A First in Human Study of the Safety, Tolerability, and the Physiologically Based Pharmacokinetics of XFB19 in Healthy Adult Volunteers.

NCT05361733 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: XFB19-101HT94252510985 (Log # PR241349)
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Xfibra, Inc. is conducting a Phase 1, randomized, double-blind, placebo-controlled, first-in-human study of the safety, tolerability, and physiologically-based pharmacokinetics (PK) of single and multiple ascending doses of XFB19 in healthy adult volunteers.

Conditions

Focus of the Study: Safety of XFB19

Keywords

human C/EBPβ-Thr266; XFB19

Outcome Measures

Primary Outcomes (11)

• Number of participants with adverse events

  Number of participants with adverse events (using the CTCAE v5.0 grading scale), with abnormal laboratory tests results (hematology, serum chemistry, coagulation, and urinalysis), abnormal vital signs, abnormal ECG parameters, and abnormal physical examination findings.

  During admission to the clinical unit (up to 10 days)

• Heart Rate (assessed by ECG)

  ECG parameters include the following: Heart Rate

  During admission to the clinical unit (up to 10 days)

• Rhythm (assessed by ECG)

  ECG parameters include the following: Rhythm

  During admission to the clinical unit (up to 10 days)

• P wave (assessed by ECG)

  ECG parameters include the following: P wave

  During admission to the clinical unit (up to 10 days)

• PR interval (assessed by ECG)

  ECG parameters include the following: PR interval

  During admission to the clinical unit (up to 10 days)

• QRS complex (assessed by ECG)

  ECG parameters include the following: QRS complex

  During admission to the clinical unit (up to 10 days)

• ST segment (assessed by ECG)

  ECG parameters include the following: ST segment

  During admission to the clinical unit (up to 10 days)

• T wave (assessed by ECG)

  ECG parameters include the following: T wave

  During admission to the clinical unit (up to 10 days)

• QT interval (assessed by ECG)

  ECG parameters include the following: QT interval

  During admission to the clinical unit (up to 10 days)

• Cardiac axis (assessed by ECG)

  ECG parameters include the following: Cardiac axis

  During admission to the clinical unit (up to 10 days)

• J-point (assessed by ECG)

  ECG parameters include the following: J-point

  During admission to the clinical unit (up to 10 days)

Secondary Outcomes (10)

• Maximum observed concentration (Cmax)

  During admission to the clinical unit (up to 10 days)

• Time to Cmax (Tmax)

  During admission to the clinical unit (up to 10 days)

• Trough concentration (Ctrough)

  During admission to the clinical unit (up to 10 days)

• Area under the plasma drug concentration-time curve (AUC0-tlast).

  During admission to the clinical unit (up to 10 days)

• Apparent terminal elimination half-life (t1/2)

  During admission to the clinical unit (up to 10 days)

Other Outcomes (2)

• Transcriptome in blood cells.

  During admission to the clinical unit (up to 10 days)

• Inflammatory proteins in blood.

  During admission to the clinical unit (up to 10 days)

Study Arms (2)

XFB19 administered SC.

EXPERIMENTAL

Part A: XFB19 SC injection at the following dose levels: * Cohort A1: 5 mg (or placebo vehicle , same volume) * Cohort A2: 10 mg (or placebo vehicle , same volume) * Cohort A3: 20 mg (or placebo vehicle , same volume) Part B: XFB19 SC injection at the 2 highest acceptable dose levels from Part A: * Cohort B1: second highest acceptable dose level from Part A (or placebo vehicle , same volume) * Cohort B2: highest acceptable dose level from Part A (or placebo vehicle , same volume)

Drug: XFB19

Placebo

PLACEBO COMPARATOR

10 healthy volunteers will be randomized and assigned to the Placebo arm in Part A (Cohorts A1, A2 and A3) and Part B (Cohorts B1 and B2).

