Biomarkers to Predict and Monitor Response to Infliximab

Detection of Serum Protein Biomarkers to Predict and Monitor Response to Infliximab Using SOMAscan

The aim of the study is to generate novel minimally-invasive serum protein signatures and biomarkers in children and adolescents with Crohn's Disease (CD) that correlate with and can predict and monitor patients who will have a prolonged response to Infliximab so that personalized medicine can be applied to patients with CD.

Study Overview

• Status: Recruiting
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: Infliximab

Detailed Description

Prospective, observational study will enroll 120 unique pediatric Crohn's disease patients between the ages of 3-20 years among multiple sites. Patients will be naïve to TNF inhibitor. If patient is going to start infliximab or infliximab biosimilar, patient may be enrolled in study. Study length will be from commencement of infliximab until the infusion visit given at least 1 year after initiation. During the study, if the patient fails infliximab or biosimilar, they will be complete study once failure is indicated and discontinued on infliximab or biosimilar. Patients may be on concurrent IBD therapy such as antibiotics, mesalamines, immunomodulators and may continue in study if non-standard induction schedule or changes made during induction or maintenance to dose or frequency. Excluded patients will be those receiving infliximab or biosimilar infusions at home due to need for blood collection at time of infusion, on systemic corticosteroids (topical preparations such as budesonide are allowed), and those who have already undergone significant bowel surgery relating to their Crohn's.

Study visits will take place in conjunction with previously scheduled routine clinic visits or infusion visits. At initial study visit, demographics, medical and surgical history, PARIS classification, PCDAI, weight and height, fecal calprotectin, labs, EGD and colonoscopy report and pathology report, cross-sectional imaging reports and concurrent medications will be obtained and entered. Parameters measured at each study visit will include any obtained labs, weight and height, PARIS classification, PCDAI, infliximab dose (mg/kg) and dose interval. There will be four study visits throughout the course of 1 year after initiating infliximab. At these four visits, blood will be obtained in PAXgene tubes for RNA analysis and serum for banking for SOMAscan analysis.

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • MassGeneral for Children
      • Contact: Harland Winter, MD; Phone Number: 617-724-2004; Email: hwinter@partners.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 20 years (ADULT, CHILD)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients 3-20 years old diagnosed with Crohn's Disease starting infliximab

Description

Inclusion Criteria:

• Patients between the ages of 3-20 years old
• Patient starting infliximab or infliximab biosimilar,
• Patients naïve to TNF inhibitor

Exclusion Criteria:

• Patients receiving infliximab or biosimilar infusions at home
• Patients already undergone significant bowel surgery relating to their Crohn's.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Define pretreatment serum protein biomarkers that predict and monitor response to TNF inhibitors (Discovery Cohort)	Run 120 pediatric Crohn's patients' serum at baseline, week 14, and week 54 on SOMAscan; Develop predictor model for protein biomarkers that predict response from baseline serum	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify pathophysiological mechanisms associated with response or lack of response in patients receiving IFX using SOMAscan.	Identify pathophysiological mechanisms associated with response or lack of response in patients receiving IFX using SOMAscan.	2 years
Use systems biology to map out pathways activated in those patients at week 14 that have clinical and laboratory response to infliximab	Use systems biology to map out pathways activated in those patients at week 14 that have clinical and laboratory response to infliximab	2 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Crohn's and Colitis Foundation

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 18, 2019
• Primary Completion (ANTICIPATED): November 30, 2022
• Study Completion (ANTICIPATED): January 1, 2023

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: November 30, 2020
• First Posted (ACTUAL): December 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: 2019p002322

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No