A Study to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of Olpasiran in Participants With Various Degrees of Hepatic Impairment

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the pharmacokinetics (PK) of a single dose of olpasiran in participants with mild, moderate, or severe hepatic impairment compared to participants with normal hepatic function.

Official Title
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A Phase I, Open-label Single Dose Study to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of Olpasiran in Subjects With Various Degrees of Hepatic Impairment

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: Olpasiran


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants of nonchildbearing potential, between 18 and 75 years of age (inclusive) at the time of Screening. Body mass index between 18.0 and 40.0 kg/m^2 (inclusive) at the time of Screening. Participants with Normal Hepatic Function Only: • In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations at Screening and Check-in as assessed by the Investigator (or designee). Participants with Hepatic Impairment Only: • Child-Pugh A (Group 2), B (Group 3), or C (Group 4) classification defined by both Screening (to determine participant group) and Check-in (to confirm participant group prior to dosing) clinical laboratory values and physical examination findings. Exclusion Criteria: History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee). Estimated glomerular filtration rate < 60 mL/min/1.73m^2 (Groups 1-3) or < 50 mL/min/1.73m^2 (Group 4 only) by Modification of Diet in Renal Disease formula at Screening or Check-in. Receiving or has received any investigational drug within the 30 days or 5 half-lives (whichever is longer) before receiving olpasiran. Participants who were previously exposed to olpasiran. Female participants with a positive pregnancy test at Screening or Check-in. Participants with Normal Hepatic Function Only: Positive hepatitis panel. Participants whose results are compatible with prior immunization may be included. Alanine aminotransferase and aspartate aminotransferase elevations > 3x upper limit of normal at Screening or Check-in. Participants with Hepatic Impairment Only: Positive for hepatitis B surface antigen. Participants with positive hepatitis B core antibody may be included if hepatitis B surface antigen is negative. Participants with positive hepatitis B surface antibody may be included (consistent with prior vaccination). Active malignancy of any type. Participants with a history of malignancy that has been eradicated with supporting medical documentation indicating that there is no residual malignancy detected in the past 2 years will be allowed. Values outside the normal range for liver function tests that are not consistent with their hepatic condition, as determined by the Investigator (or designee).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Dose Olpasiran Hepatic Impairment<br>Participants will be enrolled in 1 of 3 hepatic impairment groups based on their hepatic impairment status, as determined by Child-Pugh classification. All participants will receive a single dose of olpasiran on Day 1. | Drug: Olpasiran<br>* Subcutaneous injection<br>* Other names: AMG 890;|
| Experimental: Single Dose Olpasiran Normal Hepatic Function<br>Participants with normal hepatic function will be enrolled and will receive a single dose of olpasiran on Day 1. | Drug: Olpasiran<br>* Subcutaneous injection<br>* Other names: AMG 890;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Serum Concentration (Cmax) of Olpasiran |  | Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29 | 
| Area Under the Plasma Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of Olpasiran |  | Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29 | 
| Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Olpasiran |  | Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Effect Time Curve (AUEC) of Plasma Lipoprotein a (Lp[a]) |  | Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85 | 
| Maximum Inhibitory Effect (Imax) of Plasma Lp(a) |  | Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85 | 
| Time to Reach Imax of Lp(a) |  | Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85 | 
| Number of Participants Who Experience an Adverse Event (AE) |  | Up to Day 85 | 
| Number of Participants with Clinically Significant Changes in Clinical Laboratory Evaluations |  | Up to Day 85 | 
| Number of Participants With Clinically Significant Changes 12-lead Electrocardiogram (ECG) Measurements |  | Up to Day 85 | 
| Number of Participants with Clinically Significant Changes in Vital Signs |  | Up to Day 85 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Olpasiran, Hepatic Impairment, Normal Hepatic Function, AMG 890