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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03765450
Recruitment Status : Recruiting
First Posted : December 5, 2018
Last Update Posted : July 20, 2021
Information provided by (Responsible Party):
Alimentiv Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment
Ulcerative Colitis Drug: Infliximab

Detailed 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.

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Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pharmacokinetics of Infliximab and Tumor Necrosis Factor Concentrations in Serum, Stool, and Colonic Mucosa in Acute Severe Ulcerative Colitis
Actual Study Start Date : December 21, 2018
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Infliximab

Group/Cohort Intervention/treatment
Single Group Study
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.
Drug: Infliximab
Patients will receive infliximab at the discretion of their physician as part of standard of care.

Primary Outcome Measures :
  1. Inter-compartmental Difference in Infliximab Concentration [ Time Frame: 22 weeks ]
    Infliximab population pharmacokinetics

Secondary Outcome Measures :
  1. Change in Proteome [ Time Frame: 22 weeks ]
    Change in Proteomics before and after therapy

  2. Change in Transcriptome [ Time Frame: 22 weeks ]
    Change in Transcriptomics before and after therapy

  3. Change in Robarts Histopathologic Index [ Time Frame: 22 weeks ]
    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).

  4. Change in Mayo Clinic Endoscopic Score [ Time Frame: 22 weeks ]

    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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients diagnosed with acute severe ulcerative colitis, who are biologic-naive or biologic-experienced without a known history of anti-infliximab antibodies and will be receiving infliximab infusion therapy.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03765450

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Contact: Ana Olteanu 226 270 7868

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United States, California
UCSD Recruiting
San Diego, California, United States, 92037
Contact: Jennifer Neill   
Contact: Christina Chickering   
Principal Investigator: William Sandborn         
United States, New York
Cornell University Recruiting
New York, New York, United States, 10065
Contact: Robert Battat         
Principal Investigator: Robert Battat, MD         
Canada, Ontario
London Health Sciences Center Recruiting
London, Ontario, Canada, N6A 5A5
Contact: Tricia Leavens   
Contact: Heather Prins   
Principal Investigator: Vipul Jairath         
Mount Sinai Hospital Recruiting
Toronto, Ontario, Canada, M5G 1X5
Contact: Joanne Stempak   
Principal Investigator: Adam Weizman         
Principal Investigator: Mark Silverberg         
Sponsors and Collaborators
Alimentiv Inc.
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Study Director: Niels Vande Casteele UCSD
Govani SM, Waljee AK, Stidham RW, et al. Accelerated dosing of infliximab prevents colectomy within 90 days in only half of patients with severe ulcerative colitis [abstract]. Gastroenterology. 2016;150:S106. Abstract no. 516.
Al Khoury A, Chao C-y, Bessissow T, et al. Intensified infliximab rescue therapy for acute severe ulcerative colitis does not improve long term colectomy-free survival [abstract]. Gastroenterology. 2017;152:S399. Abstract no. P495.
Choy MC, Seah D, Gorelik A, et al. Comparison of accelerated infliximab induction vs standard induction treatment in acute severe ulcerative colitis [abstract]. Gastroenterology. 2016;150:S803. Abstract no. Mo1878.
Kevans D, Murthy S, Iacono A, et al. Accelerated clearance of serum infliximab during induction therapy for acute ulcerative colitis is associated with treatment failure [abstract]. Gastroenterology. 2012;142:S-384-S-385. Abstract no. Sa2031
Brandse JF, Wildenberg M, De Bruyn JR, et al. Fecal loss of infliximab as a cause of lack of response in severe inflammatory bowel disease [abstract]. Gastroenterology. 2013;1:S36. Abstract no. 157.

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Responsible Party: Alimentiv Inc. Identifier: NCT03765450    
Other Study ID Numbers: RP1713
First Posted: December 5, 2018    Key Record Dates
Last Update Posted: July 20, 2021
Last Verified: July 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alimentiv Inc.:
Optimal Dose
Optimal Frequency
Theraputic Drug Monitoring
Additional relevant MeSH terms:
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Colitis, Ulcerative
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Dermatologic Agents
Gastrointestinal Agents
Antirheumatic Agents