A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Olpasiran in Chinese Participants With Elevated Serum Lipoprotein(a)

• ClinicalTrials.gov Identifier: NCT04987320
• Recruitment Status: Completed
• First Posted: August 3, 2021
• Last Update Posted: September 25, 2023
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Study Description

Brief Summary:

The main objective of this study is to evaluate the pharmacokinetics (PK) of a single dose of Olpasiran in Chinese participants with elevated serum lipoprotein(a) (Lp[a]).

Condition or disease	Intervention/treatment	Phase
Elevated Serum Lipoprotein(a)	Drug: Olpasiran	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: An Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Olpasiran in Chinese Subjects With Elevated Serum Lipoprotein(a)
• Actual Study Start Date: July 28, 2021
• Actual Primary Completion Date: November 12, 2021
• Actual Study Completion Date: March 18, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Olpasiran Dose A; Participants will be administered Olpasiran dose A as a subcutaneous injection.	Drug: Olpasiran; Subcutaneous injection; Other Name: AMG 890
Experimental: Olpasiran Dose B; Participants will be administered Olpasiran dose B as a subcutaneous injection.	Drug: Olpasiran; Subcutaneous injection; Other Name: AMG 890

Outcome Measures

Primary Outcome Measures :

1. Maximum Observed Concentration (Cmax) of Olpasiran [ Time Frame: Day 1 to Day 85 ]
2. Area Under the Concentration-time Curve (AUC) of Olpasiran [ Time Frame: Day 1 to Day 85 ]
3. Time to Maximum Observed Concentration (tmax) [ Time Frame: Day 1 to Day 85 ]
4. Half-life (t1/2) of Olpasiran [ Time Frame: Day 1 to Day 85 ]
5. Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Olpasiran [ Time Frame: Day 1 to Day 85 ]
6. Apparent Total Body Clearance (CL/F) of Olpasiran [ Time Frame: Day 1 to Day 85 ]

Secondary Outcome Measures :

1. Number of Participants with Treatment-emergent Adverse Events [ Time Frame: Day 1 to Day 225 ]
2. Number of Participants with a Clinically Significant Change from Baseline in Clinical Laboratory Tests [ Time Frame: Day 1 to Day 225 ]
3. Number of Participants with a Clinically Significant Change from Baseline in 12-lead Electrocardiograms (ECGs) [ Time Frame: Day 1 to Day 225 ]
4. Number of Participants with a Clinically Significant Change from Baseline in Vital Signs [ Time Frame: Day 1 to Day 225 ]
5. Number of Participants with a Clinically Siginificant Change from Baseline in Lipid Levels [ Time Frame: Day 1 to Day 225 ]
6. Number of Participants with a Clinically Significant Change from Baseline in Serum Lipoprotein(a) (LP[a]) [ Time Frame: Day 1 to Day 225 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Inclusion eligibility criteria will be evaluated in 2 parts during the screening period:

• Part 1: After written informed consent is obtained, subjects will provide a blood sample for a preliminary Lp(a) assessment to determine eligibility for Part 2 screening. Subjects with Lp(a) ≥ 70 nmol/L (or approximately ≥ 27 mg/dL) will be eligible to return to the CRU Part 2 screening. Subjects not eligible to return for Part 2 screening will be screen failed.
• Part 2: Eligible subjects will complete all remaining screening procedures and tests that establish eligibility within 40 days prior to the Day 1 visit.

Part 1:

• Must be a resident in mainland China, Hong Kong, or Taiwan, and of Chinese Ancestry
• Male or female subjects, between 18 and 60 years of age (inclusive) at the time of Screening
• Screening serum Lp(a) ≥ 70 nmol/L (or approximately ≥ 27 mg/dL).

Part 2:

• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [e.g., suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) as assessed by the Investigator (or designee).
• Body mass index between 18 and 32 kg/m^2 (inclusive) at the time of Screening.
• Subjects who are on statin must be on a stable dose of the same statin for at least 6 weeks prior to enrollment, and plan to remain on a stable dose (i.e., no change in medication or dosage) for the duration of the study

• Females must be of non-reproductive potential:

  a. Postmenopausal defined as: i. Age of ≥ 55 years with no menses for at least 12 months; OR ii. Age of < 55 years with no menses for at least 12 months AND with a follicle stimulating hormone (FSH) level > 40 IU/L or according to the definition of "postmenopausal range" for the laboratory involved; OR b. History of hysterectomy; OR c. History of bilateral oophorectomy

Exclusion Criteria:

• History or clinical evidence of peripheral neuropathy
• Currently receiving apheresis as lipid reducing therapy
• History or clinical evidence of bleeding diathesis or any coagulation disorder, including prothrombin time (PT), activated partial thromboplastin time (APTT), or platelet count outside of the laboratory's normal reference range at screening. Subjects with PT and/or APTT values that are outside of the laboratory's normal reference range at screening may still be eligible to proceed to enrollment if the results are judged by the investigator in consultation with the study medical monitor to not be clinically significant.
• History or clinical evidence of diabetes mellitus, including a fasting glucose ≥ 125 mg/dL (6.9 mmol/L) at Screening
• Use of any herbal medicines, vitamins or dietary supplements known to affect lipid metabolism (e.g. sigh oils > 100mg/day, red yeast extract), within 30 days prior to dosing on Day 1 and for the duration of the study

Contacts and Locations

Locations

Hong Kong

Queen Mary Hospital

Hong Kong, HK, Hong Kong

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT04987320
• Other Study ID Numbers: 20190095
• First Posted: August 3, 2021
• Last Update Posted: September 25, 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:

Elevated serum lipoprotein(a); Olpasiran