Clinical Efficacy of TNFa Kinoid in Crohn's Disease Patients

Study Overview
=================
Brief Summary
-----------------
The safety and immunogenicity of the TNFα-Kinoid (TNF-K) have been evaluated in a phase I-II clinical study conducted in subjects with Crohn's Disease (CD). Preliminary results of clinical efficacy are promising. The principal aim of the present study is to confirm the clinical efficacy of the TNF-K in subjects with moderate to severe CD. Subjects with secondary resistance or intolerance to anti-TNFα monoclonal antibodies will be enrolled in this trial. In addition, the immune responses and the safety elicited by TNF-K will also be evaluated.

Official Title
-----------------
A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Clinical Efficacy, Safety and Immunogenicity of Neovacs' TNFα-Kinoid in Adult Subjects With Crohn's Disease

Conditions
-----------------
Crohn's Disease

Intervention / Treatment
-----------------
* Biological: TNF Kinoid
* Biological: WFI


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female aged 18 to 65 years, inclusive. Have had a diagnosis of Crohn's disease for at least 6 months. Moderate to severe active Crohn's disease defined as a Crohn's Disease Activity Index (CDAI) score ≥ 220 and ≤ 450, and presence of colonic mucosal ulcerations in at least 2 segments, or ulcerations on ≥ 10% of the mucosal surface if only one segment is involved. Have developed secondary resistance to anti-TNFα therapy. Exclusion Criteria: Primary non-response to a previously received treatment directed against TNFα Or Intolerance related to the primary pharmacological effect of anti-TNFα such as for instance, but not limited to, severe or opportunistic infections and demyelinating or autoimmune diseases. History of severe systemic bacterial, fungal, viral, or parasitic infections within the 3 months prior to screening; or the occurrence of any acute infection within 2 weeks of the first administration of study drug. Treatment with immunosuppressive or immunomodulatory drugs

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TNF Kinoid<br> | Biological: TNF Kinoid<br>* TNF Kinoid<br>|
| Placebo Comparator: Placebo<br> | Biological: WFI<br>* WFI<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical remission, defined as a CDAI score ≤ 150 points at week 8. |  | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical responses, defined as a decrease of at least 70 points (CDAI-70) and at least 100 points (CDAI-100) in the CDAI score at week 8 vs baseline |  | week 8 | 
| Endoscopic response, defined as a reduction of at least 50% in the Crohn's Disease Endoscopic Index of Severity (CDEIS) score or in the Simple Endoscopic Score for Crohn's Disease (SES-CD) at week 12 vs baseline |  | week 12 | 
| Biological response as defined by a decrease or normalization of calprotectin levels in stools |  | Week 12 | 
| Safety assessments will be conducted throughout the study and will include physical examinations, vital signs, 12-lead electrocardiograms (ECGs), clinical laboratory evaluations, and the recording of adverse events (AEs). |  | Week 28 | 
| Immunogenicity: o Anti-TNFα antibodies by Enzyme-Linked Immunosorbent Assay (ELISA) o Anti-TNFα neutralizing antibody activity o Anti-KLH antibodies by ELISA |  | week 12 |