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Center for Global Research Data

Early changes in inflammatory biomarkers and long-term outcomes in patients with IBD: A pooled post-hoc analyses of clinical trials

Lead Investigator: Siddharth Singh, University of California, San Diego
Title of Proposal Research: Early changes in inflammatory biomarkers and long-term outcomes in patients with IBD: A pooled post-hoc analyses of clinical trials
Vivli Data Request: 4931
Funding Source: None
Potential Conflicts of Interest: Research grant from AbbVie and Janssen
In the last 2 years, consulting for Takeda (completed in 12/2018) and ad-hoc honorarium for Pfizer for grant review (most recently in 06/2020)
We will not be comparing medications from these trials.

Summary of the Proposed Research:

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC) are lifelong, debilitating autoimmune diseases affecting the small and large intestines, causing abdominal pain, diarrhea, bleeding and weight loss. The disease is characterized by ulceration and inflammation in the intestines, seen on endoscopy. Globally, the incidence and prevalence of IBD is rising, affecting approximately 2 million Americans. The disease frequently results in hospitalization and surgery, and requires treatment with potentially toxic and expensive immunosuppressive therapies.

Disease monitoring is an integral part of management in patients with IBD, partly because symptoms may not accurately correlate with active inflammation. Currently, endoscopy is the gold standard for monitoring inflammation, but this test is invasive, expensive and requires sedation, and is difficult to perform repeatedly. Non-invasive blood and stool markers of inflammation such as C-reactive protein and stool calprotectin may serve as potential substitutes for monitoring inflammation. In particular, how these biomarkers change over time in patients on treatment may predict long-term clinical outcomes such as risk of relapse, surgery and disease-related complications. Since these are non-invasive, they can be performed repeatedly. However, there is limited understanding of how these biomarkers change during treatment and if there are specific thresholds to consider when these tests are used for monitoring for predicting long-term disease outcomes. Hence, we propose to study patterns of dynamic changes in biomarkers of inflammation early during intervention, and identify whether there might be thresholds (both absolute, and relative change from baseline) in biomarkers that may help identify patients at higher vs. lower likelihood of superior outcomes.

This will be directly relevant to clinical practice, allowing early, effective, efficient monitoring and facilitating early treatment modification in patients who do not achieve early thresholds.

Requested Studies:

A Phase II Study of the Human Anti-TNF Antibody Adalimumab for the Induction of Clinical Remission in Subjects With Crohn’s Disease
Sponsor: AbbVie
Study ID: NCT00055523
Sponsor ID: M02-403

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction of Clinical Remission in Subjects With Moderate to Severe Crohn’s Disease Who Have Lost Response or Are Intolerant to Infliximab
Sponsor: AbbVie
Study ID: NCT00105300
Sponsor ID: M04-691

A Multi Center, Open Label Study of the Human Anti TNF Monoclonal Antibody Adalimumab to Evaluate the Long Term Safety and Tolerability of Repeated Administration of Adalimumab in Subjects With Crohn’s Disease
Sponsor: AbbVie
Study ID: NCT00195715
Sponsor ID: M04-690

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab Endoscopy Trial to Evaluate the Effects on Mucosal Healing in Subjects With Crohn’s Disease Involving the Colon
Sponsor: AbbVie
Study ID: NCT00348283
Sponsor ID: M05-769

A Multi-Center, Double-Blind Study to Evaluate the Safety, Efficacy and Pharmacokinetics of the Human Anti-TNF Monoclonal Antibody Adalimumab in Pediatric Subjects With Moderate to Severe Crohn’s Disease
Sponsor: AbbVie
Study ID: NCT00409682
Sponsor ID: M06-806

A Multi-Center, Randomized, Double-blind, Placebo-controlled Study of Adalimumab for the Maintenance of Clinical Remission in Japanese Subjects With Crohn’s Disease
Sponsor: AbbVie
Study ID: NCT00445432
Sponsor ID: M06-837

