Assessing the Impact of Lipoprotein (a) Lowering With Pelacarsen (TQJ230) on Major Cardiovascular Events in Patients With CVD (Lp(a)HORIZON)

• ClinicalTrials.gov Identifier: NCT04023552
• Recruitment Status: Active, not recruiting
• First Posted: July 17, 2019
• Last Update Posted: October 10, 2022
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: July 16, 2019
• First Posted Date: July 17, 2019
• Last Update Posted Date: October 10, 2022
• Actual Study Start Date: December 12, 2019
• Estimated Primary Completion Date: May 29, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 15, 2022)

• Time to first occurrence of clinical endpoint committee confirmed expanded major adverse cardiovascular events in patients with elevated Lp(a) ≥ 70 mg/dL [ Time Frame: approximately 4 years ]
  Demonstrate the superiority of pelacarsen (TQJ230) compared to placebo in reducing the risk of expanded MACE (cardiovascular death, non-fatal MI, non-fatal stroke and urgent coronary re-vascularization requiring hospitalization) in the overall study population with established CVD and (Lp(a) ≥ 70 mg/dL)
• Time to the first occurrence of clinical endpoint committee confirmed expanded major adverse cardiovascular events in a population of patients with elevated Lp(a) ≥ 90 mg/dL. [ Time Frame: approximately 4 years ]
  Demonstrate the superiority of pelacarsen (TQJ230) compared to placebo in reducing the risk of expanded MACE (cardiovascular death, non-fatal MI, non-fatal stroke and urgent coronary re-vascularization requiring hospitalization) in the overall study population with established CVD and (Lp(a) ≥ 90 mg/dL)

Original Primary Outcome Measures (submitted: July 16, 2019)

• Time to first occurrence of clinical endpoint committee confirmed expanded major adverse cardiovascular events in patients with elevated Lp(a) ≥ 70 mg/dL [ Time Frame: approximately 4 years ]
  Demonstrate the superiority of TQJ230 compared to placebo in reducing the risk of expanded MACE (cardiovascular death, non-fatal MI, non-fatal stroke and urgent coronary re-vascularization requiring hospitalization) in the overall study population with established CVD and (Lp(a) ≥ 70 mg/dL)
• Time to the first occurrence of clinical endpoint committee confirmed expanded major adverse cardiovascular events in a population of patients with elevated Lp(a) ≥ 90 mg/dL. [ Time Frame: approximately 4 years ]
  Demonstrate the superiority of TQJ230 compared to placebo in reducing the risk of expanded MACE (cardiovascular death, non-fatal MI, non-fatal stroke and urgent coronary re-vascularization requiring hospitalization) in the overall study population with established CVD and (Lp(a) ≥ 90 mg/dL)

Current Secondary Outcome Measures (submitted: March 15, 2022)

• Time to the first occurrence of the clinical endpoint committee confirmed composite endpoint of major adverse cardiovascular events (CV death, non-fatal MI, and non-fatal stroke) [ Time Frame: approximately 4 years ]
  Demonstrate the superiority of pelacarsen (TQJ230) compared to placebo in reducing the risk of the MACE composite of CV death, nonfatal MI and non-fatal stroke.
• Time to the first occurrence of the clinical endpoint committee confirmed composite endpoint of coronary heart disease: coronary heart disease death, non-fatal MI, urgent coronary re-vascularization requiring hospitalization [ Time Frame: approximately 4 years ]
  Demonstrate the superiority of pelacarsen (TQJ230) compared to placebo in reducing the risk of the composite of coronary heart disease (CHD) outcomes: death due to CHD, nonfatal MI and urgent coronary revascularization requiring hospitalization.
• Number of participants with confirmed all-cause death [ Time Frame: approximately 4 years ]
  Evaluation by clinical endpoint committee the rate of all-cause death

Original Secondary Outcome Measures (submitted: July 16, 2019)

