Safety and Immunogenicity of a TNFa Kinoid in Patients With Crohn's Disease

A Phase I/II, Open-label, Escalating Dose, "Optimal Two-stage", Study of TNFα-Kinoid (TNF- K) Immunization in Crohn's Disease Patients

Evaluation of the safety and the immune response induced by active immunization through a TNFa kinoid in patients with Crohn's disease.

Inclusion Criteria:

• Subjects must have Active Crohn's Disease, as defined by a Crohn's Disease Activity Index (CDAI) score of >220 but ≤400, with active Crohn's disease of ileum and/or colon (Other areas may be involved if ileum and/or colon are also involved)based upon either endoscopic, histologic and/or radiographic evidence
• Patients with active disease despite treatment with 5-ASAs or sulfasalazine, corticosteroids (prednisone, budesonide, other), AZA or 6-MP or cyclosporine or MTX or Tacrolimus, ; OR intolerant of 5-ASAs or sulfasalazine; or intolerant of antibiotics; or intolerant of corticosteroids (prednisone, budesonide, other); or intolerant of AZA or 6-MP or cyclosporine or MTX or Tacrolimus
• Patients might have previously responded to any prior anti-TNF agents and then lost response OR might be intolerant of any prior anti-TNF agents
• Positive skin reaction to challenge with Candida antigens
• Written informed consent

Exclusion Criteria:

• Prior history of tuberculosis or positive chest X ray or positive purified protein derivative skin test or positive interferon gamma TB assay
• Signs or symptoms of clinically significant stricture of bowel.
• Total parenteral nutrition or elemental diet required for treatment of disease or support of short bowel syndrome
• Presence of an enteric stoma
• Imminent or urgent surgery required for infection, abscess, bleeding or any other cause relating to their Crohn's Disease or other condition
• History of malignancy. However, subjects with basal call carcinomas or less than 3 squamous cell carcinomas are allowed
• History of asthma or serious allergic condition (including history of seafood allergy)
• Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., pneumonia, septicemia) within the 3 months prior to the first dose of study drug
• History of opportunistic infection excluding oral candidiasis on steroids
• Enteric infection as evidenced by positive stool C&S, O&P and C. difficile obtained during screening
• Any significant or decompensated cardiac, neurologic, liver, pulmonary or renal disease
• History of lymphoproliferative disorders
• Clinically significant abnormal hematology values, as determined by the investigator, for hematocrit, hemoglobin, white blood cell count or platelets
• Clinically significant abnormal blood chemistry values as determined by the investigator
• Current significant drug or alcohol abuse as determined by the investigator
• Positive for hepatitis C antibody or positive for hepatitis B surface antigen (HbsAg) or HIV infection
• Surgery within the previous 3 months (other than minor cosmetic surgery or minor dental procedures)
• Participation in a clinical study (including previous participation in this study) within the previous 4 months
• Had a primary non-response to any prior anti-TNF agents as defined by the investigator OR received any prior anti-TNF agents within the past 8 weeks prior to study entry
• Pregnancy and lactation