A Multi-Center, Randomized, Double-blind, Placebo-controlled Study of Adalimumab for the Induction of Clinical Remission in Japanese Subjects With Crohn’s Disease
Sponsor: AbbVie
Study ID: NCT00445939
Sponsor ID: M04-729

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab (MLN0002) in Patients With Moderate to Severe Crohn’s Disease
Sponsor: Takeda
Study ID: NCT00783692
Sponsor ID: C13007

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction of Clinical Response and Remission by Vedolizumab in Patients With Moderate to Severe Crohn’s Disease
Sponsor: Takeda
Study ID: NCT01224171
Sponsor ID: C13011

An Open-Label, Multicenter, Efficacy and Safety Study to Evaluate Two Treatment Algorithms in Subjects With Moderate to Severe Crohn’s Disease
Sponsor: AbbVie
Study ID: NCT01235689
Sponsor ID: M11-271

A Multicenter Open-label Study of the Human Anti-TNF Monoclonal Antibody Adalimumab to Investigate Efficacy, Safety and Pharmacokinetics After Dose Escalation in Japanese Subjects With Crohn’s Disease
Sponsor: AbbVie
Study ID: NCT01958827
Sponsor ID: M13-687

A Phase 2, Randomized, Double-Blind, Multicenter Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Two Adalimumab Dosing Regimens in Chinese Subjects With Moderately to Severely Active Crohn’s Disease and Elevated High-Sensitivity C-reactive Protein
Sponsor: AbbVie
Study ID: NCT02015793
Sponsor ID: M14-232

A Multicenter, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Adalimumab for the Induction and Maintenance of Clinical Remission in Chinese Patients With Moderately to Severely Active Crohn’s Disease and Elevated High-Sensitivity C-reactive Protein
Sponsor: AbbVie
Study ID: NCT02499783
Sponsor ID: M14-233

Phase III, Multicenter, Randomized, Double-blinded, Placebo-controlled, Parallel-group Study to Examine the Efficacy, Safety, and Pharmacokinetics of Intravenous MLN0002 (300 mg) Infusion in Induction and Maintenance Therapy in Japanese Patients With Moderately or Severely Active Ulcerative Colitis
Sponsor: Takeda
Study ID: NCT02039505
Sponsor ID: MLN0002/CCT-101

An Open-Label Multicenter Study to Evaluate the Impact of Adalimumab on Quality of Life, Health Care Utilization and Costs of Ulcerative Colitis Subjects in the Usual Clinical Practice Setting
Sponsor: AbbVie
Study ID: NCT01550965
Sponsor ID: M13-045

A Phase 2, Randomized, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MLN0002 Following Multiple Intravenous Doses in Patients With Ulcerative Colitis
Sponsor: Takeda
Study ID: NCT01177228
Sponsor ID: C13002

A Multi-Center, Randomized, Double-Blind, Placebo-controlled Study of Adalimumab in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis.
Sponsor: AbbVie
Study ID: NCT00853099
Sponsor ID: M10-447

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by MLN0002 in Patients With Moderate to Severe Ulcerative Colitis
Sponsor: Takeda
Study ID: NCT00783718
Sponsor ID: C13006

Phase 2, Multiple Dose, Open-Label Study to Determine the Long Term Safety of MLN0002 in Patients With Ulcerative Colitis and Crohn’s Disease
Sponsor: Takeda
Study ID: NCT00619489
Sponsor ID: C13004

A Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction and Maintenance of Clinical Remission in Subjects With Moderately to Severely Active Ulcerative Colitis
Sponsor: AbbVie
Study ID: NCT00408629
Sponsor ID: M06-827

A Multicenter, Randomized, Double-blind Placebo-controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction of Clinical Remission in Subjects With Moderately to Severely Active Ulcerative Colitis
Sponsor: AbbVie
Study ID: NCT00385736
Sponsor ID: M06-826