Pelacarsen for Cardiovascular Disease

Not currently recruiting at 122 trial locations

Overseen By Awawu Igbinadolor

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: LDL-C lowering

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: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new treatment, pelacarsen (TQJ230), can reduce the risk of heart problems in US Black/African American and Hispanic individuals with cardiovascular disease and high levels of a specific protein in their blood, known as Lp(a). The study compares pelacarsen with a placebo to determine which is more effective and safe. Suitable participants have heart or blood vessel issues and are already managing their cholesterol and blood pressure. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, you must be on stable therapy for cardiovascular risk factors like LDL-C, blood pressure, and diabetes according to local guidelines.

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

Research has shown that pelacarsen is likely safe to use. In an earlier study, patients who took pelacarsen, also known as AKCEA-APO(a)-LRx, generally tolerated it well. Participants experienced a reduction in lipoprotein(a) levels by 35-80%, depending on the dose. These reductions occurred without major safety issues, indicating that pelacarsen is both effective and safe for humans. While side effects can occur with any treatment, current evidence suggests pelacarsen is well-tolerated in people with heart-related conditions. ^{1 2 3 4 5}

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

Pelacarsen (TQJ230) is unique because it targets lipoprotein(a), a specific type of cholesterol particle that has been difficult to address with existing treatments for cardiovascular disease. Most current options, like statins, focus on reducing LDL cholesterol but don't specifically tackle lipoprotein(a). Pelacarsen uses a novel antisense oligonucleotide mechanism, which means it can decrease the production of lipoprotein(a) at the genetic level. This direct approach offers a promising new strategy for reducing cardiovascular risk in patients where traditional therapies fall short. Researchers are excited about its potential to provide a more targeted and effective solution for managing heart disease.

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 lipoprotein(a), or Lp(a), levels in the blood. High Lp(a) levels are linked to an increased risk of heart disease. In earlier studies, pelacarsen reduced Lp(a) levels by 35–80% in patients with heart conditions. Patients tolerated pelacarsen well, with no major safety issues reported. These findings suggest that pelacarsen could be a promising treatment for reducing heart disease risk in people with high Lp(a) levels. ^{1 3 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 US Black/African American and Hispanic individuals aged 18 to 80 with high Lp(a) levels and existing cardiovascular disease. They must be on stable standard treatments for other risk factors like LDL cholesterol, blood pressure, and diabetes.

Inclusion Criteria

Lp(a) ≥ 125 nmol/L at the screening visit, measured at the Central laboratory

I am on stable treatment for cholesterol, blood pressure, or diabetes.

I have a history of heart or blood vessel disease.

Exclusion Criteria

Platelet count <140,000 per mm3

Pregnant or nursing women

I have liver disease or my liver isn't working properly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pelacarsen (TQJ230) 80 mg s.c. QM or placebo for 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pelacarsen (TQJ230)

Trial Overview The study tests the effectiveness of Pelacarsen (TQJ230), a medication given as an injection once a month, against a placebo in reducing cardiovascular risk by lowering Lp(a) levels in participants.

How Is the Trial Designed?

Group I: TQJ230 Experimental Treatment 1 Intervention

TQJ230 80mg QM s.c.

Group II: Placebo Placebo Group 1 Intervention

Matching placebo.

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

Published Research Related to This Trial

New RNA-based therapeutics, particularly the antisense oligonucleotide pelacarsen, have shown promising results in significantly lowering lipoprotein (a) [Lp(a)] levels by over 90% in clinical trials, indicating their potential efficacy in reducing cardiovascular risk.

These therapies have demonstrated a satisfactory safety profile and are currently in various stages of clinical development, with pelacarsen reaching phase 3 trials, suggesting a strong future for targeted Lp(a) reduction in patients at risk for atherosclerotic cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Novel RNA-Targeting Agents for Effective Lipoprotein(a) Lowering: A Systematic Assessment of the Evidence From Completed and Ongoing Developmental Clinical Trials. Milosavljevic, MN., Stefanovic, SM., Pejcic, AV.[2023]

Volanesorsen, an antisense oligonucleotide targeting APOC3 mRNA, significantly reduces both apolipoprotein-CIII production and triglyceride levels, making it a promising treatment for severe hypertriglyceridemia.

