Inflammatory Diseases
Conditions
Keywords
Systemic lupus erythematosus (SLE), Steroid-refractory chronic graft-versus-host disease (GvHD), Ulcerative colitis, Single-dose study, Efavaleukin alfa, Regulatory T Cells (Tregs), Inflammatory
Brief summary
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.
Interventions
DRUGEfavaleukin alfa
Administered as a single dose SC injection.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Serum Concentration (Cmax) of Efavaleukin Alfa | 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 | Blood samples were collected to determine PK parameters. |
| Time of the Maximum Observed Serum Concentration (Tmax) of Efavaleukin Alfa | 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 | Blood samples were collected to determine PK parameters. |
| Area Under the Serum Concentration Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Efavaleukin Alfa | 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 | Blood samples were collected to determine PK parameters. |
| Area Under the Serum Concentration Time Curve From Time Zero to Infinity (AUCinf) of Efavaleukin Alfa | 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 | Blood samples were collected to determine PK parameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Day 1 to Day 43 | 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 |
| Number of Participants With Anti-Efavaleukin Alfa Antibodies and Anti-Interleukin 2 (IL-2) Antibodies | Day 1 up to Day 43 | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
Participants were enrolled at 1 research center in the United Kingdom from August 2021 to October 2022.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Chinese Participants - Efavaleukin Alfa (Dose Level 1) Chinese participants who received efavaleukin alfa administered as one subcutaneous (SC) injection at dose level 1 (low). | 8 |
| Group 2: Chinese Participants - Efavaleukin Alfa (Dose Level 2) Chinese participants who received efavaleukin alfa administered as one SC injection at dose level 2 (high). | 8 |
| Group 3: Japanese Participants -Efavaleukin Alfa (Dose Level 2) Japanese participants who received efavaleukin alfa administered as one SC injection at dose level 2 (high). | 8 |
| Group 4: Caucasian Participants - Efavaleukin Alfa (Dose Level 2) Caucasian participants who received efavaleukin alfa administered as one SC injection at dose level 2 (high). | 8 |
| Total | 32 |
Baseline characteristics
| Characteristic | Group 1: Chinese Participants - Efavaleukin Alfa (Dose Level 1) | Group 2: Chinese Participants - Efavaleukin Alfa (Dose Level 2) | Group 3: Japanese Participants -Efavaleukin Alfa (Dose Level 2) | Group 4: Caucasian Participants - Efavaleukin Alfa (Dose Level 2) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 27.9 Years STANDARD_DEVIATION 4.55 | 28.3 Years STANDARD_DEVIATION 4.86 | 29.5 Years STANDARD_DEVIATION 4.11 | 37.9 Years STANDARD_DEVIATION 12.01 | 30.9 Years STANDARD_DEVIATION 7.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants | 8 Participants | 8 Participants | 0 Participants | 24 Participants |
| Race/Ethnicity, Customized White | 0 Participants | 0 Participants | 0 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 2 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 6 Participants | 3 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 8 / 8 | 8 / 8 | 8 / 8 | 8 / 8 |
| serious Total, serious adverse events | 1 / 8 | 0 / 8 | 1 / 8 | 0 / 8 |
Outcome results
Primary
Area Under the Serum Concentration Time Curve From Time Zero to Infinity (AUCinf) of Efavaleukin Alfa
Blood samples were collected to determine PK parameters.
Time frame: 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
Population: PK population: all participants who received at least 1 dose of efavaleukin alfa and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Chinese Participants - Efavaleukin Alfa (Dose Level 1) | Area Under the Serum Concentration Time Curve From Time Zero to Infinity (AUCinf) of Efavaleukin Alfa | 1700 hr*ng/mL | Geometric Coefficient of Variation 66.7 |
| Group 2: Chinese Participants - Efavaleukin Alfa (Dose Level 2) | Area Under the Serum Concentration Time Curve From Time Zero to Infinity (AUCinf) of Efavaleukin Alfa | 2350 hr*ng/mL | Geometric Coefficient of Variation 38.1 |
| Group 3: Japanese Participants -Efavaleukin Alfa (Dose Level 2) | Area Under the Serum Concentration Time Curve From Time Zero to Infinity (AUCinf) of Efavaleukin Alfa | 2590 hr*ng/mL | Geometric Coefficient of Variation 29 |
| Group 4: Caucasian Participants - Efavaleukin Alfa (Dose Level 2) | Area Under the Serum Concentration Time Curve From Time Zero to Infinity (AUCinf) of Efavaleukin Alfa | 2500 hr*ng/mL | Geometric Coefficient of Variation 43 |
Primary
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.
Time frame: 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
Population: PK population: all participants who received at least 1 dose of efavaleukin alfa and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Chinese Participants - Efavaleukin Alfa (Dose Level 1) | Area Under the Serum Concentration Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Efavaleukin Alfa | 1530 hr*ng/mL | Geometric Coefficient of Variation 70 |
| Group 2: Chinese Participants - Efavaleukin Alfa (Dose Level 2) | Area Under the Serum Concentration Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Efavaleukin Alfa | 2330 hr*ng/mL | Geometric Coefficient of Variation 38.8 |
| Group 3: Japanese Participants -Efavaleukin Alfa (Dose Level 2) | Area Under the Serum Concentration Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Efavaleukin Alfa | 2590 hr*ng/mL | Geometric Coefficient of Variation 29 |
| Group 4: Caucasian Participants - Efavaleukin Alfa (Dose Level 2) | Area Under the Serum Concentration Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Efavaleukin Alfa | 2660 hr*ng/mL | Geometric Coefficient of Variation 44.2 |
Primary
Maximum Observed Serum Concentration (Cmax) of Efavaleukin Alfa
Blood samples were collected to determine PK parameters.