• Time to the first occurrence of the clinical endpoint committee confirmed composite endpoint of major adverse cardiovascular events (CV death, non-fatal MI, and non-fatal stroke) [ Time Frame: approximately 4 years ]
  Demonstrate the superiority of TQJ230 compared to placebo in reducing the risk of the MACE composite of CV death, nonfatal MI and non-fatal stroke.
• Time to the first occurrence of the clinical endpoint committee confirmed composite endpoint of coronary heart disease: coronary heart disease death, non-fatal MI, urgent coronary re-vascularization requiring hospitalization [ Time Frame: approximately 4 years ]
  Demonstrate the superiority of TQJ230 compared to placebo in reducing the risk of the composite of coronary heart disease (CHD) outcomes: death due to CHD, nonfatal MI and urgent coronary revascularization requiring hospitalization.
• Number of participants with confirmed all-cause death [ Time Frame: approximately 4 years ]
  Evaluation by clinical endpoint committee the rate of all-cause death

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Assessing the Impact of Lipoprotein (a) Lowering With Pelacarsen (TQJ230) on Major Cardiovascular Events in Patients With CVD
• Official Title: A Randomized Double-blind, Placebo-controlled, Multicenter Trial Assessing the Impact of Lipoprotein (a) Lowering With Pelacarsen (TQJ230) on Major Cardiovascular Events in Patients With Established Cardiovascular Disease
• Brief Summary: 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)
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Cardiovascular Disease and Lipoprotein(a)

Intervention

• Drug: TQJ230
  TQJ230 80 mg injected monthly administered subcutaneously
• Drug: Placebo
  Placebo to match TQJ230 prefilled syringe to be injected subcutaneously
  Other Name: Placebo to match TQJ230

Study Arms

• Experimental: TQJ230
  TQJ230 80 mg injected monthly administered subcutaneously
  Intervention: Drug: TQJ230
• Placebo Comparator: Placebo
  Monthly subcutaneous injections.
  Intervention: Drug: Placebo

Publications *

• Tsimikas S, Reeves RR, Patel MP. Always Present, But Now Rediscovered: Lp(a) as a Predictor of Long-Term Outcomes in PCI. JACC Cardiovasc Interv. 2021 Sep 27;14(18):2069-2072. doi: 10.1016/j.jcin.2021.08.032. No abstract available.
• Plakogiannis R, Sorbera M, Fischetti B, Chen M. The Role of Antisense Therapies Targeting Lipoprotein(a). J Cardiovasc Pharmacol. 2021 Jul 1;78(1):e5-e11. doi: 10.1097/FJC.0000000000001045.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 7, 2022): 8324
• Original Estimated Enrollment (submitted: July 16, 2019): 7680
• Estimated Study Completion Date: May 30, 2025
• Estimated Primary Completion Date: May 29, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria

• Lp(a) ≥ 70 mg/dL at the screening visit, measured at the Central laboratory
• Myocardial infarction: ≥ 3 months from screening and randomization to ≤ 10 years prior to the screening visit
• Ischemic stroke: ≥ 3 months from screening and randomization to ≤ 10 years prior to the screening visit
• Clinically significant symptomatic peripheral artery disease

Key Exclusion Criteria

• Uncontrolled hypertension
• Heart failure New York Heart Association (NYHA) class IV
• History of malignancy of any organ system
• History of hemorrhagic stroke or other major bleeding
• Platelet count ≤LLN
• Active liver disease or hepatic dysfunction
• Significant kidney disease
• Pregnant or nursing women

Other protocol-defined inclusion/exclusion criteria may apply at the end.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, Denmark, France, Germany, Greece, Guatemala, Hong Kong, Hungary, Iceland, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Norway, Peru, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, United States
• Removed Location Countries: Philippines

Administrative Information

• NCT Number: NCT04023552
• Other Study ID Numbers: CTQJ230A12301; CTQJ230A12301 ( Other Identifier: Novartis ); 2019-001076-11 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient -level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with the applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: October 2022