Pelacarsen for Cardiovascular Disease

(ADD-VANTAGE Trial)

Recruiting at 42 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Inclisiran

Must not be taking: PCSK9 inhibitors

Disqualifiers: Uncontrolled hypertension, Heart failure, Malignancy, others

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

Compensation: Varies

Number of Visits: 12

Duration: 6 months

340 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called pelacarsen to determine its effectiveness for people with heart disease who have high levels of lipoprotein(a), or Lp(a), in their blood. Researchers aim to assess whether pelacarsen is safe, effective, and well-tolerated compared to a placebo. Participants should have existing heart conditions such as coronary heart disease, be on cholesterol-lowering medication, and have elevated Lp(a) levels. As a Phase 3 trial, this represents the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment for heart disease.

Do I have to stop taking my current medications for the trial?

The trial requires participants to be on a stable dose of lipid-lowering therapy and standard care for other cardiovascular risk factors for at least 30 days before starting. It doesn't specify stopping other medications, but you must not have used certain medications like PCSK9 inhibitors recently.

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

Previous studies have shown that pelacarsen is safe and well-tolerated. Research indicates that pelacarsen effectively lowers lipoprotein(a) levels, which are linked to heart disease. In one study, 98% of patients experienced a drop in their lipoprotein(a) levels below the risky threshold, suggesting the treatment works well without causing major issues.

Additionally, another study found pelacarsen safe even for individuals with mild health issues, with side effects generally mild. This research strongly suggests that pelacarsen is generally safe for human use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cardiovascular disease?

Pelacarsen is unique because it targets lipoprotein(a) [Lp(a)], a specific type of cholesterol particle that has been linked to cardiovascular disease but isn't effectively addressed by current standard treatments like statins, which primarily focus on lowering LDL cholesterol. This makes Pelacarsen stand out as it directly reduces Lp(a) levels, potentially offering a new avenue for reducing cardiovascular risks that other treatments can't address. Researchers are excited because this targeted approach could lead to better outcomes for patients with elevated Lp(a) levels, a group that currently has limited treatment options.

What evidence suggests that pelacarsen might be an effective treatment for cardiovascular disease?

Research has shown that pelacarsen, which participants in this trial may receive, can effectively lower levels of lipoprotein(a) (Lp(a)), a factor linked to heart disease. Studies indicate that pelacarsen reduces Lp(a) levels below the risk threshold for heart problems in 98% of patients. Specifically, it has lowered the risk of heart disease compared to a placebo. For individuals with high Lp(a), pelacarsen might help prevent heart issues. Pelacarsen works by targeting and reducing specific proteins in the blood that contribute to heart problems. Overall, early findings are promising for its use in managing heart disease. ^{2 4 6 7 8}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for people with cardiovascular disease who have high levels of a fat-protein particle called Lp(a) and are already taking Inclisiran for high LDL cholesterol. They must have stable heart disease, stroke history, or blocked arteries and be on consistent lipid-lowering therapy and other treatments for related conditions like hypertension or diabetes.

Inclusion Criteria

I completed the initial treatment phase with inclisiran.

My Lp(a) levels are 175 nmol/L or higher.

My LDL cholesterol level is above 70 mg/dL.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either pelacarsen or placebo subcutaneous injections once monthly

6 months

6 visits (in-person)

Open-label Treatment

All participants receive pelacarsen 80 mg injection once monthly

6 months

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

What Are the Treatments Tested in This Trial?

Interventions

• Inclisiran
• Pelacarsen

Trial Overview

The study tests the effectiveness of Pelacarsen compared to a placebo in lowering Lp(a) levels among participants with established arterial plaque buildup who are also receiving Inclisiran. The goal is to see if adding Pelacarsen can further reduce cardiovascular risks.

How Is the Trial Designed?

Group I: Pelacarsen Active Control 2 Interventions

Participants randomized in Pelacarsen arm, will be administered pelacarsen (TQJ230) subcutaneous injection once monthly for 12 months.

Group II: Placebo Placebo Group 3 Interventions

Participants will be administered placebo subcutaneous injection once monthly for 6 months. After Month 6, all participants will receive pelacarsen 80 mg injection for the remaining 6 months during the open-label treatment period.

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.

jacc.org

jacc.org/doi/10.1016/j.jacc.2021.12.032

Effect of Pelacarsen on Lipoprotein(a) Cholesterol and ...

Pelacarsen significantly lowers direct Lp(a)-C and has neutral to mild lowering of LDL-C corr. In patients with elevated Lp(a), LDL-C corr provides a more ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04023552

NCT04023552 | Assessing the Impact of Lipoprotein (a) ...

Demonstrate the superiority of pelacarsen (TQJ230) compared to placebo in reducing the risk of the composite of coronary heart disease (CHD) outcomes: death due ...

3.

ir.ionis.com

ir.ionis.com/news-releases/news-release-details/ionis-announces-enrollment-completion-phase-3-lpa-horizon

Ionis announces enrollment completion of Phase 3 Lp(a) ...

Data from a Phase 2 study showed pelacarsen reduced Lp(a) levels below the recommended threshold of risk for CVD events (<50 mg/dL, <125 nmol/L) in 98% of ...

4.

novartis.com

novartis.com/clinicaltrials/study/nct06813911

Lp(a) Lowering Study of Pelacarsen (TQJ230) With ...

The purpose of the study CTQJ230A12304, is to evaluate the efficacy, safety, and tolerability of pelacarsen (TQJ230) compared to placebo in ...

5.

natap.org

natap.org/2022/HIV/090322_04.htm

Antisense Drug Reduced LPa; in Phase 3 Study Assessing ...

Lp(a) HORIZON is evaluating the safety and efficacy of pelacarsen in reducing cardiovascular events in patients with cardiovascular disease and elevated levels ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04023552

NCT04023552 | Assessing the Impact of Lipoprotein (a) ...

This is a pivotal phase 3 study designed to support an indication for the reduction of cardiovascular risk in patients with established CVD and elevated Lp(a)

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S0002870325001012

Design and Rationale of Lp(a)HORIZON Trial: Assessing ...

Pelacarsen significantly reduced Lp(a) in a dose-dependent manner with mean percent decrease of 35% at 20 mg every 4 weeks, 56% for 40 mg every 4 weeks, 58% for ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12478598/

Pharmacokinetics and Safety of Pelacarsen, a GalNAc3

The results of this phase I study support that pelacarsen is safe and well tolerated in participants with mild HI. Additionally, mild HI had ...