Drug: Placebo

Interventions

XFB19 DRUG

The site-specific phosphorylation of the CCAAT/enhancer binding protein β (C/EBPβ) on Threonine266 (phospho-C/EBPβThr266) is critical for the priming and activation pathways, signals 1 and 2 of the NLRP3 inflammasome, that result in its full induction, causal to systemic inflammation critical to the morbidity and mortality of inflammatory/fibrotic diseases. Phospho-C/EBPβThr266 is also essential for the mesenchymal myofibroblastic cell cycle checkpoint failure and transition that results in the inappropriate tissue repair and pathological tissue fibrosis. XFB19 is a first-in-class, rationally-designed drug. It is homeostatic, and in preclinical studies, effectively, safely, and selectively inhibits phospho-C/EBPβThr266, the pathological inflammatory-fibrotic complications of NLRP3 inflammasome activation and synergistic myofibroblastic transition, reversing the pathology towards homeostasis, and fulfilling the precision medicine objectives.

XFB19 administered SC.

Placebo DRUG

No active ingredient drug use to blind participants and investigators

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects.
• Adult males and females, 18 to 55 years of age (inclusive) at screening.
• Body mass index ≥ 18.0 and ≤ 35.0 kg/m2 with a body weight ≥ 45 kg at screening.
• Be non-smokers (including tobacco, e-cigarettes, and marijuana) for at least 1 month prior to first investigational drug administration.
• Medically healthy without clinically significant abnormalities (in the opinion of the Investigator) at the Screening Visit and prior to dosing including:
• Physical examination without any clinically significant findings
• Systolic blood pressure in the range of 90 to 160 mmHg (inclusive) and diastolic blood pressure in the range of 50 to 95 mmHg (inclusive) after 5 minutes rest in supine position
• Heart rate (HR) in the range of 40 to 100 bpm (inclusive) after 5 minutes rest in supine position
• Body temperature (tympanic or oral) in the range of 35.5°C to 37.7°C (inclusive)
• No clinically significant findings in serum chemistry, hematology, coagulation, and urinalysis tests
• Triplicate 12-lead ECGs (taken after the volunteer has been supine for at least 5 minutes) with QT intervals corrected using Fridericia's method (QTcF) ≤ 450 msec for males and ≤ 470 msec for females and no clinically significant abnormalities
• Female volunteers must:
• Be of nonchildbearing potential, i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral tubal ligation, bilateral oophorectomy at least 6 weeks before screening) or postmenopausal (defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone \[FSH\] level \> 40 IU/L at the Screening Visit) OR
• If of childbearing potential, must agree not to donate ova, not to attempt to become pregnant, and, if engaging in sexual intercourse with a male partner, must agree to use an acceptable method of contraception from the time of signing the participant informed consent form (PICF) until at least 30 days after the last dose of the study drug
• Male volunteers must agree not to donate sperm, and, if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use an acceptable method of contraception from the time of signing the consent form until at least 30 days after the last dose of study drug.

You may not qualify if:

• History or presence of any clinically significant (as determined by the PI) cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, or neurological disease, including any acute illness or major surgery, within the past 3 months.
• Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic, or antiviral medications.
• Any history of malignant disease in the last 5 years (excluding surgically resected skin squamous cell or basal cell carcinoma).
• Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
• Use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 3 months prior to the first study drug administration.
• History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrythmia.
• Liver function test (LFT) results \> 1.5 times the upper limit of normal (ULN) for gamma glutamyl transferase (GGT), bilirubin (total, conjugated, and unconjugated), alkaline phosphatase (ALP), aspartate aminotransferase (AST), or alanine aminotransferase (ALT). Volunteers with bilirubin, ALP and/or ALT/AST above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs.
• Positive test results for human immunodeficiency virus (HIV-1 or HIV-2) antibodies, hepatitis C virus (HCV) antibodies, or hepatitis B surface antigen (HBsAg) at the Screening Visit. Patients with HCV antibodies, or HBsAg could be included if the viral load for HCV or hepatitis B are negative.
• Positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via polymerase chain reaction or commercially validated antigen test, per site's standard clinical procedure.
• Presence of sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
• Estimated creatinine clearance (CrCl) \< 60 mL/min using the Cockcroft-Gault formula or serum creatinine more than 1.5 x ULN.
• History of substance abuse or alcohol abuse (defined as more than 10 standard drinks per week or regularly consuming more than 4 standard drinks per day where 1 standard drink is 10 g of pure alcohol and equivalent to 285 mL beer \[4.9% Alc./Vol\], 100 mL wine \[12% Alc./Vol\], or 30 mL spirit \[40% Alc./Vol\]) within 12 months prior to the Screening Visit.
• Positive drugs of abuse or alcohol breath test results at the Screening Visit or at CRU check in (Day -1) (repeat tests allowed if false positive suspected). Non-habitual use and agreement to refrain from using any THC/CBD products during the study is allowed.
• Use of any prescription or over the counter (OTC) medication (including herbal products, diet aids, and hormone supplements) within 10 days or 5 half-lives of the medication (whichever is longer) prior to the first study drug administration, excepting use of contraceptives and occasional use of acetaminophen (up to 1 g every 8 hours or 3 g per day maximum).
• Demonstrated clinically significant (required intervention, e.g., emergency room visit, epinephrine administration) allergic reactions (e.g., food, drug, or atopic reactions, asthmatic episodes) which, in the opinion of the Investigator, would interfere with the volunteer's ability to participate in the study.

