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

Alimentiv

Status: Active, not recruiting

Conditions: Ulcerative Colitis

Treatments: Drug: Infliximab

Study type: Observational

Funder types: Other

Identifiers

NCT03765450

RP1713

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

18 participants in 1 patient group

Single Group Study

Description:

Patients with Acute Severe Ulcerative Colitis who are either a) biologic-naïve or b) biologic-experienced without a known history of anti-infliximab antibodies requiring infliximab infusion therapy as a part of standard of care.

Treatment:

Drug: Infliximab