Olpasiran Trials of Cardiovascular Events And LipoproteiN(a) Reduction - DOSE Finding Study

Study Overview
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Brief Summary
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Evaluate the effect of olpasiran administered subcutaneously (SC) compared with placebo, on percent change from baseline in lipoprotein(a) (Lp[a]).

Official Title
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A Double-blind, Randomized, Placebo-controlled Phase 2 Study to Evaluate Efficacy, Safety, and Tolerability of Olpasiran (AMG 890) in Subjects With Elevated Lipoprotein(a)

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Drug: Olpasiran
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 80 years Lipoprotein (a) > 150 nmol/L Evidence of atherosclerotic cardiovascular disease Exclusion Criteria: Severe renal dysfunction History or clinical evidence of hepatic dysfunction Malignancy within the last 5 years Currently receiving, or less than 3 months at Day 1 since receiving > 200 mg/day Niacin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1 Olpasiran Dose 1<br> | Drug: Olpasiran<br>* Dose 1 Dose 2 Dose 3 Dose 4<br>* Other names: AMG 890;|
| Active Comparator: Arm 2 Olpasiran Dose 2<br> | Drug: Olpasiran<br>* Dose 1 Dose 2 Dose 3 Dose 4<br>* Other names: AMG 890;|
| Active Comparator: Arm 3 Olpasiran Dose 3<br> | Drug: Olpasiran<br>* Dose 1 Dose 2 Dose 3 Dose 4<br>* Other names: AMG 890;|
| Active Comparator: Arm 4 Olpasiran Dose 4<br> | Drug: Olpasiran<br>* Dose 1 Dose 2 Dose 3 Dose 4<br>* Other names: AMG 890;|
| Placebo Comparator: Arm 5 Placebo Dose 5<br> | Drug: Placebo<br>* Dose 5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 36 | Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit. | Baseline and Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Lp(a) at Week 48 | Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit. | Baseline and Week 48 | 
| Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48 | Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit. | Baseline; Week 36 and Week 48 | 
| Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48 | Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit. | Baseline; Week 36 and Week 48 | 
| Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48 | Pharmacokinetic blood draws were collected at one timepoint during the 6-12 and 24-72 hour flexible time windows and at Week 48. Lower limit of quantification (LLOQ) = 0.400 ng/mL. Values below the LLOQ were set to zero. | Pre-dose and 1, 3, 6-12, and 24-72 hours post-dose on Day 1 and Week 24; Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Olpasiran, AMG 890, siRNA, lipoprotein (a) Lp(a), Cardiovascular, Cardiovascular disease, Atherosclerotic cardiovascular disease, Cholesterol, Apolipoprotein (B), Hyperlipidemia, Dyslipidemia