Trichuris Suis Ova Treatment in Left-sided Ulcerative Colitis

Phase 2

Terminated

• Conditions: Colitis, Ulcerative
• Interventions: Biological: Placebo; Biological: Trichuris suis ova (TSO)

• Registration Number: NCT01953354
• Lead Sponsor: 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.

Study Timeline

• Study First Submitted: 2013-09-24
• Study First Submitted QC: 2013-09-24
• Study First Posted: 2013-10-01
• Study Start: 2013-11
• Primary Completion: 2015-11
• Study Completion: 2015-11
• Results First Submitted: 2016-12-16
• Results First Submitted QC: 2016-12-16
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-09
• Results First Posted: 2017-02-10
• Last Update Posted: 2017-03-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 16

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Six doses of TSO placebo orally over a ten-week period
Trichuris suis ova (TSO)	Trichuris suis ova (TSO)	Six doses of TSO orally over a ten-week period

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved a Clinical Response at Week 12	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

Name	Time	Method
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	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.
Percent of Participants With Increase in Diarrhea	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.
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.	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.
Percent of Participants With Healed Colonic Mucosa at Week 12	Week 12	Healed colonic mucosa is defined as a Mayo endoscopy score of 0 or 1.
Percent of Participants Who Achieved Remission at Week 12	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.
Percent of Participants With Colonoscopic Evidence of Visible Worm	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.
Percent of Participants With Increase in Concurrent Ulcerative Colitis (UC) Medications or New Rescue Medications Added	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.

Trial Locations

Locations (17)

University of Chicago; 🇺🇸 Chicago, Illinois, United States

University of Miami Miller School of Medicine; 🇺🇸 Miami, Florida, United States

University of Maryland; 🇺🇸 Baltimore, Maryland, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Iowa Hospital; 🇺🇸 Iowa City, Iowa, United States

Virginia Mason Medical Center; 🇺🇸 Seattle, Washington, United States

Vanderbilt University; 🇺🇸 Nashville, Tennessee, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Northwestern University Feinberg School of Medicine; 🇺🇸 Chicago, Illinois, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Stanford University School of Medicine; 🇺🇸 Palo Alto, California, United States

Weill Cornell Medical College; 🇺🇸 New York, New York, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

Drexel University; 🇺🇸 Philadelphia, Pennsylvania, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States