Study of Efavaleukin Alfa in Healthy Chinese, Japanese, and Caucasian Participants

A Phase 1, Open-label, Sequential-group, Single-dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of AMG 592 Administered Subcutaneously in Healthy Chinese, Japanese, and Caucasian Subjects

The primary objective of this study is to evaluate the pharmacokinetics (PK) of efavaleukin alfa after single subcutaneous (SC) administration in healthy Chinese, Japanese, and Caucasian participants.

Study Overview

• Status: Completed
• Conditions: Inflammatory Diseases
• Intervention / Treatment: Drug: Efavaleukin alfa

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • LDS
    • Leeds, LDS, United Kingdom, LS2 9LH
      • Labcorp Clinical Research Unit - Leeds

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy male or female participants, between 18 and 55 years of age (inclusive) at the time of Screening.

• Chinese, Japanese, or Caucasian participant:

  • Chinese participants must be of Chinese ancestry (4 grandparents and biological parents).
  • Japanese participants must be first- or second-generation Japanese (4 grandparents and biological parents; participant or both of their parents must have been born in Japan).
  • Caucasian participants are those who self-identify exclusively as such on the electronic case report form (eCRF) and also identify their biological parents as such.
• In good health, determined by no clinically significant findings from medical history, physical examinations, 12-lead electrocardiogram (ECG), vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [eg, 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 17 and 30 kg/m^2 (inclusive) at the time of Screening.

Exclusion Criteria:

• Evidence of scars, tattoos, or other skin lesions that may interfere with the injection site or injection site assessments.
• History or evidence of clinically significant arrhythmia at Screening, including any clinically significant findings on the ECG taken at Check-in.
• A QT interval corrected for heart rate using Fridericia's method (QTcF) interval > 450 msec in male participants or > 470 msec in female participants or history/evidence of long QT syndrome, at Screening or Check-in.
• PR interval > 210 msec, at Screening or Check-in.
• Second- or third-degree atrioventricular (AV) block , at Screening or Check-in.
• Systolic blood pressure (BP) > 140 mmHg or < 90 mmHg, or diastolic BP > 90 mmHg, or HR > 100 bpm, at Screening or Check-in.
• Estimated glomerular filtration rate less than 60 mL/min/1.73 m^2 as calculated by the Modification of Diet in Renal Disease equation, at Screening.
• HbA1C ≥ 7%, at Screening or Check-in.
• Participants who have received live vaccines within 5 weeks prior to Screening, or plan to receive live vaccines within 105 days after administration of an investigational product.
• Positive hepatitis B or hepatitis C panel (ie, positive hepatitis B surface antigen, hepatitis B core antibody or hepatitis C antibody) at Screening, or a medical history for hepatitis B or C; and/or positive human immunodeficiency virus test, at Screening. Participants whose results are compatible with prior vaccination may be included. Participants with a history of hepatitis B vaccination without a history of hepatitis B or C are allowed to participate.
• Consumption of foods and beverages containing poppy seeds within 7 days prior to Check-in.
• History of alcoholism or drug/chemical abuse within 1 year prior to Check-in.
• Use of tobacco- or nicotine-containing products within 6 months prior to Check-in.
• Positive test for illicit drugs, cotinine (tobacco or nicotine use), and/or alcohol use at Screening or Check-in.
• Female participants with a positive pregnancy test at Screening or Check-in.
• Participant has received a dose of an investigational drug within the past 90 days or 5 half-lives of the drug, whichever is longer, prior to Check-in.
• Donation of blood from 90 days prior to Check-in, plasma from 2 weeks prior to Check-in, or platelets from 6 weeks prior to Check-in.
• Participants with abnormal laboratory results for alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (ie, > upper limit of normal) and total bilirubin (ie, > upper limit of normal) at Screening and Check-in.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Chinese participants - efavaleukin alfa dose level 1; Chinese participants will receive a single dose of efavaleukin alfa at dose level 1.	Drug: Efavaleukin alfa; Administered as a single dose SC injection.
Experimental: Group 2: Chinese participants - efavaleukin alfa dose level 2; Chinese participants will receive a single dose of efavaleukin alfa at dose level 2.	Drug: Efavaleukin alfa; Administered as a single dose SC injection.
Experimental: Group 3: Japanese participants - efavaleukin alfa dose level 2; Japanese participants will receive a single dose of efavaleukin alfa at dose level 2.	Drug: Efavaleukin alfa; Administered as a single dose SC injection.
Experimental: Group 4: Caucasian participants - efavaleukin alfa dose level 2; Caucasian participants will receive a single dose of efavaleukin alfa at dose level 2.	Drug: Efavaleukin alfa; Administered as a single dose SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Serum Concentration (Cmax) of Efavaleukin Alfa	Blood samples were collected to determine PK parameters.	Day 1: Pre-dose, 6, 12, & 16 hours post-dose, and days 2 (24 hours post-dose), 3, 4, 5, 6, 8, 11, 15, 22, 29 and 43
Time of the Maximum Observed Serum Concentration (Tmax) of Efavaleukin Alfa	Blood samples were collected to determine PK parameters.	Day 1: Pre-dose, 6, 12, & 16 hours post-dose, and days 2 (24 hours post-dose), 3, 4, 5, 6, 8, 11, 15, 22, 29 and 43
Area Under the Serum Concentration Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Efavaleukin Alfa	Blood samples were collected to determine PK parameters.	Day 1: Pre-dose, 6, 12, & 16 hours post-dose, and days 2 (24 hours post-dose), 3, 4, 5, 6, 8, 11, 15, 22, 29 and 43
Area Under the Serum Concentration Time Curve From Time Zero to Infinity (AUCinf) of Efavaleukin Alfa	Blood samples were collected to determine PK parameters.	Day 1: Pre-dose, 6, 12, & 16 hours post-dose, and days 2 (24 hours post-dose), 3, 4, 5, 6, 8, 11, 15, 22, 29 and 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs)	Adverse events (AEs) were defined as any untoward medical occurrence in clinical study participant irrespective of a causal relationship with the study treatment. TEAEs were any event that occurred after the participant had received study treatment. Any clinically significant changes in physical examinations, clinical laboratory tests and vital signs were recorded as TEAEs. Serious AEs (SAEs) were defined as any event that met at least 1 of the following serious criteria: Resulted in death (fatal); Required in-patient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity; A congenital anomaly/birth defect; Other medically important serious event	Day 1 to Day 43
Number of Participants With Anti-Efavaleukin Alfa Antibodies and Anti-Interleukin 2 (IL-2) Antibodies	Number of participants who tested positive for developing anti-efavaleukin alfa antibodies and/or anti-IL2 antibodies at 1 or more post-baseline time points, who had a negative or no result at baseline.	Day 1 up to Day 43

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2021
• Primary Completion (Actual): October 3, 2022
• Study Completion (Actual): October 3, 2022

Study Registration Dates

• First Submitted: July 26, 2021
• First Submitted That Met QC Criteria: July 26, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Ulcerative colitis; Inflammatory; Systemic lupus erythematosus (SLE); Steroid-refractory chronic graft-versus-host disease (GvHD); Single-dose study; Efavaleukin alfa; Regulatory T Cells (Tregs)
• Other Study ID Numbers: 20200102

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
• product manufactured in and exported from the U.S.: Yes