A Study to Evaluate the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AMG 592 in Healthy Participants

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the safety, tolerability and immunogenicity profile of single and multiple dose administrations of AMG 592 in healthy participants.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Single-ascending Dose Study to Evaluate the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AMG 592 in Healthy Subjects

Conditions
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Chronic Graft-versus-host Disease (cGVHD)

Intervention / Treatment
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* Drug: AMG 592
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males must agree to practice an acceptable method of effective birth control while on study through 2 weeks after receiving the dose of study drug. Males must be willing to abstain from sperm donation while on study through 2 weeks after receiving the (last [multiple dose studies]) dose of study drug. Male and female subjects ≥ 18 and ≤ 55 years of age with a body mass index (BMI) of ≥ 18.0 and ≤ 32.0 kg/m^2 at the time of screening. Females must be of non-reproductive potential (ie, postmenopausal - age ≥ 55 years with cessation of menses for 12 months or more, or according to the definition of postmenopausal range for the laboratory involved OR history of hysterectomy; OR history of bilateral oophorectomy). Exclusion Criteria: Positive Hepatitis B Surface Antigen (HepBsAg) (indicative of chronic Hepatitis B) or detectable Hepatitis C virus Ribonucleic acid (RNA) by Polymerase Chain Reaction (PCR) (indicative of active Hepatitis C - screening is generally done by Hepatitis C Antibody (HepCAb), followed by Hepatitis C virus RNA by PCR if HepCAb is positive). Positive results for Human Immunodeficiency Virus (HIV). Participant has a history of residential exposure to tuberculosis without a documented history of prophylactic treatment of tuberculosis or participant has a positive purified protein derivative (PPD) or QuantiFERON or T-Spot test at Screening. Participants with a documented negative PPD or QuantiFERON or T-Spot test within 4 weeks prior to screening who have no known tuberculosis exposure and have not traveled to an area with tuberculosis do not need to have a test performed at screening. Currently receiving treatment in another investigational device or drug study, or less than 30 days or less than 5 half-lives, whichever is longer, since ending treatment on another investigational device or drug study. Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years. Any active infection for which systemic anti-infectives were used within 4 weeks prior to Day 1. Females who are lactating/breastfeeding or who plan to breastfeed while on study through 2 weeks after receiving the dose of study drug. Female participants with a positive pregnancy test. Males with partners who are pregnant or planning to become pregnant while the participant is on study through 2 weeks after receiving the dose of study drug. Has any significant abnormality during the screening physical examination, electrocardiogram (ECG), or laboratory evaluation that in the opinion of the Investigator, in consultation with the Amgen Medical Monitor, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion. Unwilling or unable to abstain from alcohol consumption within 48 hours prior to each visit (including Screening). Is a current smoker, has used any nicotine or tobacco containing products (including but not limited to: snuff, chewing tobacco, cigars, cigarettes, pipes, or nicotine patches) within the last 6 months from Screening, and cumulative smoking history is ≥ 10 pack years. Unwilling or unable to refrain from strenuous exercise (eg, heavy lifting, weight training, and aerobics) for 72 hours prior to each visit that includes blood collection. Has donated or lost ≥ 500 mL of blood or plasma within 8 weeks of administration of the first dose of IP. Participants with a known history of autoimmune disease.

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG 592: Dose 1<br>Administered as a single dose subcutaneous (SC) injection. | Drug: AMG 592<br>* Administered as SC injection<br>|
| Experimental: AMG 592: Dose 2<br>Administered as a single dose SC injection. | Drug: AMG 592<br>* Administered as SC injection<br>|
| Experimental: AMG 592: Dose 3<br>Administered as a single dose SC injection. | Drug: AMG 592<br>* Administered as SC injection<br>|
| Experimental: AMG 592: Dose 4<br>Administered as a single dose SC injection. | Drug: AMG 592<br>* Administered as SC injection<br>|
| Experimental: AMG 592: Dose 5<br>Administered as a single dose SC injection. | Drug: AMG 592<br>* Administered as SC injection<br>|
| Experimental: AMG 592: Dose 6<br>Administered as a single dose SC injection. | Drug: AMG 592<br>* Administered as SC injection<br>|
| Experimental: AMG 592: Dose 7<br>Administered as a single dose SC injection. | Drug: AMG 592<br>* Administered as SC injection<br>|
| Experimental: AMG 592: Dose 8<br>Administered as a single dose SC injection. | Drug: AMG 592<br>* Administered as SC injection<br>|
| Placebo Comparator: Placebo<br>Administered as SC injection. | Other: Placebo<br>* Administered as SC injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) | Any clinically significant changes in physical examinations, clinical laboratory tests and vital signs will be recorded as TEAEs. | Day 1 up to Day 57 | 
| Number of Participants with Anti-AMG 592 Antibodies |  | Day 1 up to Day 57 | 
| Fold Change from Baseline in Absolute Cell Counts of Regulatory T Cells (Tregs) |  | One week after AMG 592 administration (up to 7 days) | 
| Fold Change from Baseline in Absolute Cell Counts of Conventional T Cells (Tcons) |  | One week after AMG 592 administration (up to 7 days) | 
| Fold Change from Baseline in Absolute Cell Counts of Natural Killer Cells (NKs) |  | One week after AMG 592 administration (up to 7 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Serum Concentration (Cmax) of AMG 592 |  | Day 1 up to Day 57 | 
| Time of Maximum Observed Concentration (tmax) of AMG 592 |  | Day 1 up to Day 57 | 
| Area Under the Concentration-time Curve (AUC) of AMG 592 |  | Day 1 up to Day 57 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Graft-versus-Host Disease, AMG 592, Inflammatory Conditions