Time frame: 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
Population: Pharmacokinetic (PK) population: all participants who received at least 1 dose of efavaleukin alfa and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Chinese Participants - Efavaleukin Alfa (Dose Level 1) | Maximum Observed Serum Concentration (Cmax) of Efavaleukin Alfa | 26.9 ng/mL | Geometric Coefficient of Variation 52.1 |
| Group 2: Chinese Participants - Efavaleukin Alfa (Dose Level 2) | Maximum Observed Serum Concentration (Cmax) of Efavaleukin Alfa | 41.6 ng/mL | Geometric Coefficient of Variation 33.4 |
| Group 3: Japanese Participants -Efavaleukin Alfa (Dose Level 2) | Maximum Observed Serum Concentration (Cmax) of Efavaleukin Alfa | 48.1 ng/mL | Geometric Coefficient of Variation 33 |
| Group 4: Caucasian Participants - Efavaleukin Alfa (Dose Level 2) | Maximum Observed Serum Concentration (Cmax) of Efavaleukin Alfa | 56.1 ng/mL | Geometric Coefficient of Variation 47.7 |
Primary
Time of the Maximum Observed Serum Concentration (Tmax) of Efavaleukin Alfa
Blood samples were collected to determine PK parameters.
Time frame: 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
Population: PK population: all participants who received at least 1 dose of efavaleukin alfa and had evaluable PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: Chinese Participants - Efavaleukin Alfa (Dose Level 1) | Time of the Maximum Observed Serum Concentration (Tmax) of Efavaleukin Alfa | 24.0 hours |
| Group 2: Chinese Participants - Efavaleukin Alfa (Dose Level 2) | Time of the Maximum Observed Serum Concentration (Tmax) of Efavaleukin Alfa | 24.0 hours |
| Group 3: Japanese Participants -Efavaleukin Alfa (Dose Level 2) | Time of the Maximum Observed Serum Concentration (Tmax) of Efavaleukin Alfa | 24.0 hours |
| Group 4: Caucasian Participants - Efavaleukin Alfa (Dose Level 2) | Time of the Maximum Observed Serum Concentration (Tmax) of Efavaleukin Alfa | 20.0 hours |
Secondary
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
Time frame: Day 1 to Day 43
Population: Safety population: all participants who received at least 1 dose of efavaleukin alfa and had at least 1 post-dose safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Chinese Participants - Efavaleukin Alfa (Dose Level 1) | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | All TEAEs | 8 Participants |
| Group 1: Chinese Participants - Efavaleukin Alfa (Dose Level 1) | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Serious TEAEs | 1 Participants |
| Group 2: Chinese Participants - Efavaleukin Alfa (Dose Level 2) | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Serious TEAEs | 0 Participants |
| Group 2: Chinese Participants - Efavaleukin Alfa (Dose Level 2) | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | All TEAEs | 8 Participants |
| Group 3: Japanese Participants -Efavaleukin Alfa (Dose Level 2) | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | All TEAEs | 8 Participants |
| Group 3: Japanese Participants -Efavaleukin Alfa (Dose Level 2) | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Serious TEAEs | 1 Participants |
| Group 4: Caucasian Participants - Efavaleukin Alfa (Dose Level 2) | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | All TEAEs | 8 Participants |
| Group 4: Caucasian Participants - Efavaleukin Alfa (Dose Level 2) | Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) | Serious TEAEs | 0 Participants |
Secondary
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.
Time frame: Day 1 up to Day 43
Population: Safety population: all participants who received at least 1 dose of efavaleukin alfa and had at least 1 post-dose safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Chinese Participants - Efavaleukin Alfa (Dose Level 1) | Number of Participants With Anti-Efavaleukin Alfa Antibodies and Anti-Interleukin 2 (IL-2) Antibodies | Anti-Efavaleukin Alfa Antibodies | 6 Participants |
| Group 1: Chinese Participants - Efavaleukin Alfa (Dose Level 1) | Number of Participants With Anti-Efavaleukin Alfa Antibodies and Anti-Interleukin 2 (IL-2) Antibodies | Anti-IL-2 Antibodies | 0 Participants |
| Group 2: Chinese Participants - Efavaleukin Alfa (Dose Level 2) | Number of Participants With Anti-Efavaleukin Alfa Antibodies and Anti-Interleukin 2 (IL-2) Antibodies | Anti-IL-2 Antibodies | 0 Participants |
| Group 2: Chinese Participants - Efavaleukin Alfa (Dose Level 2) | Number of Participants With Anti-Efavaleukin Alfa Antibodies and Anti-Interleukin 2 (IL-2) Antibodies | Anti-Efavaleukin Alfa Antibodies | 7 Participants |
| Group 3: Japanese Participants -Efavaleukin Alfa (Dose Level 2) | Number of Participants With Anti-Efavaleukin Alfa Antibodies and Anti-Interleukin 2 (IL-2) Antibodies | Anti-Efavaleukin Alfa Antibodies | 7 Participants |
| Group 3: Japanese Participants -Efavaleukin Alfa (Dose Level 2) | Number of Participants With Anti-Efavaleukin Alfa Antibodies and Anti-Interleukin 2 (IL-2) Antibodies | Anti-IL-2 Antibodies | 0 Participants |
| Group 4: Caucasian Participants - Efavaleukin Alfa (Dose Level 2) | Number of Participants With Anti-Efavaleukin Alfa Antibodies and Anti-Interleukin 2 (IL-2) Antibodies | Anti-Efavaleukin Alfa Antibodies | 7 Participants |
| Group 4: Caucasian Participants - Efavaleukin Alfa (Dose Level 2) | Number of Participants With Anti-Efavaleukin Alfa Antibodies and Anti-Interleukin 2 (IL-2) Antibodies | Anti-IL-2 Antibodies | 2 Participants |