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.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Biological: TNFa Kinoid

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• South Africa
  • Bloemfontein, South Africa
    • Farmovs Parexel
  • George, South Africa
    • PAREXEL George
  • Cape
    • Cape Town, Cape, South Africa, 7550
      • Durbanville Medi-Clinic
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa
      • PAREXEL Port Elizabeth
• Switzerland
  • Lausanne, Switzerland
    • Centre Hospitalier Universitaire Vaudois
  • Zurich, Switzerland
    • UniversitätsSpital Zürich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TNFa Kinoid dose 1	Biological: TNFa Kinoid; TNFa kinoid at days 0, 7, 28
Experimental: TNFa Kinoid dose 2	Biological: TNFa Kinoid; TNFa kinoid at days 0, 7, 28
Experimental: TNFa Kinoid dose 3	Biological: TNFa Kinoid; TNFa kinoid at days 0, 7, 28

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Antibody response	Day 38

Collaborators and Investigators

• Sponsor: Neovacs
• Investigators: Study Director: Pierre Vandepapeliere, MD, PhD, Neovacs

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: December 12, 2008
• First Submitted That Met QC Criteria: December 12, 2008
• First Posted (Estimate): December 15, 2008

Study Record Updates

• Last Update Posted (Estimate): June 8, 2011
• Last Update Submitted That Met QC Criteria: June 7, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: immunization; crohn's disease; anti-TNFa; kinoid
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: TNF-K-001