Clinical Efficacy of TNF-Kinoid in Patients With Rheumatoid Arthritis

Study Overview
=================
Brief Summary
-----------------
The safety and immunogenicity of the TNF-Kinoid (TNF-K) have been evaluated in a phase II clinical study conducted in subjects with Rheumatoid arthritis. 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 Rheumatoid arthritis in whom treatment with methotrexate is not working anymore. Subjects who have never been treated with 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 of Neovacs' TNF-Kinoid in Adult Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Biological: TNF-Kinoid
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Has had a diagnosis of RA according to the revised ACR criteria (Aletaha et al. 2010) for at least 6 months. Has been treated with and tolerated MTX for at least 3 months prior to the first administration of study product, - Has at least four swollen joints/66 and/or four tender joints/68, Has CRP ≥ 10 mg/L at screening. Is positive for rheumatoid factor (RF) or anti-cyclic citrullinated peptides (CCP) antibodies at screening. Exclusion Criteria: Has inflammatory rheumatic disease other than RA Has been treated with non-biological DMARDs/systemic immunosuppressives Has been treated with leflunomide within 12 weeks prior to first administration of study product. Has received intra-articular, intramuscular (IM), or intravenous (IV) corticosteroids Has received infliximab, etanercept, adalimumab, certolizumab, golimumab; another TNFα antagonist; or rituximab prior to the study. Has been treated with any other biological DMARDs

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TNF-Kinoid<br>TNF Kinoid + ISA51 | Biological: TNF-Kinoid<br>* IM administration<br>* Other names: ISA 51;|
| Placebo Comparator: Placebo<br>Placebo + ISA51 | Other: Placebo<br>* IM administration<br>* Other names: ISA 51;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in DAS28-CRP between Month 6 and baseline. |  | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical responses defined as ACR20, ACR50, ACR70, SDAI, EULAR responses, changes in Tender and Swollen joint counts, DAS-28 and HAD-QI versus baseline |  | Several timepoints during 24 weeks study period | 
| Immunogenicity: Anti-TNFα antibodies, Anti-TNFα neutralizing antibody activity, Anti-KLH antibodies by ELISA ; cytokines |  | Several timepoints during 24 weeks study period | 
| Safety assessments will be conducted throughout the study and will include physical examinations, vital signs, clinical laboratory evaluations, and the recording of adverse events (AEs) |  | Several timepoints during 24 weeks study period |