Trichuris Suis Ova Treatment in Left-sided Ulcerative Colitis

• ClinicalTrials.gov Identifier: NCT01953354
• Recruitment Status: Terminated
• First Posted: October 1, 2013
• Results First Posted: February 10, 2017
• Last Update Posted: March 17, 2017
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Coronado Biosciences, Inc.; Autoimmunity Centers of Excellence
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Colitis, Ulcerative	Biological: Trichuris suis ova (TSO); Biological: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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
• Study Start Date: November 2013
• Actual Primary Completion Date: November 2015
• Actual Study Completion Date: November 2015

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Who Achieved a Clinical Response at Week 12 [ Time Frame: Week 12 ]
   Clinical response is defined as a reduction in the Mayo score of at least 3 points and at least a 30% reduction from Baseline, along with either a decrease from Baseline in the rectal bleeding subscore of more than 1 point or a rectal bleeding subscore of 0 or 1.

Secondary Outcome Measures :

1. Percent of Participants Who Achieved Remission at Week 12 [ Time Frame: Week 12 ]
   Remission is defined as a Mayo score of less than or equal to 1 with absence of rectal bleeding and endoscopy score of 0 or 1.
2. Percent of Participants With Healed Colonic Mucosa at Week 12 [ Time Frame: Week 12 ]
   Healed colonic mucosa is defined as a Mayo endoscopy score of 0 or 1.
3. Percent of Participants With a Modified Clinical Response [ Time Frame: From Day 0 through time of first clinical response or end of follow-up, whichever comes first, up to 12 Weeks ]
   Modified clinical response is defined as a reduction in the modified Mayo score (i.e., minus the endoscopy component) of at least 2 points from baseline.
4. Time to Modified Clinical Response [ Time Frame: From Baseline through the day that modified clinical response is reached. Week 16 is the last visit that the modified Mayo score is assessed. ]
   Number of days to reach a modified clinical response. Modified clinical response is defined as a reduction in the modified Mayo score (i.e., minus the endoscopy component) of at least 2 points from baseline.
5. Percent of Participants With Colonoscopic Evidence of Visible Worm [ Time Frame: From Day 0 through end of follow-up, up to 36 weeks ]
   Stool evaluations for ova and parasites confirmed the absence of T. suis. If evidence suggested a presence of T. suis, a colonoscopy would be performed to confirm invasion with a visible worm.
6. Percent of Participants With Increase in Diarrhea [ Time Frame: From Day 0 through end of follow-up, up to 36 weeks ]
   An increase in diarrhea is defined as an increase in the Mayo Score's Stool Frequency score by at least 1 point from baseline at any time during follow-up.
7. Percent of Participants With Increase in Concurrent Ulcerative Colitis (UC) Medications or New Rescue Medications Added [ Time Frame: From Day 0 through Week 16 ]
   New or increase in UC medications is defined as a need for dose-escalation of concurrent medications or need for rescue medications to treat UC through Week 16.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

National Institute of Allergy and Infectious Diseases (NIAID)

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:

National Institute of Allergy and Infectious Diseases (NIAID) website 

Autoimmunity Centers of Excellence (ACE) website 

Publications:

Summers RW, Elliott DE, Qadir K, Urban JF Jr, Thompson R, Weinstock JV. Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am J Gastroenterol. 2003 Sep;98(9):2034-41. doi: 10.1111/j.1572-0241.2003.07660.x.

Moreels TG, Pelckmans PA. Gastrointestinal parasites: potential therapy for refractory inflammatory bowel diseases. Inflamm Bowel Dis. 2005 Feb;11(2):178-84. doi: 10.1097/00054725-200502000-00012.

Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007 May 12;369(9573):1627-40. doi: 10.1016/S0140-6736(07)60750-8.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01953354
• Other Study ID Numbers: DAIT AUC02
• First Posted: October 1, 2013
• Results First Posted: February 10, 2017
• Last Update Posted: March 17, 2017
• Last Verified: February 2017

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; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Pathologic Processes; Inflammatory Bowel Diseases