Pharmacokinetics of IFX and TNF Concentrations in Serum, Stool, and Colonic Mucosa in Acute Severe Ulcerative Colitis

N/AActive Not RecruitingNCT03765450

Alimentiv Inc.18 enrolled

Overview

This is an open-label, prospective, observational study with the primary objective to characterize the pharmacokinetics of infliximab in patients with Acute Severe Ulcerative Colitis.

In Acute Severe Ulcerative Colitis (ASUC), drug exposure may be affected by intestinal protein loss leading to hypoalbuminemia and rapid clearance of infliximab (IFX). Importantly, 2 studies have associated the loss of IFX in stool with poor outcomes. Multiple observational studies have identified that patients with faster IFX clearance have worse clinical outcomes and higher rates of antidrug antibody formation. To better understand optimal dosing of IFX in ASUC, the pharmacokinetics of IFX in association with outcomes must be better defined in this setting.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Ulcerative Colitis

Interventions

InfliximabDRUG

Patients will receive infliximab at the discretion of their physician as part of standard of care.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Present to hospital with ASUC based on Truelove and Witts criteria,33 defined as the presence of more than 6 bloody stools per day along with any 1 of the following: tachycardia \> 90 beats per minute, fever \> 37.8 °C, hemoglobin \< 10.5 g/dL, and erythrocyte sedimentation rate (ESR) \> 30 mm/h (or CRP \> 30 mg/L \[high-sensitivity CRP \> 300 mg/L\]) is a suitable surrogate if ESR is not available1). * Have a partial MCS \> 7. * Have a Mayo Clinic ES ≥ 2 with disease extending 15 cm or more beyond the anal verge. * Require rescue inpatient IFX infusion as part of routine care. Note, the IFX treatment regimen is not defined by this protocol and any dosage regimen is acceptable for the purposes of this study, such as standard or accelerated induction regimens. * Be able to speak English and participate fully in all aspects of this clinical trial. * Provide written informed consent. Exclusion Criteria: * A known history of being positive for anti-IFX antibodies. * Have a serious active infection, active malignancy, or any other known condition contraindicated with infliximab therapy, according to current prescribing information. * Serious underlying disease other than ASUC, or other physical or psychosocial condition that, in the opinion of the investigator, may interfere with the subject's ability to participate fully in the study. * Prior enrollment in the current study.

Locations (3)

UCSD

San Diego, California, United States

Cornell University

New York, New York, United States

Mount Sinai Hospital

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

Inter-compartmental Difference in Infliximab Concentration

Infliximab population pharmacokinetics

Time frame: 22 weeks

Secondary Outcomes

Change in Proteome

Change in Proteomics before and after therapy

Time frame: 22 weeks

Change in Transcriptome

Change in Transcriptomics before and after therapy

Time frame: 22 weeks

Change in Robarts Histopathologic Index

Change in Robarts Histopathologic Index before and after therapy The RHI consists of 4 histological items (extent of chronic inflammatory cell infiltration, neutrophils in the lamina propria, neutrophils in the epithelium, and erosions and ulceration) scored from 0 to 3 and multiplied by a weighting factor. The total RHI score is calculated by summing the weighted scores of the histological items, with total scores ranging from 0 (no disease activity) to 33 (severe disease activity).

Time frame: 22 weeks

Change in Mayo Clinic Endoscopic Score

Change in Mayo Clinic Endoscopic Score before and after therapy The Mayo Clinic score (MCS) scores 4 variables (stool frequency, rectal bleeding, a physician's global assessment and endoscopic findings with flexible sigmoidoscopy). The endoscopic component of the MCS assesses disease activity on a 4-point scale (0-3 points), with higher scores representing more severe disease activity. Mucosal healing is often defined as an endoscopy score of 0 or 1. Normal or inactive disease = 0 Mild disease (erythema, decreased vascular pattern, mild friability) = 1 Moderate disease (marked erythema, absent vascular pattern, friability, erosions) = 2 Severe (spontaneous bleeding, ulceration) = 3

Time frame: 22 weeks

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.