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

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. Read our disclaimer for details. Identifier: NCT01759056
Recruitment Status : Completed
First Posted : January 2, 2013
Last Update Posted : March 5, 2014
Information provided by (Responsible Party):
Avaxia Biologics, Incorporated

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: AVX 470 Drug: Placebo Phase 1

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  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : February 2013
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

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

Primary Outcome Measures :
  1. Safety and tolerability of AVX-470 over 28 days of treatment [ Time Frame: 5 weeks ]
    Assessments weekly during treatment and 1 week post treatment

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

Other Outcome Measures:
  1. 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 ]
  2. 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 ]
  3. Evaluate the effects of AVX 470 on biomarkers of ulcerative colitis activity over 28 days of treatment compared to Baseline [ Time Frame: 4 weeks ]

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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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): NCT01759056

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

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Avaxia Biologics, Incorporated Identifier: NCT01759056     History of Changes
Other Study ID Numbers: AB1101
2012-004850-27 ( EudraCT Number )
First Posted: January 2, 2013    Key Record Dates
Last Update Posted: March 5, 2014
Last Verified: February 2014

Keywords provided by Avaxia Biologics, Incorporated:
Ulcerative colitis

Additional relevant MeSH terms:
Colitis, Ulcerative
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases