Safety and Pharmacokinetics (PK) Study of Natrunix in Healthy Volunteers

A Phase I Open-label, Placebo-controlled Dose Escalation Study to Evaluate Safety and Pharmacokinetics of Natrunix Via Subcutaneous Injection in Healthy Subjects

This trial will be a Phase I open-label, placebo-controlled dose escalation study to evaluate safety and pharmacokinetics of Natrunix via subcutaneous injection in healthy subjects. The target enrollment is 8 healthy subjects per cohort (including six for Natrunix and two for placebo). Three cohorts for a total of 24 healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: Biological: Natrunix; Biological: Placebo

Detailed Description

Study Title: A Phase I open-label, placebo-controlled dose escalation study to evaluate safety and pharmacokinetics of Natrunix via subcutaneous injection in healthy subjects.

Sponsor: XBiotech USA, Inc.

Study Chair: Neha Reshamwala, MD

Number of Planned Subjects: Eight healthy subjects per cohort (including six for Natrunix and two for placebo). Three cohorts for a total of 24 healthy volunteers.

Approximate Duration: Approximately 38 days for each subject which includes a screening period of up to 10 days followed by one subcutaneous dose of Natrunix, and then evaluation over 28 days. Blood will be sampled at various time points for blood chemistry, hematological analysis, and Natrunix serum/plasma concentrations.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78759
      • BioBehavioral Research of Austin, A Telemed2U Company

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age: ≥ 18

2. Adequate bone marrow function defined as:

   • absolute neutrophil count (neutrophil and bands) of ≥ 1,500/mm3 (≥ 1.5 x 109/L)
   • platelet count > 150,000/mm3
   • hemoglobin of ≥ 10 g/dL
3. Adequate renal function, defined by serum creatinine ≤ 1.5 x lab ULN.
4. Adequate hepatic function defined as:
5. serum albumin ≥ 3.0 g/dL
6. total bilirubin ≤ 1.5 times lab ULN.
7. alanine aminotransferase (ALT) ≤ 2.0 times lab ULN.
8. aspartate aminotransferase (AST) ≤ 2.0 times lab ULN
9. For WOCBP, a negative pregnancy test at screening. For subjects with reproductive potential, willingness to use one method of contraception of high efficacy during the entire study period. These methods can include but not limited to hormonal contraceptives, intrauterine devices, condoms, diaphragms etc. Women of non-childbearing potential include those considered to have a medical history that indicates that pregnancy is not a reasonable risk, including post-menopausal women and those with a history of hysterectomy or surgically sterilized.
10. If the participant is a male participating in this clinical research study, the subject should not get a sexual partner pregnant during participation in this research study as the effect of the study drug on sperm is not known. The male contraception methods can include but not limited to mechanical methods (abstinence, withdrawal, non-vaginal intercourse) or contemporary methods comprising condoms and vasectomy.
11. Signed and dated Institutional Review Board (IRB) approved informed consent before any protocol-specific screening procedures are performed.

Exclusion Criteria:

1. Treatment with any biologicals (including intravenous immunoglobulin) or investigational agents within the last 4 weeks (or 5 half-lives, whichever is longer).

2. Uncontrolled or significant cardiovascular disease, including:

   • A myocardial infarction within the past 6 months.
   • Uncontrolled angina within the past 3 months.
   • Congestive heart failure within the past 3 months, defined as New York Heart Association (NYHA) Class II or higher.
   • Uncontrolled hypertension (blood pressure >160 mm Hg systolic or >100 mm Hg diastolic).
3. Dementia or altered mental status that would prohibit the understanding or rendering of informed consent.
4. Treatment with immunosuppressant agents, including corticosteroids or cyclosporine within the last 4 weeks.
5. Serious uncontrolled medical disorders, such as uncontrolled diabetes, active peptic ulcer disease, cerebrovascular accident within three months, ongoing congestive heart failure, and any other condition, which in the opinion of the investigator, would put the subject at risk by participating in the trial.
6. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
7. Abnormal ECG with any clinically significant findings or with QTc > 470 ms.
8. Infection requiring treatment with antibiotics within 3 weeks prior to screening.

