A Multicenter Trial Assessing the Impact of Lipoprotein(a) Lowering With Pelacarsen (TQJ230) on the Rate of Weekly Lipoprotein Apheresis Sessions in Patients With Hyperlipoproteinemia(a) and Established Cardiovascular Disease in Germany

A Randomized, Double-blind, Placebo-controlled, Multicenter Trial Assessing the Reduction of the Rate of Lipoprotein Apheresis After Treatment With Pelacarsen (TQJ230) Compared to Placebo in Patients With Hyperlipoproteinemia(a) and Established Cardiovascular Disease Undergoing Weekly Lipoprotein Apheresis in Germany

Phase III study to test the hypothesis that treatment with pelacarsen (TQJ230) 80 mg Q4W compared to placebo significantly reduces the rate of lipoprotein apheresis in patients with hyperlipoproteinemia (a) and established cardiovascular disease currently undergoing lipoprotein apheresis in Germany on a weekly schedule.

Study Overview

• Status: Active, not recruiting
• Conditions: Hyperlipoproteinemia(a)
• Intervention / Treatment: Drug: Pelacarsen (TQJ230) 80 mg s.c.; Drug: Corresponding Placebo

Detailed Description

Lipoprotein apheresis to date is the only approved therapeutic option for cardiovascular (CV) risk reduction in patients with severely elevated Lp(a) levels in Germany. Lipoprotein apheresis is an expensive, burdensome, and time-consuming procedure. The current study (CTQJ230A12302) will investigate if treatment with pelacarsen (TQJ230) 80 mg Q4W vs placebo reduces the rate of lipoprotein apheresis in patients with hyperlipoproteinemia(a) and established CV disease

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Cloppenburg, Germany, 49661
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Frankfurt, Germany, 60431
    • Novartis Investigative Site
  • Gottingen, Germany, 37075
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Muenchen, Germany, 81377
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Villingen-Schwenningen, Germany, D78052
    • Novartis Investigative Site
  • Wuerzburg, Germany, 97080
    • Novartis Investigative Site
  • North Rhine-Westphalia
    • Duesseldorf, North Rhine-Westphalia, Germany, 42010
      • Novartis Investigative Site
    • Geilenkirchen, North Rhine-Westphalia, Germany, 52511
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients currently undergoing lipoprotein apheresis for isolated Lp(a) on a weekly schedule in Germany for ≥ 12 months prior to screening with at least 40 sessions within the past 52 weeks prior to randomization
• Lipoprotein(a) (Lp(a))> 60 mg/dL at screening
• Spontaneous prior myocardial infarction (MI): ≥ 3 months from screening visit to ≤ 10 years prior to the screening visit, and/or
• Ischemic stroke: ≥ 3 months from screening visit to ≤ 10 years prior to the screening visit, and/or
• Clinically significant symptomatic peripheral artery disease (PAD)

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 <140,000 per mm3 at screening
• Active liver disease or hepatic dysfunction
• Significant kidney disease
• Pregnant or nursing women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Corresponding Placebo; Placebo to Pelacarsen; Other Names: Placebo
Experimental: Pelacarsen (TQJ230)	Drug: Pelacarsen (TQJ230) 80 mg s.c.; Pelacarsen (TQJ230) 80 mg s.c. Q4W; Other Names: TQJ230

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of lipoprotein apheresis sessions performed over 52 weeks normalized to the weekly lipoprotein apheresis schedule	Demonstrate superiority of pelacarsen (TQJ230) compared to placebo in reducing the rate of lipoprotein apheresis sessions in patients with hyperlipoproteinemia(a) and established CVD during 52 weeks of treatment	Over 52 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to lipoprotein apheresis avoidance (where lipoprotein apheresis avoidance is defined as at least 24 weeks of no lipoprotein apheresis until end of study)	Demonstrate superiority of pelacarsen (TQJ230) compared to placebo in reducing the time to lipoprotein apheresis avoidance	At least 24 weeks up to Week 52
Total avoidance of lipoprotein apheresis from week 12 to week 52	Demonstrate superiority of pelacarsen (TQJ230) vs placebo in avoiding the performance of any lipoprotein apheresis in the last 40 weeks of the study	Week 12 to Week 52
Change from baseline to week 52 in the log-transformed Lp(a) (measured prior to planned lipoprotein apheresis)	Demonstrate superiority of pelacarsen (TQJ230) vs placebo in lowering Lp(a) after 52 weeks	52 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of lipoprotein apheresis sessions from week 12 to week 52 and week 24 to week 52 normalized to the weekly lipoprotein apheresis schedule	Evaluate rate of lipoprotein apheresis at defined periods of time	Week 12 to 52, Week 24 to 52
Total avoidance of lipoprotein apheresis between week 24 to week 52	Evaluate avoidance of the performance of any lipoprotein apheresis in the last 28 weeks of the study	Week 24 to Week 52
Time-averaged Lp(a) levels	Evaluate pre- and post-lipoprotein apheresis Lp(a) levels	52 weeks
Percent change in total cholesterol, LDL-C, High-density lipoprotein-Cholesterol (HDL-C), non-HDL-C, Very-low-density lipoprotein-Cholesterol (VLDL-C), apoB and triglycerides (pre- lipoprotein apheresis) from baseline to week 52	Evaluate the change in expanded lipid profile parameters	52 weeks
Change from baseline to week 52 in the physical and mental health summary scores for the SF-36 questionnaire and a patient preference questionnaire	Evaluate quality of life	52 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2022
• Primary Completion (Estimated): June 27, 2025
• Study Completion (Estimated): June 27, 2025

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: March 22, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: cardiovascular disease; apheresis; TQJ230; Lipoprotein (a); pelacarsen
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Cardiovascular Diseases; Hyperlipidemias; Hyperlipoproteinemias
• Other Study ID Numbers: CTQJ230A12302; 2021-003059-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No