Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a)

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a)

This is a first-in-human, randomized, double-blind, placebo-controlled, single ascending dose study in subjects with elevated plasma Lipoprotein(a) [Lp(a)]. AMG 890 will be evaluated in approximately 80 subjects to assess safety, tolerability, pharmacokinetics and pharmacodynamic effects.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease
• Intervention / Treatment: Drug: Placebo; Drug: AMG 890

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Clinical Medical and Analytical eXellence CMAX
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research Limited
• United States
  • California
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • South Miami, Florida, United States, 33143
      • QPS Miami Research Associates
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • New York
    • New York, New York, United States, 10016
      • New York University
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Medpace Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Men and women with ages between 18 and 70 years old, inclusive.
• Protocol-defined elevated plasma Lp(a) level.
• Body mass index (BMI) greater than or equal to 18 and less than or equal to 40 kg/m2, at screening.
• Women must be of non-reproductive potential.
• Other Inclusion criteria may apply

Exclusion Criteria:

• Currently receiving treatment in another investigational device or drug study.
• Women who are lactating/breastfeeding or who plan to breastfeed while on study or through 90 days after receiving the last dose of investigational product (for subjects who withdraw prior to end of study).
• History or evidence of a clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
• History or clinical evidence of bleeding diathesis or any coagulation disorder.
• History or clinical evidence of peripheral neuropathy.
• Other Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Single Ascending Dose Cohorts	Drug: Placebo; Calculated volume to match experimental drug.
Experimental: AMG 890; Single Ascending Dose Cohorts	Drug: AMG 890; Ascending Single Doses of AMG 890

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subject incidence of treatment-emergent adverse events		up to 365 days
Changes in blood pressure	The analysis will include summary statistics at selected time points by treatment group.	Up to 365 days
Changes in heart rate	The analysis will include summary statistics at selected time points by treatment group	Up to 365 days
Changes in respiratory rate	The analysis will include summary statistics at selected time points by treatment group.	Up to 365 days
Changes in temperature	The analysis will include summary statistics at selected time points by treatment group.	Up to 365 days
Changes in QRS interval	The analysis will include summary statistics at selected time points by treatment group.	Up to 365 days
Changes in PR interval	The analysis will include summary statistics at selected time points by treatment group	Up to 365 days
Changes in QT interval	The analysis will include summary statistics at selected time points by treatment group.	Up to 365 days
Changes in RR interval	The analysis will include summary statistics at selected time points by treatment group	Up to 365 days
Changes in red blood cells	The analysis will include summary statistics at selected time points by treatment group	Up to 365 days
Changes in platelets	The analysis will include summary statistics at selected time points by treatment group	Up to 365 days
Changes in white blood cells	The analysis will include summary statistics at selected time points by treatment group	Up to 365 days
Changes in prothrombin time (PT)		Up to 365 days
Changes in international normalized ratio (INR)		Up to 365 days
Changes in activated partial thromboplastin time (aPTT)		Up to 365 days
Changes in Thrombin time (TT)		Up to 365 days
Changes in aspartate aminotransferase (AST) levels (units: U/L)	The analysis will include summary statistics at selected time points by treatment group	Up to 365 days
Changes in alanine aminotransferase (ALT) levels (units: U/L)	The analysis will include summary statistics at selected time points by treatment group	Up to 365 days
Changes in total bilirubin levels (units: μmol/L)	The analysis will include summary statistics at selected time points by treatment group	Up to 365 days
Changes in direct bilirubin levels (units: μmol/L)	The analysis will include summary statistics at selected time points by treatment group	Up to 365 days
Changes in alkaline phosphatase levels (units: U/L)	The analysis will include summary statistics at selected time points by treatment group	Up to 365 days
Changes in total protein levels (units: g/L)	The analysis will include summary statistics at selected time points by treatment group	Up to 365 days
Changes in albumin levels (units: g/L)	The analysis will include summary statistics at selected time points by treatment group	Up to 365 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics parameter of maximum observed concentration (Cmax)	up to 365 days
Pharmacokinetics parameter of time of maximum observed concentration (tmax)	up to 365 days
Pharmacokinetics parameter of area under the concentration time curve (AUC)	up to 365 days
Change in plasma Lp(a) over time	Up to 365 days
Percent change in plasma Lp(a) over time	Up to 365 days

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• Koren MJ, Moriarty PM, Baum SJ, Neutel J, Hernandez-Illas M, Weintraub HS, Florio M, Kassahun H, Melquist S, Varrieur T, Haldar SM, Sohn W, Wang H, Elliott-Davey M, Rock BM, Pei T, Homann O, Hellawell J, Watts GF. Preclinical development and phase 1 trial of a novel siRNA targeting lipoprotein(a). Nat Med. 2022 Jan;28(1):96-103. doi: 10.1038/s41591-021-01634-w. Epub 2022 Jan 13.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2018
• Primary Completion (Actual): April 18, 2023
• Study Completion (Actual): April 18, 2023

Study Registration Dates

• First Submitted: June 19, 2018
• First Submitted That Met QC Criteria: August 9, 2018
• First Posted (Actual): August 13, 2018

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: 20170544

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No