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

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

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

Conditions
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Crohn's Disease

Intervention / Treatment
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* Biological: TNFa Kinoid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TNFa Kinoid dose 1<br> | Biological: TNFa Kinoid<br>* TNFa kinoid at days 0, 7, 28<br>|
| Experimental: TNFa Kinoid dose 2<br> | Biological: TNFa Kinoid<br>* TNFa kinoid at days 0, 7, 28<br>|
| Experimental: TNFa Kinoid dose 3<br> | Biological: TNFa Kinoid<br>* TNFa kinoid at days 0, 7, 28<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events |  | Whole study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody response |  | Day 38 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anti-TNFa, immunization, kinoid, crohn's disease