Safety, Tolerability and PK of a Single Subcutaneous Injection of XmAb27564 in Healthy Volunteers

Study Overview
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Brief Summary
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This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending-dose study of subcutaneously administered XmAb27564 or placebo in healthy male and female subjects.

Detailed Description
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This study will determine the safety and tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of XmAb27564 in normal healthy volunteers. XmAb27564 is an engineered IL-2 mutein being developed for autoimmune diseases.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Ascending-Dose Study of the Safety, Tolerability, and Pharmacokinetics of XmAb®27564 in Healthy Volunteers

Conditions
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Safety in Healthy Volunteers

Intervention / Treatment
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* Drug: XmAb27564
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Total body weight 50.0 to 100.0 kg and body mass index (BMI) 19.0 to 35.0 kg/m2 In good general health with no clinically significant abnormality identified on medical or laboratory evaluation and no history of any clinically significant disorder, condition, or disease. A nonsmoker for at least 12 weeks preceding screening Female subjects of childbearing potential must agree to use a highly effective method of birth control during and for 45 days after administration of investigational product (IP). Fertile male and female subjects must be willing to practice a highly effective method of birth control during and for 45 days after administration of IP and agree not to donate sperm from screening through 45 days after administration of IP. Exclusion Criteria: Subjects who have a clinically relevant history or presence of diseases or disorders that would pose a significant risk to subject's safety or significantly interfere with the study evaluation, procedures, or completion Subjects with history of any cardiovascular event Subjects with vital sign values outside the normal ranges Subjects who are positive for MTB QuantiFERON, hepatitis B surface antigen, hepatitis C virus antibody, severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) by polymerase chain reaction (PCR)/antigen, or human immunodeficiency virus Type I or Type II tests at screening Subjects with signs or symptoms consistent with active viral infection Subjects with baseline eosinophil elevation or a history of urticaria, asthma, allergic dermatitis, food allergy or eosinophilic esophagitis Subjects who have evidence of any bacterial, viral, parasitic, or systemic fungal infections requiring treatment within the 21 days prior to randomization; or hospitalization due to infection within 3 months prior to randomization Subjects who have had any prior investigational treatment with interleukin 2 (IL-2) therapies or have received any investigational agent within five half-lives of the study drug Subjects with a known or suspected sensitivity to products from mammalian cell lines Subjects who have received live vaccines ≤ 2 months prior to screening or any vaccine within the past 14 days

Ages Eligible for Study
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Minimum Age: 21 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose - XmAb27564 Subcutaneous injection of Dose A, B, C, D, E or F<br> | Drug: XmAb27564<br>* Single ascending dose of XmAb27564<br>|
| Placebo Comparator: Single Ascending Dose - Placebo Subcutaneous injection of placebo<br> | Drug: Placebo<br>* Single dose of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events, graded by CTCAE Version 5.0 |  | Up to Day 45 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK: Area Under the Drug Concentration - Time Curve from Zero to the End of Observation |  | 45 Days | 
| PK: Maximum Observed Drug Concentration (Cmax) of XmAb27564 after a single dose |  | 45 Days | 
| PK: Measurement of Cmax |  | 45 Days | 
| PK: Time to Maximum Plasma Concentration (Tmax) of XmAb27564 after a single dose |  | 45 Days | 
| PK: Measurement of Tmax |  | 45 Days | 
| PK: Time to Decrease in Concentration by Half (T1/2) of XmAb27564 after a single dose, due to elimination |  | 45 Days | 
| PK: Measurement of T1/2 |  | 45 Days | 
| PD: Measurement of Change in Number of Regulatory T Cells |  | 45 Days | 
| PD: Measurement of Change in Number of Subsets of Conventional T Cells in Blood |  | 45 Days | 
| PD: Measurement of Change in Number of Natural Killer Cells (NK Cells) in Blood |  | 45 Days | 
| PD: Measurement of Cytokines in Blood |  | 45 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteers