Trichuris Suis Ova Treatment in Left-sided Ulcerative Colitis

Colitis, Ulcerative Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01953354
• Other study ID #: DAIT AUC02
• Status: Terminated
• Phase: Phase 2
• First received: September 24, 2013
• Last updated: March 3, 2016
• Start date: November 2013
• Est. completion date: November 2015

Study information

• Verified date: March 2016
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer

Intervention

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)
• 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)

Locations

Country	Name	City	State
United States	University of Maryland	Baltimore	Maryland
United States	Tufts Medical Center	Boston	Massachusetts
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	University of Iowa Hospital	Iowa City	Iowa
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Vanderbilt University	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Weill Cornell Medical College	New York	New York
United States	Stanford University School of Medicine	Palo Alto	California
United States	Drexel University	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Virginia Mason Medical Center	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Autoimmunity Centers of Excellence, Coronado Biosciences, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (3)

Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007 May 12;369(9573):1627-40. Review. — View Citation

Moreels TG, Pelckmans PA. Gastrointestinal parasites: potential therapy for refractory inflammatory bowel diseases. Inflamm Bowel Dis. 2005 Feb;11(2):178-84. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects who Achieve a Clinical Response	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.	12 Weeks	Yes
Secondary	Percentage of Subjects Achieving Remission	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.	12 Weeks	Yes
Secondary	Percentage of Subjects with Healed Colonic Tissue	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.	12 Weeks	Yes
Secondary	Time to Reach a Modified Clinical Response	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).	Up to 12 Weeks	Yes
Secondary	Percentage of Subjects with Colonoscopic Evidence of a Visible Worm (luminal or attached)		Baseline to Week 36	No
Secondary	Percentage of Subjects with Increase in Diarrhea	The percentage of subjects experiencing an increase in diarrhea, as measured by the Mayo Score's Stool Frequency score.	Baseline to Week 36	Yes
Secondary	Percentage of Subjects Requiring Increased Medications to Treat UC	Percentage of subjects who require dose-escalation of concurrent medications or need rescue medications to treat UC.	Baseline to Week 36	Yes

External Links

•   Autoimmunity Centers of Excellence (ACE)
•   National Institute of Allergy and Infectious Diseases (NIAID)