Evaluation of an Oral Anti-TNF Antibody in Patients With Active Ulcerative Colitis

March 4, 2014 updated by: Avaxia Biologics, Incorporated

A Multicenter, Double-Blind, Placebo-Controlled, Ascending-Dose, Repeat-Dose Safety and Pharmacokinetic Investigation of a Delayed-Release, Enteric-Coated Capsule Formulation of AVX 470 [Anti-TNF (Tumor Necrosis Factor) Globulin (Bovine)] in Patients With Active Ulcerative Colitis

The purpose of this study is to evaluate the safety and tolerability as well as the pharmacodynamic effects of multiple doses of AVX-470 administered orally in patients with active ulcerative colitis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

There is a significant unmet medical need for effective oral pharmacologic therapies for inflammatory bowel diseases such as ulcerative colitis. Current anti-TNF therapies, including infliximab and adalimumab, are effective treatments for these conditions, but they must be administered by intravenous or subcutaneous injection. The major safety concerns associated with the use of injectable anti-TNF therapies are infection, demyelinating disease, and lymphoma, all of which are the result of systemic exposure. These uncommon but serious side effects have limited the use of systemic anti-TNF antibody therapy to patients with severe disease that have failed to respond to first-line treatments.

AVX-470 is purified immunoglobulin (Ig) from the colostrum (early milk) of cows immunized with recombinant human tumor necrosis factor (rhTNF). AVX-470 is formulated in delayed-release enteric-coated capsules designed to protect the capsule contents from gastric acids following oral administration and to provide localized delivery to sites of inflammation in the distal intestine. Prior clinical experience with bovine Ig therapies in other human diseases suggests that AVX-470 will not be absorbed to any significant extent, meaning that systemic exposure could be minimized. The development of oral anti-TNF therapy targeting local intestinal disease activity might reduce the risks associated with injectable anti-TNF therapy and allow the convenience of oral dosing.

The present study is a first-in-human, Phase 1 clinical study. It is primarily intended to evaluate the safety and tolerability of multiple doses of AVX-470 administered orally to patients with active ulcerative colitis.

Animal models of ulcerative colitis using a mouse-specific TNF antibody derived from bovine colostrum demonstrated a 50% or more reduction in tissue TNF, TNF-messenger ribonucleic acid (mRNA), interleukin (IL)-6 mRNA, and myeloperoxidase and lowering of colonic inflammatory activity. Twenty-eight-day toxicology studies demonstrated no clinical or histologic findings in exposures above the intended clinical dose range.

Study Type

Interventional

Enrollment (Actual)

33

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Gent, Belgium, 9000
        • Gastro-enterologie
      • Leuven, Belgium, 3000
        • Gastro-enterologie
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2C8
        • The Northern Alberta Clinical Trials and Research Centre
    • Ontario
      • Toronto, Ontario, Canada, L4L 4Y7
        • Toronto Digestive Disease Associates
  • Hungary
      • Budapest, Hungary, 1083
        • Semmelweis Egyetem
      • Debrecen, Hungary, 4032
        • Debreceni Egyetem Orvos- és Egészségtudományi Centrum
      • Debrecen, Hungary, 4043
        • Kenézy Kórház Rendelőintézet Egészségügyi Szolgáltató Kft.
  • United States
    • California
      • Anaheim, California, United States, 92801
        • Anaheim Clinical Trials
    • Colorado
      • Lakewood, Colorado, United States, 80215
        • Rocky Mountain Gastroenterology Associates
    • Florida
      • Winter Park, Florida, United States, 327789
        • Shafran Gastroenterology Center
    • Maryland
      • Chevy Chase, Maryland, United States, 20815
        • Chevy Chase Clinical Research
    • Michigan
      • Chesterfield, Michigan, United States, 48047
        • Clinical Research Institute of Michigan
    • Missouri
      • Mexico, Missouri, United States, 65265
        • Center for Digestive and Liver Disease
    • Ohio
      • Columbus, Ohio, United States, 43215
        • Remington-Davis, Inc.
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma Foundation for Digestive Research
    • Tennessee
      • Nashville, Tennessee, United States, 37205
        • Nashville Medical Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Men or women aged 18 75, inclusive
  • Established diagnosis of ulcerative colitis involving the sigmoid colon or proximal segments of bowel
  • Total Mayo score between 5-12, inclusive, with endoscopic subscore of the Mayo score ≥ 2 and > 15 cm of involvement beyond the anal verge

