imaging assessments

Serum LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL

Exclusion Criteria

An underlying known disease, or surgical, physical, or medical condition that, in the opinion of the investigator (or delegate) might interfere with interpretation of the clinical study results

You have had a bad reaction or allergy to any of the study treatments or their ingredients, or to similar drugs in the past.

Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with participation in the clinical study, and/or put the participant at significant risk (according to investigator's [or delegate] judgment) if he/she participates in the clinical study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Inclisiran is administered initially at randomization, 90 days later, and six months thereafter

330 days

Visits at randomization, Day 90, Day 180, and Day 330

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Inclisiran

Participant Groups

Group I: Inclisiran First Experimental Treatment 1 Intervention

Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care

Group II: Usual Care Active Control 1 Intervention

Treating physicians were recommended to treat patients in accordance with the 2018 ACC/AHA guidelines

Inclisiran is already approved in European Union, United States, China for the following indications:

Approved in European Union as Leqvio for:

• Primary hypercholesterolemia (heterozygous familial and non-familial)
• Mixed dyslipidemia

Approved in United States as Leqvio for:

• Heterozygous familial hypercholesterolemia (HeFH)
• Clinical atherosclerotic cardiovascular disease (ASCVD)
• Primary hypercholesterolemia

Approved in China as Leqvio for:

• Primary hypercholesterolemia (heterozygous familial and non-familial)
• Mixed dyslipidemia

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

References

1. United States pubmed.ncbi.nlm.nih.gov

Human beta interferon scaffold attachment region inhibits de novo methylation and confers long-term, copy number-dependent expression to a retroviral vector. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

COP9 signalosome subunit 6 binds and inhibits avian leukosis virus integrase. [2017]

3. England pubmed.ncbi.nlm.nih.gov

An avian leukosis virus subgroup J isolate with a Rous sarcoma virus-like 5'-LTR shows enhanced replication capability. [2020]

4. England pubmed.ncbi.nlm.nih.gov

A defective retroviral vector encoding human interferon-alpha2 can transduce human leukemic cell lines. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Genetics of the replication and maintenance functions of the hemolytic plasmid pSU316. Cloning of an IncFIII determinant. [2019]