Atherosclerotic Cardiovascular Disease (ASCVD)
Conditions
Keywords
Lipoprotein(a), cardiovascular disease, ASCVD, pelacarsen (TQJ230)
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.
Interventions
DRUGPelacarsen
Pelacarsen will be provided as solution for injection in prefilled syringe 80 mg for subcutaneous injection.
DRUGPlacebo
Placebo will be provided as solution for injection in prefilled syringe for subcutaneous injection.
DRUGInclisiran
All participants will be administered two loading doses of inclisiran as background treatment at Run-in 1 and Run-in 2, separated by 3 months, according to the approved label. After that inclisiran will be administered every 6 months, i.e., Month 5 and Month 11.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key 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 Key
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in log transformed lipoprotein A (Lp(a)) concentration | 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
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving reduction in Lp(a) levels at Month 6 | Baseline, Month 6 | Efficacy of pelacarsen versus placebo in reducing Lp(a) |
| Incidence of treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs) | 16 Months | The TEAEs will be defined as any recorded AE with start date located in the on-treatment period. To understand the effect of pelacarsen versus placebo on safety and tolerability in participants treated with background inclisiran. Incidence and severity of AEs by treatment group, including changes in the vital signs, electrocardiogram and laboratory results qualifying and reported as AEs. |
| Incidence of treatment emergent adverse events of special interest (AESI) | 12 Months | To understand the effect of pelacarsen versus placebo on safety and tolerability in participants treated with background inclisiran |
| Incidence of study and treatment discontinuations due to TEAEs | 12 Months | Incidence proportion of study discontinuations due to TEAEs |
Countries
China, France, Germany, Hong Kong, Italy, Netherlands, Puerto Rico, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed