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

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

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.

Study Overview

• Status: Completed
• Conditions: Safety in Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: XmAb27564

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ralph Zitnik, MD; Phone Number: 650-996-5321; Email: rzitnik@xencor.com
• Study Contact Backup: Name: Seven Lueder-Powers; Phone Number: 858-769-6357; Email: slueder-powers@xencor.com

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78209
      • ICON Early Phase Services, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Xencor, Inc.
• Collaborators: ICON Clinical Research
• Investigators: Study Director: Ralph Zitnik, MD, Executive Medical Director, Clinical Development, Xencor

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2021
• Primary Completion (Actual): November 10, 2022
• Study Completion (Actual): November 10, 2022

Study Registration Dates

• First Submitted: April 14, 2021
• First Submitted That Met QC Criteria: April 20, 2021
• First Posted (Actual): April 23, 2021

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Healthy Volunteers
• Other Study ID Numbers: XmAb27564-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No