Pelacarsen for Cardiovascular Disease

Recruiting at 107 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

400 Participants Needed

Trial Summary

What is the purpose of this trial?

Study CTQJ230A12303 is a randomized, double-blind placebo-controlled, Phase IIIb study to evaluate the efficacy, safety and tolerability of pelacarsen (TQJ230) 80 mg s.c. QM compared with placebo s.c. QM in US Black/African American and Hispanic participants with established ASCVD and elevated levels of Lp(a) who are treated for cardiovascular (CV) risk factors according to local practice/guidelines for the reduction of cardiovascular risk.

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.

What makes the drug Pelacarsen unique for treating cardiovascular disease?

Pelacarsen is unique because it is a liver-targeted antisense oligonucleotide specifically designed to lower lipoprotein(a) [Lp(a)] levels, which are a genetic risk factor for cardiovascular disease. Unlike other treatments, it directly targets the LPA gene messenger RNA, offering a novel approach to reducing cardiovascular risk in patients with high Lp(a) levels. ^{1 2 3 4 5}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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 a Black/African American or Hispanic person aged 18 to 80 living in the US.

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

Exclusion Criteria

Pregnant or nursing women

My blood pressure is not controlled by medication.

Platelet count <140,000 per mm3

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

Pelacarsen for lowering lipoprotein(a): implications for patients with chronic kidney disease. [2023]

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

Efficacy and safety of pelacarsen in lowering Lp(a) in healthy Japanese subjects. [2023]

4. United States 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. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

A Review of the Clinical Pharmacology of Pelacarsen: A Lipoprotein(a)-Lowering Agent. [2022]