Efficacy and Safety of Trichuris Suis Ova (TSO) as Compared to Placebo (TRUST-I)

This is a randomized, double-blind, placebo-controlled, multicenter, and proof of concept study with a parallel group design to evaluate the safety and efficacy of oral Trichuris Suis Ova (TSO) suspension, as compared to placebo, in patients with moderately to severely active Crohn's disease. This study will also have an optional open-label extension for patients completing the double-blind phase of the study.

• Biological: Trichuris suis ova (TSO)
  TSO 7500: 7500 embryonated, viable TSO every 2 weeks X 10 weeks (up to 6 total doses)
• Biological: Placebo
  Placebo: dose every 2 weeks X 10 weeks (up to 6 total doses)

• Placebo Comparator: Placebo
  Intervention: Biological: Placebo
• Experimental: TSO 7500
  Intervention: Biological: Trichuris suis ova (TSO)

Inclusion Criteria:

1. Patient is male or female, 18 to 65 years old.
2. Patient with established diagnosis of Crohn's disease (CD) for at least 3 months confirmed by endoscopic and histological, or endoscopic and radiological criteria.
3. Patient with localization of CD either in terminal ileum (L1), in colon (L2) or ileocolitis (L3), all without upper gastrointestinal involvement (- L4) according to the Montreal classification (2005).
4. Patient with active, symptomatic CD manifested by CDAI ≥ 220 and ≤ 450 at Baseline.
5. Patient with active intestinal inflammation as visualized by endoscopy within 8 weeks prior to Baseline.
6. Patient is not using concomitant medication for treatment of underlying Crohn's disease with the following exceptions: concomitant medications may include: 1) Oral or rectal sulfasalazine, mesalazine (5-ASA), or mesalazine derivative, if receiving it for >6 weeks and if receiving the same dose for at least 4 weeks; 2) Oral prednisone up to 15 mg/day, or budesonide if receiving it for >4 weeks and if receiving the same dose for at least 4 weeks; and 3) Azathioprine (up to 2.5 mg/kg daily) or 6-mercaptopurine (up to 2 mg/kg daily) if receiving it for >3 months and if receiving the same dose for at least 8 weeks prior to Baseline.
7. Hemoglobin of at least 10 g/dl, normal white blood cell and platelet count > lower limit of normal at screening.
8. For females of childbearing potential, negative serum pregnancy test prior to enrollment, not breastfeeding for study duration, and willingness to use accepted forms of reliable birth control for study duration [including bilateral tubal ligation, use of oral contraceptives, double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera®, hormonal implants, and total abstinence]. Pregnancy tests are not required (indicate "N/A") for males or females not of childbearing potential (post-menopausal with last menstrual period >1 year ago or total hysterectomy).
9. Patient has the ability to provide informed consent.

Exclusion Criteria:

1. Patient with known Crohn's lesions in the upper GI-tract (esophagus, stomach, duodenum, jejunum) with present symptoms.
2. Patient with ulcerative colitis, indeterminate colitis, or ulcerative proctitis.
3. Bowel surgery in past 6 months prior to Screening.
4. Resection of more than 50 cm of the ileum.
5. Current ileostomy or colostomy.
6. Ongoing or active septic complications, is hospitalized or exhibiting signs of toxicity (sepsis), has symptomatic strictures, or impending obstruction or anticipating a need for blood transfusion for gastrointestinal bleeding or in whom surgical intervention may be imminent.
7. Patient with gastrointestinal abscess or perforation.
8. Patient with fistulae having a new onset within 2 months of Screening with moderate to severe local inflammation.
9. Patient with history of colorectal cancer or colorectal dysplasia. Patients with completely resected sporadic adenomas may be enrolled.
10. Patient requiring parenteral or tube feeding.
11. Patient with current evidence of infectious colitis, e.g., Clostridium difficile, Amoebiasis, Giardia lamblia or stools positive for other enteric pathogens, ova or parasites at Screening.
12. Female patient who is pregnant or breastfeeding or wishing to become pregnant during study participation or unwilling to use birth control.
13. Patient with serum creatinine ≥ 2.0 mg/dL; blood urea nitrogen >40 mg/dL; alkaline phosphatase > 250 U/L; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 100 U/L; or total bilirubin >1.5 mg/dL.
14. Patient with hepatitis B virus, hepatitis C virus, liver cirrhosis or portal hypertension, or is known to be human immunodeficiency virus (HIV) positive.
15. Patient with primary sclerosing cholangitis.
16. Patient with malignancy within the past 5 years, with the exception of completely excised squamous or basal cell skin cancers, and cervical carcinoma in situ.
17. Patient received cyclosporine, an anti-TNFα or other immunomodulatory agents other than azathioprine/6-mercaptopurine within 12 weeks prior to Screening.
18. Patient is a primary non-responder an anti-TNFα.
19. Patient is refractory to azathioprine/6-mercaptopurine.
20. Patient received methotrexate within 6 weeks prior to Screening.
21. Patient received metronidazole within 2 weeks prior to Screening.
22. Patient received non-steroidal anti-inflammatory drugs (NSAIDS) within 2 weeks before Baseline visit for more than 3 consecutive days, except acetylsalicylic acid ≤ 350 mg/d which is allowed.
23. Patient 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.
24. Patient with history of drug or alcohol abuse within 6 months prior to Screening.
25. Patient with evidence of poor compliance with medical advice and instruction including diet or medication.
26. Patient is unable or unwilling to swallow study medication suspension.
27. Patient with a significant medical condition which puts the patient at risk for study participation and/or for any reason is considered by the Investigator to be an unsuitable patient to receive CNDO-201 TSO or is potentially put at risk by study procedures.
28. Patient who has participated in another clinical trial within 30 days of Screening for this trial and/or any experimental treatment for this population.