Trichuris Suis Ova Treatment in Left-sided Ulcerative Colitis

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Coronado Biosciences, Inc.
Autoimmunity Centers of Excellence
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01953354
First received: September 24, 2013
Last updated: April 27, 2015
Last verified: April 2015
  Purpose

The purpose of this study is to evaluate the safety and effectiveness of trichuris suis ova (TSO) in ulcerative colitis (UC). We will look at how TSO affects the body's immune response and if there are related changes in participants' UC.


Condition Intervention Phase
Colitis, Ulcerative
Biological: Trichuris suis ova (TSO)
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Double-blind, Placebo-controlled Phase II Clinical Study of Trichuris Suis Ova Treatment in Left-sided Ulcerative Colitis and Its Effects on Mucosal Immune State and Microbiota

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Percentage of Subjects who Achieve a Clinical Response [ Time Frame: 12 Weeks ] [ Designated as safety issue: Yes ]
    Clinical response will be defined as a reduction in Mayo score of >/= 3 and >/= 30% reduction from baseline, along with either a decrease from baseline in rectal bleeding sub-score of > 1 point or absolute rectal bleeding score of 0 or 1.


Secondary Outcome Measures:
  • Percentage of Subjects Achieving Remission [ Time Frame: 12 Weeks ] [ Designated as safety issue: Yes ]
    Percentage of subjects in each study arm who achieve a remission at Week 12, where remission is defined as Mayo score of <\= 1 with absence of rectal bleeding and endoscopy score of 0 or 1.

  • Percentage of Subjects with Healed Colonic Tissue [ Time Frame: 12 Weeks ] [ Designated as safety issue: Yes ]
    Percentage of subjects in each study arm with healed colonic mucosa at Week 12, where healed colonic mucosa is defined as a Mayo endoscopy score of 0 or 1.

  • Time to Reach a Modified Clinical Response [ Time Frame: Up to 12 Weeks ] [ Designated as safety issue: Yes ]
    Time to reach a modified clinical response, where modified clinical response is defined as a reduction in the modified Mayo score of >/= 2 from baseline (i.e., minus the endoscopy component).

  • Percentage of Subjects with Colonoscopic Evidence of a Visible Worm (luminal or attached) [ Time Frame: Baseline to Week 36 ] [ Designated as safety issue: No ]
  • Percentage of Subjects with Increase in Diarrhea [ Time Frame: Baseline to Week 36 ] [ Designated as safety issue: Yes ]
    The percentage of subjects experiencing an increase in diarrhea, as measured by the Mayo Score's Stool Frequency score.

  • Percentage of Subjects Requiring Increased Medications to Treat UC [ Time Frame: Baseline to Week 36 ] [ Designated as safety issue: Yes ]
    Percentage of subjects who require dose-escalation of concurrent medications or need rescue medications to treat UC.


Enrollment: 16
Study Start Date: November 2013
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trichuris suis ova (TSO)
Six doses of TSO orally over a ten-week period
Biological: Trichuris suis ova (TSO)
Six doses of TSO orally over a ten-week period (e.g., every 2 weeks x 10 weeks for a total of 6 total doses)
Other Names:
  • T. suis ova
  • 7500 Trichuris suis ova (7500 TSO )
  • CNDO 201
Placebo Comparator: Placebo
Six doses of TSO placebo orally over a ten-week period
Biological: Placebo
Six doses of TSO placebo orally over a ten-week period (e.g., every 2 weeks x 10 weeks for a total of 6 total doses)
Other Name: Trichuris suis ova (TSO) placebo

Detailed Description:

The cause of UC, an inflammatory bowel disease (IBD), is not well understood. It is believed to be caused from an abnormal immune response to the normal bacteria that live in the gut (intestines and colon). This response acts as an "attack" on the healthy tissue of the bowel by a person's own immune cells which leads to disease.

It is well known that autoimmune diseases such as IBD, asthma, diabetes, and multiple sclerosis are more common in industrialized, well-developed countries with better sanitation and hygiene, as in the United States. These "cleaner" environments reduce exposure to germs and parasites naturally found in the environment. This reduced exposure may trigger responses in the body that make people more prone to diseases such as UC. People in non-industrialized countries and the tropics, where parasites are common, rarely develop these diseases. This observation has led researchers to want to better understand the relationship between the lack of natural bacteria in the gut and the onset of autoimmune diseases like as UC.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject has provided written informed consent
  2. Diagnosis of UC (newly diagnosed or established patients) as determined by medical history, endoscopic and histological confirmation with the proximal disease extent limited to the left colon (distal to the splenic flexure), and accessible by flexible sigmoidoscopy. Patients with left-sided disease and the presence of a periappendiceal red patch (limited cecal inflammation) will be eligible as long as there is no intervening evidence of colitis between the cecal base and the upper boundary of inflammation in the left colon.
  3. Mayo score >/= 4, as scored at Screen 2
  4. If taking the following medications at Screen 1, subjects must meet the following criteria:

    1. Oral Corticosteroids: stable treatment for at least 4 weeks prior to Day 0 with a maximum dose equivalent to <\=15 mg/day of prednisone
    2. Immunosuppressants (azathioprine (AZA) or 6-mercaptopurine (6-MP)): treatment for at least 12 weeks with a stable dose, not exceeding 2.5 mg/kg/day of AZA or 1.5 mg/kg/day of 6-MP, during the 4 weeks prior to Day 0
    3. Aminosalicylates: stable oral doses up to 4.8 g/day for at least 4 weeks prior to Day 0.