Sponsors & Collaborators

• Xfibra, Inc.: lead
• PharPoint Research, Inc.: collaborator
• Safe Harbor Pharmacovigilance: collaborator

Study Sites (1)

AMR Clinical

Knoxville, Tennessee, 37920, United States

RECRUITING

Related Publications (5)

• Buck M, Chojkier M. A ribosomal S-6 kinase-mediated signal to C/EBP-beta is critical for the development of liver fibrosis. PLoS One. 2007 Dec 26;2(12):e1372. doi: 10.1371/journal.pone.0001372.

  PMID: 18159255 BACKGROUND

• Buck M, Chojkier M. C/EBPbeta associates with caspase 8 complex proteins and modulates apoptosis in hepatic stellate cells. J Clin Gastroenterol. 2007 Nov-Dec;41 Suppl 3:S295-9. doi: 10.1097/MCG.0b013e31814927d5.

  PMID: 17975479 BACKGROUND

• Buck M, Chojkier M. C/EBPbeta-Thr217 phosphorylation signaling contributes to the development of lung injury and fibrosis in mice. PLoS One. 2011;6(10):e25497. doi: 10.1371/journal.pone.0025497. Epub 2011 Oct 5.

  PMID: 21998664 BACKGROUND

• Buck M, Poli V, Hunter T, Chojkier M. C/EBPbeta phosphorylation by RSK creates a functional XEXD caspase inhibitory box critical for cell survival. Mol Cell. 2001 Oct;8(4):807-16. doi: 10.1016/s1097-2765(01)00374-4.

  PMID: 11684016 BACKGROUND

• Buck M, Solis-Herruzo J, Chojkier M. C/EBPbeta-Thr217 Phosphorylation Stimulates Macrophage Inflammasome Activation and Liver Injury. Sci Rep. 2016 Apr 12;6:24268. doi: 10.1038/srep24268.

  PMID: 27067260 BACKGROUND

Study Officials

• Martina M Buck, Ph.D.

  Xfibra, Inc.

  STUDY CHAIR

Central Study Contacts

Mario Chojkier, M.D.

CONTACT

858-864-3588; mchojkier@gmail.com

Ed Parsley, D.O

CONTACT

713-899-2450; eparsley@att.net

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sponsor
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In Part A, 24 healthy volunteers will be enrolled in a total of 3 cohorts (Cohorts A1 to A3) with ascending doses of XFB19: 5mg (Cohort A1), 10mg (Cohort A2), and 20mg (Cohort A3). Each cohort will enroll 8 participants with 6 participants randomized to receive XFB19 and 2 participants randomized to receive placebo. In Part B, 16 healthy volunteers will be enrolled in a total of 2 cohorts (Cohorts B1 and B2). Each cohort will enroll 8 participants with 6 participants randomized to receive XFB19 and 2 participants randomized to receive placebo. Cohorts B1 and B2 will accept the second highest and highest XFB19 doses for evaluation from Part A.

Study Record Dates

• First Submitted: April 8, 2022
• First Posted: May 5, 2022
• Study Start: February 17, 2026
• Primary Completion (Estimated): September 15, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)