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

• ClinicalTrials.gov Identifier: NCT05481411
• Recruitment Status: Completed
• First Posted: August 1, 2022
• Last Update Posted: September 22, 2023
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hepatic Impairment	Drug: Olpasiran	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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
• Actual Study Start Date: September 13, 2022
• Actual Primary Completion Date: April 5, 2023
• Actual Study Completion Date: May 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Single Dose Olpasiran Hepatic Impairment; 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; Subcutaneous injection; Other Name: AMG 890
Experimental: Single Dose Olpasiran Normal Hepatic Function; Participants with normal hepatic function will be enrolled and will receive a single dose of olpasiran on Day 1.	Drug: Olpasiran; Subcutaneous injection; Other Name: AMG 890

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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).

Contacts and Locations

Locations

United States, California

Inland Empire Clinical Trials, LLC

Rialto, California, United States, 92377

United States, Florida

Orlando Clinical Research Center

Orlando, Florida, United States, 32809

United States, Texas

The Texas Liver Institute, Inc.

San Antonio, Texas, United States, 78215

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT05481411
• Other Study ID Numbers: 20220009
• First Posted: August 1, 2022
• Last Update Posted: September 22, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• URL: http://www.amgen.com/datasharing

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Amgen:

Olpasiran; Hepatic Impairment; Normal Hepatic Function; AMG 890

Additional relevant MeSH terms:

Liver Diseases; Digestive System Diseases