Natrunix Safety PK Study in Healthy Volunteers

A Phase I Open Label, Placebo-controlled Dose Escalation Study to Evaluate Safety and Pharmacokinetics of NatrunixTM 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: Recruiting
• Conditions: Pharmacokinetics
• Intervention / Treatment: Biological: NatrunixTM; 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 (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Haritha Pallapotu, MS; Phone Number: 512-386-2992; Email: hpallapotu@xbiotech.com
• Study Contact Backup: Name: Norma Gonzalez; Phone Number: 512-386-2903; Email: ngonzalez@xbiotech.com

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78759
      • Recruiting
      • BioBehavioral Research of Austin, A Telemed2U Company
      • Contact: Alexsandria DeLeon; Phone Number: 512-382-6661; Email: Alexsandria@bbraustin.com
      • Principal Investigator: Neha Reshamwala, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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: NatrunixTM; Each participant will receive one single subcutaneous injection of 200 mg (Cohort 1), 400 mg (Cohort 2), or 800 mg (Cohort 3) of NatrunixTM.	Biological: NatrunixTM; The active ingredient in the drug product NatrunixTM is XB2001, a recombinant human IgG4 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 human IgG4-kappa, 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 will receive one single subcutaneous injection of placebo.	Biological: Placebo; Placebo control for NatrunixTM subcutaneous injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with treatment related adverse events assessed according to CTCAE v5.0	Participants will be monitored for acute reactions, blood chemistry and hematology immediately after dosing and at multiple time points up to 28 days. All adverse events will be documented at multiple time points and assessed in terms those possibly, probably and definitely related to test article according to CTCAE v4.0 criteria. Anti-drug antibodies (ADA) will also be evaluated.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration of test article 2) Terminal plasma concentration 3) Plasma half-life 4) Total exposure	The maximum plasma concentration will be assessed using a proprietary immunoassay to detect circulating NatrunixTM	28 days
Terminal plasma concentration	Terminal plasma concentration will be assessed at 28 days.	28 days
Half-life	Peak and terminal plasma levels will be used in a two compartmental model to assess plasma half-life.	28 days
Total exposure	Area under the curve will be determined based on measured plasma levels over 28 days.	28 days

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 (Anticipated): May 1, 2022
• Study Completion (Anticipated): June 15, 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): February 24, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this 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