Trichuris Suis Ova Treatment in Left-sided Ulcerative Colitis

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

Sponsors

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator: Coronado Biosciences, Inc.
Autoimmunity Centers of Excellence

Source National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

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.

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.

Overall Status Terminated
Start Date November 2013
Completion Date November 2015
Primary Completion Date November 2015
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Percentage of Participants Who Achieved a Clinical Response at Week 12 Week 12
Secondary Outcome
Measure Time Frame
Percent of Participants Who Achieved Remission at Week 12 Week 12
Percent of Participants With Healed Colonic Mucosa at Week 12 Week 12
Percent of Participants With a Modified Clinical Response From Day 0 through time of first clinical response or end of follow-up, whichever comes first, up to 12 Weeks
Time to Modified Clinical Response From Baseline through the day that modified clinical response is reached. Week 16 is the last visit that the modified Mayo score is assessed.
Percent of Participants With Colonoscopic Evidence of Visible Worm From Day 0 through end of follow-up, up to 36 weeks
Percent of Participants With Increase in Diarrhea From Day 0 through end of follow-up, up to 36 weeks
Percent of Participants With Increase in Concurrent Ulcerative Colitis (UC) Medications or New Rescue Medications Added From Day 0 through Week 16
Enrollment 16
Condition
Intervention

Intervention Type: Biological

Intervention Name: Trichuris suis ova (TSO)

Description: 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)

Arm Group Label: Trichuris suis ova (TSO)

Intervention Type: Biological

Intervention Name: Placebo

Description: 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)

Arm Group Label: Placebo

Other Name: Trichuris suis ova (TSO) placebo

Eligibility

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Healthy Volunteers: No

Overall Official
Location
Facility:
Stanford University School of Medicine | Palo Alto, California, 94305, United States
Yale University | New Haven, Connecticut, 06510, United States
University of Miami Miller School of Medicine | Miami, Florida, 33136, United States
Northwestern University Feinberg School of Medicine | Chicago, Illinois, 60611, United States
University of Chicago | Chicago, Illinois, 60637, United States
University of Iowa Hospital | Iowa City, Iowa, 52242, United States
University of Maryland | Baltimore, Maryland, 21201, United States
Tufts Medical Center | Boston, Massachusetts, 02111, United States
Mayo Clinic | Rochester, Minnesota, 55905, United States
Weill Cornell Medical College | New York, New York, 10021, United States
Duke University Medical Center | Durham, North Carolina, 27710, United States
Cleveland Clinic | Cleveland, Ohio, 44195, United States
Drexel University | Philadelphia, Pennsylvania, 19103, United States
University of Pittsburgh | Pittsburgh, Pennsylvania, 15213, United States
Vanderbilt University | Nashville, Tennessee, 37212, United States
Baylor College of Medicine | Houston, Texas, 77030, United States
Virginia Mason Medical Center | Seattle, Washington, 98101, United States
Location Countries

United States

Verification Date

February 2017

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Trichuris suis ova (TSO)

Type: Experimental

Description: Six doses of TSO orally over a ten-week period

Label: Placebo

Type: Placebo Comparator

Description: Six doses of TSO placebo orally over a ten-week period

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double (Participant, Investigator)

Source: ClinicalTrials.gov