Evaluate if Response to Infliximab or Adalimumab May be Regained With an Immunomodulator

NCT02413047 | Terminated Results

• 1 other identifier: 1502834262
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The immunogenicity of anti-tumor necrosis factor alpha (anti-TNF) therapy in inflammatory bowel disease (IBD) is an important cause of loss of response to therapy that may lead to escalation of dose or discontinuation of therapy. Antibodies may develop to infliximab (ATI) or to adalimumab (ATA) and cause this loss of response, also known as a secondary loss of response. An alternative approach is the addition of immunomodulator (IM) therapy to counteract the antibody response and regain efficacy of the biologic medication. The investigators' goal is to treat patients' who have lost response to adalimumab or infliximab with an immunomodulator with the goal of eliminating the circulating antibodies to the anti-TNF and restoring efficacy.

Conditions

Inflammatory Bowel Disease; Ulcerative Colitis; Crohn's Disease

Outcome Measures

Primary Outcomes (5)

• Harvey Bradshaw Index HBI: Decrease >3 Points or Remission Score<5

  The Harvey-Bradshaw index (HBI) is a simplified version of the CDAI to foster a systematic collection of clinical data related to Crohn's disease. The index considers five parameters, exclusively clinical; patient well-being, abdominal pain, number of liquid or soft stools, abdominal mass, and complications.

  4 months

• Therapeutic Trough Level for Infliximab is Defined as >3 and as > 5 for Adalimumab.

  Trough level is the lowest level of drug detected in a subject prior to next dose of medication

  4 months

• Ulcerative Colitis Clinical Score UCCS Decrease >3 Points or Remission Score <3

  UCCS is the ulcerative colitis clinical score which is based on disease activity. The score is based on bowel movements, blood in stool, overall well being, and global assessment.

  4 months

• Change Inflammatory Bowel Disease Questionnaire SIBDQ

  SIBDQ is the short inflammatory bowel disease questionnaire which is a health-related quality of life tool measuring physical, social, and emotional status.

  4 months

• Eliminate Antibodies: Threshold Levels for ATI is < 3.1and is < 1.7 for ADA.

  unwanted immunogenicity is an immune response by an organism against a therapeutic antigen. This reaction leads to production of anti-drug antibodies inactivating the therapeutic effects of the treatment.

  4 months

Secondary Outcomes (3)

• Improvement or Normalization of Mayo Endoscopy Score for UC Patients

  4 months

• Improvement or Normalization of C-reactive Protein, Sedimentation Rate and Fecal Calprotectin

  4 months

• Improvement or Normalization of the Simple Endoscopic Score-Crohn's Disease (SES-CD)

  4 months

Study Arms (1)

Immunomodulator

EXPERIMENTAL

Azathioprine, 6 mercaptopurine or methotrexate.

Drug: Azathioprine; Drug: 6 mercaptopurine; Drug: Methotrexate

Interventions

Azathioprine DRUG

Medication will be given in pill form to patients to take daily as long as the patient has not been intolerant to it in the past.

Also known as: Imuran

Immunomodulator

6 mercaptopurine DRUG

Medication will be given in pill form to patients to take daily as long as the patient has not been intolerant to it in the past as an alternative to imuran

Immunomodulator

Methotrexate DRUG

Medication will be given in subcutaneous injection form once a week if the patient cannot take imuran or 6 mercaptopurine.

Immunomodulator

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with inflammatory bowel disease who on are stable doses of infliximab or adalimumab for at least 3 months who experience a secondary loss of response to the medication based on clinical symptoms.
• Presence of at least one objective marker of active disease: active disease based on endoscopy, elevated fecal calprotectin or serologic markers of inflammation (C-reactive protein or sedimentation rate).
• Crohn's patients have a Harvey Bradshaw index \>5
• Ulcerative colitis patients have a Ulcerative Colitis Clinical Score \> 5
• Have an undetectable or inadequate trough level of infliximab or adalimumab and detectable ATI or ADA.
• Oral corticosteroid therapy is allowed. (prednisone at a stable dose ≤30 mg/day, budesonide at a stable dose ≤9 mg/day, or equivalent steroid) provided that the dose has been stable for the 4 weeks immediately prior to enrollment if corticosteroids have recently been initiated

You may not qualify if:

• Previous noncompliant with medications
• \< 18 years of age or \>80 years of age.
• Congestive heart failure
• Abnormal liver tests alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2 × the upper limit of normal (ULN) or leucopenia WBC count \<3 × 109/L
• Pregnant or planning on becoming pregnant.
• Active tuberculosis or hepatitis B infection
• Any cancer within the past 5 years. (Exception non-melanomatous skin cancer.)
• Receiving any immunomodulator therapy within the past 3 months
• Evidence of or treatment for C. difficile infection within 60 days or other intestinal pathogen within 30 days prior to enrollment
• Clinically significant extra-intestinal infection (e.g., pneumonia, pyelonephritis) within 30 days of the initial screening visit
• Any live vaccinations within 30 days prior to study drug administration except for the influenza vaccine
• Any identified congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, human immunodeficiency virus \[HIV\] infection, organ transplantation)
• Any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise patient safety
• Unable to give own informed consent

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana University Hospital

Indianapolis, Indiana, 46062, United States

Location

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease

Interventions

Azathioprine; Mercaptopurine; Methotrexate

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Aminopterin; Pterins; Pteridines

Limitations and Caveats

The study terminated early due to low subject enrollment. Since only 3 patients were enrolled, study analysis was not possible for measurable outcomes.

Results Point of Contact

• Title: Dr. Matthew Bohm, DO (Principal Investigator)
• Organization: Indiana University

mbohm@iu.edu

3179485136

Study Officials

• Matthew Bohm, DO

  IndianaU IRB

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: March 6, 2015
• First Posted: April 9, 2015
• Study Start: May 1, 2015
• Primary Completion: February 1, 2018
• Study Completion: February 1, 2018
• Last Updated: November 4, 2019
• Results First Posted: November 4, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)