9. Infectious disease:

   • Positive HIV, RPR, Hepatitis B or C, TB (QuantiFERON-TB Gold (QFT)/ IGRA)

10. History of immunodeficiency.
11. Female subjects who are pregnant, planning to become pregnant during the course of the study, or breast-feeding.
12. Major surgery within 28 days prior to Day 0.
13. History of progressive multifocal leukoencephalopathy (PML) or other demyelinating disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Natrunix; Each participant receives one single subcutaneous injection of 100 mg (Cohort 1), 200 mg (Cohort 2), or 400 mg (Cohort 3) of Natrunix.	Biological: Natrunix; The active ingredient in the drug product Natrunix is XB2001, a recombinant human Immunoglobulin G4 monoclonal antibody specific for human interleukin-1-alpha (IL-1-alpha). The entire XB2001 heavy and light chain sequences are identical to those found in naturally-occurring humans, with the light and heavy chain variable regions being identical to those originally expressed by a peripheral blood B lymphocyte that was obtained from a healthy individual.
Placebo Comparator: Placebo; Each participant receives one single subcutaneous injection of 0.5 ml (Cohort 1), 1 ml (Cohort 2), or 2 ml (Cohort 3) of Placebo.	Biological: Placebo; Placebo control for Natrunix subcutaneous injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events	Participants were monitored for treatment-emergent adverse events (TEAEs) immediately after the initial subcutaneous administration on Day 0 (Visit 1) through the final follow-up on Day 28 (Visit 7). All identified adverse events were documented and graded for severity according to the "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."	From Day 0 up to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax)	This outcome measure represents the peak exposure following a single subcutaneous administration of Natrunix. Cmax is assessed using a proprietary immunoassay. Placebo participants were not assessed for PK Outcome Measures	Plasma samples were collected at the following intervals: Day 0: Pre-injection and at 3, 6, and 10 hours post-injection. Post-Injection Follow-up: Days 2, 3, 4, 14, and 28.
Terminal Plasma Concentration	This outcome measure evaluates the circulating drug levels at the end of the study observation period. Plasma samples were analyzed using a validated proprietary immunoassay to detect and quantify concentration levels of Natrunix. Placebo participants were not assessed for PK Outcome Measures	Day 28
Half-life	Half-life is calculated by Thermo-Scientific Kinetica Version 5.1 SP1, using average observed Natrunix plasma concentration of all time points of all patients for each treatment cohort. Placebo participants were not assessed for PK Outcome Measures	Plasma samples were collected at the following intervals: Day 0: Pre-injection and at 3, 6, and 10 hours post-injection. Post-Injection Follow-up: Days 2, 3, 4, 14, and 28.
Area Under the Curve	This outcome measure calculates the area Under the Concentration-Time Curve (AUC) from the time of administration (Day 0) through the final observation point at Day 28. Placebo participants were not assessed for PK Outcome Measures	Plasma samples were collected at the following intervals: Day 0: Pre-injection and at 3, 6, and 10 hours post-injection. Post-Injection Follow-up: Days 2, 3, 4, 14, and 28.

Collaborators and Investigators

• Sponsor: XBiotech, Inc.
• Investigators: Principal Investigator: Neha Reshamwala, MD, BioBehavioral Research of Austin

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2022
• Primary Completion (Actual): August 8, 2022
• Study Completion (Actual): August 8, 2022

Study Registration Dates

• First Submitted: September 16, 2021
• First Submitted That Met QC Criteria: October 18, 2021
• First Posted (Actual): October 29, 2021

Study Record Updates

• Last Update Posted (Actual): August 14, 2026
• Last Update Submitted That Met QC Criteria: June 25, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Dose escalation study
• Other Study ID Numbers: 2021-PT053

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No It is not yet known if there will be a plan to make IPD available

Drug and device information, study documents

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