Exclusion Criteria:

  1. Subjects whose UC is anticipated to require surgical, endoscopic, or radiologic intervention during study participation
  2. Uncontrolled GI bleeding
  3. Subjects who have disease limited to the rectum (maximum disease extent of less than 15 cm)
  4. Women who are pregnant, breast-feeding, or planning to become pregnant during the study. All women of childbearing potential must have a negative serum pregnancy test at Screen 2 prior to randomization of treatment.
  5. Women of childbearing potential not using adequate birth control measures (e.g., total abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization, Depo-Provera, or hormonal implants).
  6. Current or recent serious systemic disorder including clinically significant impairment in cardiac, pulmonary, liver, renal, endocrine, hematologic, or neurologic function, based on investigator discretion
  7. Subjects currently receiving the following concomitant medications:

    1. Prednisone or its equivalent at unstable doses or at doses exceeding 15 mg/day within 4 weeks prior to Day 0
    2. Local steroids such as budesonide, Colifoam, or Predsol enemas within 2 weeks prior to Screen 2
    3. Topical therapies, either mesalamine or steroids, taken within 2 weeks of Screen 2
    4. Non-steroidal anti-inflammatory drugs (NSAIDs), Cyclooxygenase (COX)-2 inhibitors, or aspirin >100 mg/day within 2 weeks prior to Screen 2
    5. Tumor necrosis factor (TNF)-alpha inhibitors including but not limited to infliximab (Remicade) or adalimumab (Humira) within 12 weeks of Day 0
    6. Any biological agent within 12 weeks of Day 0
    7. Metronidazole within 4 weeks of Day 0
    8. Receipt of any investigational agent within the 12 weeks prior to Day 0
    9. Antibacterial or oral antifungal agents within 4 weeks of Screen 2
    10. Interferon (IFN) therapy
    11. Anticoagulants
    12. Methotrexate
  8. Blood transfusion within the 12 weeks prior to Day 0
  9. Presence of any of the following abnormal laboratory parameters at Screen 1:

    1. Hemoglobin < 10.0 g/dL
    2. White Blood Count (WBC) < 4,000 or > 20,000/L (equivalent to WBC < 4 or > 20 x109/L)
    3. Platelets < 100,000 or > 800,000/L (equivalent to platelets < 100 or > 800 x109/L)
    4. Total bilirubin > 1.5 × Upper limit of normal (ULN)
    5. Alanine transaminase (ALT) > 2 × ULN
    6. Aspartate transaminase (AST) > 2 × ULN
    7. Alkaline phosphatase (ALK) > 1.5 × ULN
    8. Gamma-glutamyl transferase (GGT) > 1.5 × ULN
    9. Creatinine > 1.5 × ULN
  10. History of drug or alcohol abuse within one year prior to Day 0
  11. Inability to understand the nature and requirements of the study, or to comply with the study procedures or planned schedule of study visits
  12. Evidence of infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
  13. Active infection with C. difficile, bacterial enteric pathogens, or pathogenic ova/parasites
  14. History of malignancy within the last 5 years, except for resected basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ cervical cancer Grade I
  15. History of colonic dysplasia
  16. Any social or medical condition that, in the opinion of the investigator, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01953354

Locations
United States, California
Stanford University School of Medicine
Palo Alto, California, United States, 94305
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06510
United States, Florida
University of Miami Miller School of Medicine
Miami, Florida, United States, 33136
United States, Illinois
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
University of Chicago
Chicago, Illinois, United States, 60637
United States, Iowa
University of Iowa Hospital
Iowa City, Iowa, United States, 52242
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10021
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Drexel University
Philadelphia, Pennsylvania, United States, 19103
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37212
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Virginia Mason Medical Center
Seattle, Washington, United States, 98101
Sponsors and Collaborators
Coronado Biosciences, Inc.
Autoimmunity Centers of Excellence
Investigators
Study Chair: Stephen Hanauer, MD Northwestern University
Study Chair: Bana Jabri, MD, PhD University of Chicago
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01953354     History of Changes
Other Study ID Numbers: DAIT AUC02
Study First Received: September 24, 2013
Last Updated: April 27, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Ulcerative colitis (UC)
Inflammatory Bowel Disease (IBD)
Trichuris suis ova (TSO)

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

ClinicalTrials.gov processed this record on July 29, 2015