Clinical trial NCT01953354: Trichuris Suis Ova Treatment in Left-sided Ulcerative Colitis
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colitis, Ulcerative
Keywords: Ulcerative colitis (UC)
Inflammatory Bowel Disease (IBD)
Trichuris suis ova (TSO)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Coronado Biosciences, Inc.
name: Autoimmunity Centers of Excellence
First posted: 2013-10-01
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Participants Who Achieved a Clinical Response at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Percent of Participants Who Achieved Remission at Week 12
timeFrame: Week 12
measure: Percent of Participants With Healed Colonic Mucosa at Week 12
timeFrame: Week 12
measure: Percent of Participants With a Modified Clinical Response
timeFrame: From Day 0 through time of first clinical response or end of follow-up, whichever comes first, up to 12 Weeks
measure: Time to Modified Clinical Response
timeFrame: From Baseline through the day that modified clinical response is reached. Week 16 is the last visit that the modified Mayo score is assessed.
measure: Percent of Participants With Colonoscopic Evidence of Visible Worm
timeFrame: From Day 0 through end of follow-up, up to 36 weeks
measure: Percent of Participants With Increase in Diarrhea
timeFrame: From Day 0 through end of follow-up, up to 36 weeks
measure: Percent of Participants With Increase in Concurrent Ulcerative Colitis (UC) Medications or New Rescue Medications Added
timeFrame: From Day 0 through Week 16
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospital
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Drexel University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
Study officials:
affiliation: Northwestern University
name: Stephen Hanauer, MD
role: STUDY_CHAIR
affiliation: University of Chicago
name: Bana Jabri, MD, PhD
role: STUDY_CHAIR
References:
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. doi: 10.1111/j.1572-0241.2003.07660.x.
citation: 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.
citation: 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.