Exclusion Criteria:

  • Women with a positive pregnancy test, who are breastfeeding, or who intend to become pregnant during the course of the study
  • Diagnosis of Crohn's disease, microscopic colitis or indeterminate colitis
  • Presence of ileostomy or colostomy, or history of prior colon resection
  • Patients with planned hospitalization or surgery during the course of the study
  • Known allergy to milk proteins, red meat or cornstarch
  • Stools positive for enteric infection, including parasitic, or C. difficile toxin within 28 days of screening
  • Documented presence of Hetatitis B (HBsAg), Hepatitis C (HCV), or HIV
  • Presence of dysplasia of any grade on colonoscopic biopsies
  • Treatment for cancer (excluding non-melanomatous cancer of the skin or cervical carcinoma in situ) or lymphoproliferative disorder (including lymphoma) within 5 years
  • History of tuberculosis (TB) or Listeria infection, or known exposure to another person with active TB disease within 12 weeks of screening; or history of past or current infection with different opportunistic infections
  • History of TNF inhibitor (infliximab, adalimumab or certolizumab pegol) use with primary treatment failure. Secondary treatment failures due to intolerance, allergic reaction, or loss of response will not constitute a basis for exclusion. Oral immunosuppressives, mesalamine, and corticosteroids (up to 20mg of prednisone per day) will be permitted so long as these medications are stable for defined periods of time before study participation commences.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: AVX 470
AVX 470 0.2 g(Cohort 1), 1.6 g (Cohort 2) and 3.5 g (Cohort 3) will be administered daily for 28 days
Drug: AVX 470
active comparator
Placebo Comparator: Placebo
Placebo will be administered daily for 28 days as a comparator with AVX-470 (all dose groups)
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability of AVX-470 over 28 days of treatment
Time Frame: 5 weeks
Assessments weekly during treatment and 1 week post treatment
5 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetics (serum, stool and gastrointestinal mucosal tissue levels) of AVX-470
Time Frame: 4 weeks
4 weeks
Measure the induction of or change in a human anti-bovine immunoglobulin antibody (HABA) response to AVX 470
Time Frame: 4 weeks
4 weeks

Other Outcome Measures

Outcome Measure
Time Frame
Clinical response to AVX 470 in ulcerative colitis, as assessed by the total Mayo score and subscores, after 28 days of treatment compared to Baseline
Time Frame: 4 weeks
4 weeks
Effect of AVX 470 on endoscopic healing in ulcerative colitis, as assessed by the endoscopic subscore of the total Mayo score and the Ulcerative Colitis Index of Severity (UCEIS), after 28 days of treatment compared to Baseline
Time Frame: 4 weeks
4 weeks
Evaluate the effects of AVX 470 on biomarkers of ulcerative colitis activity over 28 days of treatment compared to Baseline
Time Frame: 4 weeks
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Avaxia Biologics, Incorporated

Investigators

  • Study Director: Scott Harris, MD, Avaxia Biologics, Incorporated

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2013

Primary Completion (Actual)

December 1, 2013

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

December 24, 2012

First Submitted That Met QC Criteria

December 24, 2012

First Posted (Estimate)

January 2, 2013

Study Record Updates

Last Update Posted (Estimate)

March 5, 2014

Last Update Submitted That Met QC Criteria

March 4, 2014

Last Verified

February 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AB1101
  • 2012-004850-27 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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