Hyperlipoproteinemia(a)
Conditions
Keywords
Lipoprotein (a), cardiovascular disease, apheresis, TQJ230, pelacarsen
Brief summary
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.
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) 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
Interventions
DRUGPelacarsen (TQJ230) 80 mg s.c.
Pelacarsen (TQJ230) 80 mg s.c. Q4W
DRUGCorresponding Placebo
Placebo to Pelacarsen
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Lipoprotein Apheresis Sessions Performed Over 52 Weeks Normalized to the Weekly Lipoprotein Apheresis Schedule | Up to Week 52 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Lipoprotein Apheresis Avoidance | From randomization up to Week 52 | Lipoprotein apheresis avoidance is defined as at least 24 consecutive weeks of no lipoprotein apheresis until end of study. |
| Number of Participants With Total Lipoprotein Apheresis Avoidance From Week 12 to Week 52 | Week 12 up to Week 52 | Total lipoprotein apheresis avoidance is defined as no apheresis performed from Week 12 to Week 52. |
| Change From Baseline to Week 52 in the Log-transformed Lp(a) Reported as mg/dL | Baseline, week 52 | 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. |
| Change From Baseline to Week 52 in the Log-transformed Lp(a) Reported as Nmol/L | Baseline, week 52 | 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. |
Countries
Germany
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Participant flow
Recruitment details
A total of 51 participants were recruited in 13 centers across Germany
Pre-assignment details
60 participants were screened and 51 randomized. There was a 14 day screening period before treatment at baseline.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 21 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants |
| Age, Continuous | 62.0 years STANDARD_DEVIATION 8.1 |
| Participants with prior clinically significant symptomatic coronary artery disease | 1 Participants |
| Participants with prior ischemic stroke | 6 Participants |
| Participants with prior miocardial infarction | 21 Participants |
| Participants with prior peripheral artery disease | 10 Participants |
| Qualifying events Prior clinically significant symptomatic CAD only | 1 Participants |
| Qualifying events Prior ischemic stroke only | 2 Participants |
| Qualifying events Prior myocardial infarction only | 0 Participants |
| Qualifying events Prior peripheral artery disease only | 2 Participants |
| Qualifying events Subjects with more than one qualifying event | 24 Participants |
| Race/Ethnicity, Customized Ethnicity Not hispanic or latino | 26 Participants |
| Race/Ethnicity, Customized Race White | 51 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 1 / 25 | 1 / 51 |
| other Total, other adverse events | 23 / 26 | 17 / 25 | 40 / 51 |
| serious Total, serious adverse events | 7 / 26 | 6 / 25 | 13 / 51 |
Outcome results
None listed