A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Pelacarsen (TQJ230) With Background Inclisiran in Participants With Atherosclerotic Cardiovascular Disease (ASCVD), and Elevated LDL-C and Lp(a)
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 340
- Locations
- 124
- Primary Endpoint
- Change in log transformed lipoprotein A (Lp(a)) concentration
Study Overview
Brief Summary
The purpose of the study CTQJ230A12304, is to evaluate the efficacy, safety, and tolerability of pelacarsen (TQJ230) compared to placebo in participants with ASCVD who have elevated lipoprotein(a) (Lp(a)), and who are on background inclisiran treatment for elevated low-density lipoprotein cholesterol (LDL-C).
Detailed Description
This is a randomized, double-blind, placebo-controlled, multicenter, parallel group study followed by an open-label treatment period.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male and female participants 18 to ≤80 years of age at Screening visit
- •Established ASCVD, defined as documented coronary heart disease (CHD), cerebrovascular disease (CVD), or peripheral arterial disease (PAD) at Screening visit
- •On stable dose of local guideline recommended lipid lowering therapy for at least 30 days prior to Screening visit
- •Participants must successfully complete the run-in period of background inclisiran treatment in order to be randomized
- •On standard of care (SoC) treatment for other CVD risk factors including hypertension and diabetes for at least 30 days prior to Randomization/Baseline visit
- •Central laboratory reported Lp(a) ≥175 nmol/L at Screening visit
- •Central laboratory reported LDL-C >70 mg/dL (or >1.8 mmol/L) at Screening visit
Exclusion Criteria
- •Prior treatment with inclisiran
- •Any other PCSK9 inhibitor (e.g., evolocumab, alirocumab) use within 4 months prior to Screening visit
- •Uncontrolled hypertension at Randomization/Baseline visit
- •Heart failure New York Heart Association (NYHA) class IV at Screening visit or at Randomization/Baseline visit (Day 1)
- •Triglycerides ≥400 mg/dL at Screening visit
- •History of malignancy of any organ system within the past 5 years
- •Myocardial infarction, stroke or other major bleeding, coronary or lower limb re vascularization, major cardiac or non-cardiac surgery between Screening visit and Randomization/Baseline visit (Day 1)
- •Central laboratory reported platelet count <140,000 per mm3
- •Active liver disease or hepatic dysfunction at Screening visit
- •Significant kidney disease at Screening visit
- •Pregnant or nursing women at Screening visit
- •Any uncontrolled chronic or serious medical condition which may pose an immediate risk to clinical stability of the study participant at Screening visit
- •Other protocol-defined inclusion/exclusion criteria may apply.
Arms & Interventions
Pelacarsen
Participants randomized in Pelacarsen arm, will be administered pelacarsen (TQJ230) subcutaneous injection once monthly for 12 months.
Intervention: Inclisiran (Drug)
Placebo
Participants will be administered placebo subcutaneous injection once monthly for 6 months. After Month 6, all participants will receive pelacarsen 80 mg injection for the remaining 6 months during the open-label treatment period.
Intervention: Placebo (Drug)
Pelacarsen
Participants randomized in Pelacarsen arm, will be administered pelacarsen (TQJ230) subcutaneous injection once monthly for 12 months.
Intervention: Pelacarsen (Drug)
Placebo
Participants will be administered placebo subcutaneous injection once monthly for 6 months. After Month 6, all participants will receive pelacarsen 80 mg injection for the remaining 6 months during the open-label treatment period.
Intervention: Pelacarsen (Drug)
Placebo
Participants will be administered placebo subcutaneous injection once monthly for 6 months. After Month 6, all participants will receive pelacarsen 80 mg injection for the remaining 6 months during the open-label treatment period.
Intervention: Inclisiran (Drug)
Outcomes
Primary Outcomes
Change in log transformed lipoprotein A (Lp(a)) concentration
Time Frame: Baseline, 6 Months
To evaluate the efficacy of Pelacarsen compared to placebo, in reducing Lp(a) levels at Month 6 in ASCVD participants who have elevated Lp(a), and who are on background inclisiran for elevated LDL-C
Secondary Outcomes
- Proportion of participants achieving reduction in Lp(a) levels at Month 6(Baseline, Month 6)
- Incidence of treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs)(16 Months)
- Incidence of treatment emergent adverse events of special interest (AESI)(12 Months)
- Incidence of study and treatment discontinuations due to TEAEs(12 Months)