Interim Results from Neovacs SA' Phase II Clinical Trial in Crohn's Disease
Published: Jun 05, 2012
The interim analysis of the cohort of the first 60 patients did not show any statistically significant difference in terms of clinical remission between the Kinoid-treated group and the placebo group. The interim analysis did however demonstrate 3 important points that support further clinical development:
• A statistically significant correlation between clinical remission and the level of antibodies induced by the Kinoid, which confirms the biological activity of the Kinoid. Specifically, in the Kinoid group, the patients achieving remission are those with the highest level of anti-TNF antibodies induced by the Kinoid.
• A major factor explaining non-response to the Kinoid is the ongoing presence of monoclonal antibodies at the time of entry into the study.
• The excellent safety profile of the TNF-Kinoid, consistent with the two previous studies.
All these findings are subject to confirmation in the final phase of the study, results from which will be published in the fourth quarter of 2012.
Neovacs' TNF-K 005 Phase II clinical trial is a double-blind, placebo controlled study conducted in 60 patients with moderate to severe Crohn's Disease (a disease activity by CDAI of between 220 and 450) active on entry and having failed at least one anti-TNF therapy. Patients were enrolled in 7 European countries.
The presence of residual monoclonal antibody levels in a high proportion of patients was unexpected, given a "wash-out" period of several weeks. The residual antibody seems to have had a negative effect on the immune response and thus the clinical effect of the Kinoid, and so may have had a strong influence on the results of the trial. Neovacs has therefore decided:
1. Not to recruit the second cohort into the study, but rather to wait for the additional data that will be generated by the patients already enrolled : per the study protocol, patients who received three doses of the Kinoid have now received a fourth maintenance dose, while patients in the placebo arm have received three doses of the Kinoid The results of the second phase will be available in Q4 2012.
2. To design a new study which will exclude patients with residual anti-TNF monoclonal antibody levels.
"The relationship between clinical remission and anti-TNF antibody titer induced by the Kinoid has been confirmed. The negative impact of residual anti-TNF antibodies on Kinoid immunization is an interesting scientific result, which will assist in the design of future studies. Moreover, taking into account the results seen in January in the study of the TNF-Kinoid in rheumatoid arthritis using the 360 mcg dose, we think we could improve both the response rate and the level of antibodies induced if we used this dose rather than the 180 mcg dose used in this study." commented Guy Charles Fanneau de La Horie, Neovacs' CEO
"Today, thanks to the 3 studies that we have conducted with the TNF-Kinoid, we know that:
1. The TNF-K is safe and well tolerated
2. The TNF-K is immunogenic and 360mcg is the more immunogenic dose
3. A clear relationship exists between TNF antibody titer and clinical remission
4. There is a negative impact of residual anti-TNF antibodies on Kinoid immunization, a factor that will be taken into account in the design of future studies.
The data we expect by the end of the year will be very important to confirm these findings. "We remain very confident in our Kinoid technology platform and the potential for active immunotherapy to become the next generation of treatments for chronic autoimmune diseases."