Inclisiran for Cardiovascular Disease with High Cholesterol

(V-INITIATE Trial)

No longer recruiting at 81 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new strategy for individuals with atherosclerotic cardiovascular disease, a condition where arteries become clogged with fat, cholesterol, and other substances, who still have high levels of LDL cholesterol despite taking the strongest statin dose possible. The trial compares two groups: one adds inclisiran, a medication that lowers cholesterol, to their treatment plan immediately, while the other continues with usual care. Suitable candidates for this trial include those with a history of heart disease or stroke who maintain high LDL cholesterol levels despite the strongest tolerable statin dose. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

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.

Is there any evidence suggesting that inclisiran is likely to be safe for humans?

Research has shown that inclisiran is safe to use. Studies have found that people can take inclisiran long-term without issues. For over six years, no new safety concerns have emerged in patients using inclisiran. This reliable safety information comes from several studies, including ORION-10 and ORION-11. These results suggest that inclisiran is generally safe for individuals with heart disease and high levels of LDL-C (bad cholesterol) who are already taking statins. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Inclisiran is unique because it offers a new approach to managing atherosclerotic cardiovascular disease with elevated LDL-C levels. Most current treatments, like statins, work by inhibiting cholesterol production in the liver. Inclisiran, on the other hand, uses RNA interference technology to target the PCSK9 protein, which enhances the liver's ability to remove LDL cholesterol from the blood. This innovative mechanism not only provides an additional option for patients who don't respond adequately to statins but also offers the convenience of less frequent dosing, potentially improving adherence to treatment. Researchers are excited about inclisiran because it represents a promising advancement in cholesterol management, with the potential to reduce cardiovascular events more effectively.

What evidence suggests that inclisiran might be an effective treatment for ASCVD?

Research has shown that inclisiran, which participants in this trial may receive, effectively lowers LDL cholesterol, often referred to as "bad" cholesterol. One study found that inclisiran reduced LDL cholesterol levels by 52.6% within 180 days. Another study showed that 85% of patients taking inclisiran reached their cholesterol goals, compared to just 31% of those not taking it. These results are significant for people with heart disease, as high LDL cholesterol is a major risk factor. The evidence suggests that inclisiran can be a powerful addition to standard treatments for managing cholesterol levels. ^{6 7 8 9 10}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Inclisiran

How Is the Trial Designed?

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

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11907238/

Safety and Efficacy of Inclisiran in Hyperlipidemia 3.3.​​ The use of inclisiran significantly reduced the % of total cholesterol levels when compared to the control group (MD = −31.22, 95% CI: −33 ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1912387

Two Phase 3 Trials of Inclisiran in Patients with Elevated ... In one trial, the LDL cholesterol level was lowered by 52.6% at 180 days after two doses of 284 mg of inclisiran (equivalent to 300 mg of inclisiran sodium) ...

3. novartis.com novartis.com/news/media-releases/novartis-leqvio-shows-statistically-significant-and-clinically-meaningful-early-ldl-c-goal-achievement-less-muscle-pain

Novartis Leqvio® shows statistically significant and ... After 90 days of treatment with Leqvio on top of LLT, 85% of patients achieved their guideline-recommended LDL-C target compared to 31% of those ...

4. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK595412/

Inclisiran (Leqvio) - NCBI Bookshelf - NIH Evidence from 3 clinical trials showed that treatment with Leqvio lowered bad cholesterol (LDL-C) in adults with HeFH or nFH with ASCVD who were already being ...

5. thelancet.com thelancet.com/journals/landia/article/PIIS2213-8587(22)00353-9/fulltext

Long-term efficacy and safety of inclisiran in patients with ... In the inclisiran-only arm, LDL cholesterol was reduced by 47·5% (95% CI 50·7–44·3) at day 210 and sustained over 1440 days. The 4-year averaged ...

6. leqviohcp.com leqviohcp.com/safety

well-tolerated safety profile 1 - LEQVIO® (inclisiran) | HCP Consistent safety profile beyond 6 years · Long-term safety data were consistent with phase 3 clinical trials · No new safety signals ...

7. pro.novartis.com pro.novartis.com/uk-en/medicines/cardio-metabolic/leqvio/safety-profile

LEQVIO®▼ (inclisiran) Safety Profile | Novartis Pro Portal LEQVIO®▽ (inclisiran) safety profile. Safety data from the ORION-10 and ORION-11 trials. For UK healthcare professionals only.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/214012lbl.pdf

LEQVIO® (inclisiran) injection, for subcutaneous use There are no available data on the use of LEQVIO in pregnant patients to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse ...

9. jacc.org jacc.org/doi/10.1016/j.jacc.2023.10.007

Safety and Tolerability of Inclisiran for Treatment ... Long-term treatment with inclisiran was well tolerated in a diverse population, without new safety signals, supporting the safety of inclisiran in patients ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11511047/

Safety of Inclisiran: A Disproportionality Analysis from the ... In this study, we evaluated the safety profile of inclisiran using the ICSR data from the EV database and compared it to those related to PCSK9-As. Inclisiran ...