Mucosal Immunity of Ulcerative Colitis Patients Undergoing Therapy With Trichuris Suis Ova

The concept of helminthic therapy (using worms to treat diseases) is supported by
experiments in mouse models as well as several clinical studies. TSO, which are purified
eggs from the porcine whipworm Trichuris suis, are being investigated in clinical trials as
a potential therapeutic agent for the treatment of active Crohn's disease, relapsing
multiple sclerosis, peanut and tree nut allergy, and adults with autistic disorders.

The goal of this study is to understand the immune mechanisms activated in the human
gastrointestinal tract by treatment with TSO, which may lead to improvements in the symptoms
of ulcerative colitis (UC). TSO have been shown to have a clinical benefit on a subset of
patients with UC in a previous randomized placebo-controlled trial (Summers et al. 2005).
However, the mechanisms of action of TSO on the intestinal mucosa remain unclear.

We propose an exploratory 24-week mechanistic randomized double-blind placebo-controlled
crossover study of TSO in patients with established and active UC to better characterize
similarities and differences in the immune mechanisms of the intestinal mucosa in response
to TSO. We hypothesize that treatment with TSO will lead to an anti-inflammatory immune
response in some individuals with UC through an increase in intestinal mucus production and
modulation of Th1, Th2, Th17, and T-regulatory effector lymphocyte populations.

Inclusion Criteria:

- Subjects will be outpatients between the ages of 18 and 72.

- Subjects must have a biopsy-proven diagnosis of ulcerative colitis for greater than
three months.

- There should be evidence of active disease with a total Mayo score of 6 to 10 points
(scores range from 0 to 12, with higher scores indicating more severe disease
activity).

- There should be moderate (marked erythema, lack of vascular pattern, friability,
erosions) to severe (spontaneous bleeding, ulceration) active disease on colonoscopy
(Mayo endoscopic score of at least 2) at time of enrollment.

- Laboratory inclusion criteria will require a hemoglobin level of >9.0 g/dL, a white
blood count between 5,000 and 15,000/μL, a platelet count of >100,000μL, a blood urea
nitrogen < 40mg/dL, a serum creatinine of <2.0mg/dL, a total bilirubin < 2.5 mg/dL,
and an alkaline phosphatase of <250U/dL.

- Women will be required to have a negative urine pregnancy test and to practice birth
control.

- The following medications will be allowed and continued throughout the study: Oral or
rectal sulfasalazine, mesalamine, or mesalamine derivative (maintenance therapy of >
8 weeks, stable dose of > 4 weeks); Oral corticosteroid (prednisone, prednisolone, or
budesonide) at an equivalent dose of a maximum of 40mg daily prednisone (maintenance
therapy of >4 weeks, stable dose of > 2 weeks), azathioprine or 6-mercaptopurine
(maintenance therapy of > 8 weeks, stable dose of > 4 weeks).

- Subjects must have the ability to provide informed consent and be willing to keep all
scheduled appointments for the duration for the study period.

Exclusion Criteria:

- Inpatients, pregnant patients, patients with impaired cognition, patients with a
history of active substance abuse in the past six months, and children.

- Patients with a history of bowel surgery in the prior six months or who currently or
previously had an ileostomy or colostomy.

- Patients with active malignancy or treatment with anticancer drugs in the past 5
years, have a history of colorectal cancer or dysplasia, or a history of neoplasm of
the gastrointestinal tract.

- Female patients who are pregnant, breastfeeding, wishing to become pregnant during
study participation, or unwilling to use birth control.

- Patients with white blood count <5,000 or >15,000/mm3; platelet count <150,000 per
μl; or iron or vitamin B12 deficiency. Correction of lab exclusion is allowed
provided that medical condition is not deemed to put patient at risk and stability of
result is sustained for a minimum of 30 days.

- Patients with stools positive for enteric pathogens, ova, or parasites at Screening

- Patients with active hepatitis B virus or hepatitis C virus infection or have been
exposed to human immunodeficiency virus (HIV).

- Patients who have received an anti-tumor necrosis factor inhibitor (e.g. infliximab)
within 12 weeks prior to Screening

- Patients who have received antibiotic, antifungal or antiparasitic medication in the
last 2 weeks prior to Screening and/or would potentially require this during the
study treatment period.

- Patients with evidence of poor compliance with medical advice and instruction
including diet or medication.

- Patients who are unable or unwilling to swallow study medication suspension.

- Patients will be excluded if they have previously attempted helminthic therapy.

- There must not be evidence of fulminant colitis or a Mayo score of greater than 10

- Patients will be excluded if other clinically significant disease is present that
could interfere with protocol compliance or interpretation of the results.