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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Inflammatory Diseases

Intervention / Treatment
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* Drug: Efavaleukin alfa


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Serum Concentration (Cmax) of Efavaleukin Alfa |  | Up to Day 43 | 
| Time of the Maximum Observed Serum Concentration (Tmax) of Efavaleukin Alfa |  | Up to Day 43 | 
| Area Under the Serum Concentration Time Curve from Time Zero to Time of Last Quantifiable Concentration (AUClast) of Efavaleukin Alfa |  | Up to Day 43 | 
| Area Under the Serum Concentration Time Curve from Time Zero to Infinity (AUCinf) of Efavaleukin Alfa |  | Up to Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants who Experience One or More Treatment-emergent Adverse Events (TEAEs) | Adverse events (AEs) are defined as any untoward medical occurrence in clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in physical examinations, clinical laboratory tests and vital signs will be recorded as TEAEs. Serious AEs (SAEs) are defined as any event that meets at least 1 of the following serious criteria: Results in death (fatal) Requires in-patient hospitalization or prolongation of existing hospitalization Results in persistent or significant disability/incapacity Is a congenital anomaly/birth defect Other medically important serious event | Day 1 to Day 43 | 
| Incidences of Anti-Eflavaleukin Alfa and Anti-Interleukin 2 (IL-2) Antibody Formation |  | Up to Day 43 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic lupus erythematosus (SLE), Steroid-refractory chronic graft-versus-host disease (GvHD), Ulcerative colitis, Single-dose study, Efavaleukin alfa, Regulatory T Cells (Tregs), Inflammatory