Current phase 3 trials are evaluating the efficacy and safety of volanesorsen, which could provide a new option for patients at risk of pancreatitis and cardiovascular disease due to high triglyceride levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of antisense oligonucleotide therapy against apolipoprotein-CIII in hypertriglyceridemia. Gouni-Berthold, I.[2018]

Pelacarsen, an antisense oligonucleotide targeting the LPA gene, has been shown to safely and effectively reduce lipoprotein(a) levels by 35-80% in patients with cardiovascular disease, which is promising for managing cardiovascular risk in chronic kidney disease (CKD) patients.

However, the Phase 2 and upcoming Phase 3 trials exclude patients with significant kidney disease, limiting the understanding of pelacarsen's efficacy in CKD populations, where elevated Lp(a) levels are a concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pelacarsen for lowering lipoprotein(a): implications for patients with chronic kidney disease. Fernandez-Prado, R., Perez-Gomez, MV., Ortiz, A.[2023]

Pelacarsen is safe and well-tolerated in healthy Japanese subjects, with no serious adverse events reported during the study involving 29 participants.

The treatment significantly reduced lipoprotein(a) [Lp(a)] levels, achieving up to an 84% reduction with monthly doses of 80 mg, indicating its potential efficacy in managing cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pelacarsen in lowering Lp(a) in healthy Japanese subjects. Karwatowska-Prokopczuk, E., Lesogor, A., Yan, JH., et al.[2023]

Patients with high levels of lipoprotein(a) [Lp(a)] are at increased risk for serious cardiovascular diseases, but there are currently no FDA-approved treatments specifically targeting Lp(a).

Research is ongoing into pelacarsen as a potential therapy to lower Lp(a) levels, which may help reduce cardiovascular events in at-risk populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of the Clinical Pharmacology of Pelacarsen: A Lipoprotein(a)-Lowering Agent. Hardy, J., Niman, S., Goldfaden, RF., et al.[2022]

Citations

1. ir.ionis.com ir.ionis.com/news-releases/news-release-details/phase-2-results-akcea-apoa-lrx-presented-late-breaking-clinical

Phase 2 Results on AKCEA-APO(a)-LRx Presented in Late ... “These data show that AKCEA-APO(a)-LRx significantly reduces Lp(a) in patients with pre-existing cardiovascular disease due to elevated Lp(a) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7577764/

Pelacarsen for lowering lipoprotein(a) Pelacarsen safely and dose-dependently decreased Lp(a) levels by 35–80% and a Phase 3 trial [Lp(a)HORIZON, NCT04023552] is planned to run from 2020 to 2024.

3. ir.ionis.com ir.ionis.com/news-releases/news-release-details/new-england-journal-medicine-publishes-results-phase-2-study

LRx in Patients with Lp(a)-driven Cardiovascular Disease Patients treated with AKCEA-APO(a)-LRx received pre-specified endpoints for Lp(a) levels with favorable safety and tolerability profile.

4. 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)

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1905239

Lipoprotein(a) Reduction in Persons with Cardiovascular ... In a phase 2a trial, APO(a)-LRx was shown to result in a dose-dependent reduction of 66 to 92% in circulating lipoprotein(a) in participants ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1933287425003228

Pelacarsen: Mechanism of action and Lp(a)-lowering effect Pelacarsen is a second-generation ASO that targets the production of apo(a) and includes chemical modifications such as triantennary N-acetylgalactosamine.

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

8. ir.ionis.com ir.ionis.com/news-releases/news-release-details/akcea-completes-enrollment-phase-2b-study-akcea-apoa-lrx

Akcea Completes Enrollment in Phase 2b Study of ... The results of this study will help us better understand the efficacy and safety profile of AKCEA-APO(a)-LRx, so that this program can advance into a pivotal ...