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

Novartis Pharmaceuticals51 enrolled

Overview

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.

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) investigated 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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Hyperlipoproteinemia(a)

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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) * Clinically significant symptomatic coronary 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

Locations (13)

Novartis Investigative Site

Villingen-Schwenningen, Baden-Wurttemberg, Germany

Novartis Investigative Site

Munich, Bavaria, Germany

Novartis Investigative Site

Würzburg, Bavaria, Germany

Novartis Investigative Site

Frankfurt am Main, Hesse, Germany

Novartis Investigative Site

Göttingen, Lower Saxony, Germany

Novartis Investigative Site

Düsseldorf, North Rhine-Westphalia, Germany

Novartis Investigative Site

Geilenkirchen, North Rhine-Westphalia, Germany

Novartis Investigative Site

Dresden, Saxony, Germany

Novartis Investigative Site

Berlin, Germany

Novartis Investigative Site

Cloppenburg, Germany

...and 3 more locations

Outcomes

Primary Outcomes

Rate of Lipoprotein Apheresis Sessions Performed Over 52 Weeks Normalized to the Weekly Lipoprotein Apheresis Schedule

Rate (proportion) of apheresis sessions was calculated as the number of actual lipoprotein apheresis (LA) sessions received, divided by the number of planned LA sessions during the 52-week period, which is 52 for patients who completed all study visits, or pro-rated for those who discontinued early. This rate could range from 0 to 1, with 0 indicating that the patient had skipped all planned LA sessions, and 1 indicating that the patient had received all planned sessions. Multiple imputation for missing Lp(a) data was performed, and missing apheresis data was imputed.

Time frame: Up to Week 52

Secondary Outcomes

Time to Lipoprotein Apheresis Avoidance

Lipoprotein apheresis avoidance is defined as at least 24 consecutive weeks of no lipoprotein apheresis until end of study.

Time frame: From randomization up to Week 52

Number of Participants With Total Lipoprotein Apheresis Avoidance From Week 12 to Week 52

Total lipoprotein apheresis avoidance is defined as no apheresis performed from Week 12 to Week 52.

Time frame: Week 12 up to Week 52

Change From Baseline to Week 52 in the Log-transformed Lp(a) Reported as mg/dL

Week 52 / Baseline ratio in Lp(a) of pelacarsen (TQJ230) vs placebo reported as particle mass (mg/dL). Baseline Lp(a) was defined as the last non-missing pre-lipoprotein apheresis assessment prior to the first dose of randomized study drug.

Time frame: Baseline, week 52

Change From Baseline to Week 52 in the Log-transformed Lp(a) Reported as Nmol/L

Week 52 / Baseline ratio in Lp(a) of pelacarsen (TQJ230) vs placebo reported as molar concentration (nmol/L). Baseline Lp(a) was defined as the last non-missing pre-lipoprotein apheresis assessment prior to the first dose of randomized study drug.

Time frame: Baseline, week 52