Clinical Trials

Date: 2012-11-12

Type of information: Results

phase: 2a

Announcement:

results

Company: Neovacs (France)

Product: TNF-Kinoid®

Action mechanism:

kinoid/immunotherapy productA Kinoid is obtained by chemically linking the cytokine of interest to a foreign carrier protein, KLH ( Keyhole Limpet Hemocyanin), and then treating the resultant compound to inactivate the cytokine. These active immunotherapies have been designed to induce an antibody response by the patient’s immune system that targets a particular over-expressed cytokine responsible for the pathogenesis and development of a given disease. The Kinoid technology can be applied in principle to any cytokine target. Three targets (Tumor Necrosis Factor (TNF), Interferon alpha (IFN alpha) and Vascular Endothelial Growth Factor (VEGF) are considered as playing a key role in the pathogenesis of certain diseases.

Disease: rheumatoid arthritis

Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases

Country: France, Argentina, Belgium, Bulgaria, Chile, Croatia, Romania

Trial details:

Latest news:

* On November 12, 2012, Neovacs, a biotech company focused on the development of active immunotherapies to treat autoimmune and inflammatory diseases, presented Month 6 follow–up results of its TNF–Kinoid Phase II study in Rheumatoid Arthritis (RA). These findings confirm and strengthen previously released results. These new data were presented in a poster during the Annual Meeting of the American College of Rheumatology on November 11, 2012 in Washington,DC.
The new data at month 6, compared to previously released Month 3 data, show a further improvement
in clinical symptoms linked to RA for patients in whom the Kinoid induced antibody (Abs) to TNF, compared to those without such antibody:
1. At month 6, for patients in whom the Kinoid induced anti-TNF Abs, the average DAS281 score decline is larger than in patients not developing such Abs (–1.38 vs. –0.76 respectively). This confirms the pattern previously observed at month 3 (–1.03 vs. –0.38 respectively).
2. 89% of RA patients in whom the Kinoid induced antibody (Abs) to TNF at month 6, showed a moderate to good EULAR response, compared to 53% in patients without Abs. This positive distinction was already observed at month 3, although not as strongly.
3. At month 6, the level of serum C reactive protein (CRP, a marker of inflammation) shows a 27% mean decline in patients who developed anti–TNF Abs compared to a 13% increase in patients not having such Abs. At month 3, an 11% mean decline had already been observed, compared to a 2% decline in patients without antibody.
These follow up study results further confirm the excellent safety profile of the TNF–Kinoid, as no serious adverse event has been reported. Similarly, the new data confirms the most effective administration course (3 injections) and dose (360 microg). Summary of Phase IIa study of TNF–Kinoid in RA has been presented in January 2012 (See below).
* On January 5, 2012, Neovacs ® has announced final and positive results of its clinical study TNF-K-003 with TNF Kinoid ® in rheumatoid arthritis. The efficacy and safety of TNF Kinoid ® were evaluated in patients with rheumatoid arthritis who became resistant to anti-TNF biologic therapies with monoclonal anti-TNF. These final results confirm the excellent safety profile of TNF-Kinoid®, its effectiveness in inducing anti-TNF and the trend towards clinical improvement of symptoms related to the disease. This work also enabled the identification of two doses and an administration schedule that are immunogenic.
Final results concern 40 patients: 
- in the intermediate results, 6 patients received a dose of 90 mcg, 12 patients received a dose of 180 mcg and 6 patients received placebo.
- 12 of the remaining 16 patients have received the 360mcg dose and 4 the placebo.
Two immunization schedules were tested: two injections 4 weeks apart or three injections given on days 0, 7 and 28. It is important to note that patients included in this study were no longer responding to at least one anti-TNF biological treatment. Some of them were in their second or their third anti-TNF treatment after failure of previous treatments.
The main objective of the study was to identify a dose and an effective immunization schedule. Three months after immunization, only 50% of patients treated with 90 mcg dose developed antibodies to TNF. This dose proved to be poorly immunogenic.
At the 180 mcg dose, 75% of patients developed antibodies and for the 360mcg dose, the corresponding figure was 91%, suggesting a dose-effect.
At doses of 180 and 360 mcg, the success rate is 100% with the immunization schedule with 3 injections when it was only 67% in the figure to 2 injections. Therefore, the analysis of clinical efficacy was made according to the criterion presence or absence of anti-TNF.
These results also confirm the excellent safety profile of TNF-Kinoid ®, no patient left the study for side effects and no major side effects associated with the Kinoid were reported.
The study reveals an improvement in symptoms associated with rheumatoid arthritis in patients who developed anti-TNF. This observation is objectified by:
1- clinical response as moderate to good EULAR criteria (decrease of at least 0.6 point of DAS28 and DAS28 final of less than 5.1). In the group of 21 patients of the 24 who developed antibodies to TNF measured during the first 84 days, 48% have a moderate to good clinical response, a decrease of 0.6 points minimum - against only 31% in the group of 16 patients who did not develop anti-TNF.
2- the fall in the average DAS28 . The decline in average score is 0.8 point DAS measured in patients who developed antibodies to TNF, whereas in patients without anti-TNF, this decline is only 0.5 point.
3- decline in CRP (C reactive protein), a marker of inflammation. An average decrease of 14% of CRP was measured in patients who developed antibodies to TNF, whereas in patients without anti-TNF, the average CRP increase of 5%.
* On October 26, 2011, Neovacs® has announced promising results achieved in the first 24 rheumatoid arthritis patients included in the Phase IIa study conducted with TNFKinoid®. These initial results confirm the good safety profile of the TNF-Kinoid®, its ability to induce an immune response in patients and provide evidence of promising clinical efficacy. These first clinical data from the TNF-K-003 study, with an ACR20 response in over 50% of patients raising an anti-TNF immune response and a sharp drop in CRP are very encouraging and promising. The results announced here relate to the first 24 patients, who received the first two dose levels of the TNF-Kinoid®: 6 patients received the 90mcg dose, 12 the 180mcg dose and 6 the placebo. The results of the remaining 16 patients, of whom 12 have received the 360mcg dose and 4 the placebo will be known in December. No patient withdrew from the study because of an adverse event, and no serious adverse event related to the Kinoid was recorded. The immune response data measured at two months is also very positive: at the 90mcg dose, 50% of patients developed antibodies to TNF, whereas for the 180mcg dose the corresponding figure was 80%, which suggests a dose-response effect.
Initial clinical efficacy data has been collected, based on a study design that tracks the development of RA symptoms, in particular looking at ACR20*, a 20% decline in a composite disease index established by the American College of Rheumatology. A second measure is the change over time in C-reactive protein (CRP), a marker of inflammation. In the 11 patients who developed measurable antibodies to TNF up to day 84, 55% saw a decline of at least 20% in their ACR score (ACR20), versus only 20% in the group of 10 patients without antibody to TNF. On average, the level of CRP fell by 42% in patients who developed antibodies to TNF, versus an increase of 12% in patients without anti-TNF antibodies. The full analysis of all 40 patients in the study is planned for the end of the year, which will allow Neovacs to define more fully the impact of the TNF-Kinoid® on RA in patients who have developed resistance to biologic TNF inhibitors and thus need an effective therapeutic alternative.
* On August 3, 2011, Neovacs has announced that its TNF-K-003 clinical study has recruited all patients called for by the study protocol and consistent with the Company’s development plan. Initial results relating to the first two dose (90 and 180 mcg) cohorts should be released during fall 2011 and the final results by end 2011. This Phase IIa study is being conducted in partnership with bmd, a French diagnostics company, and partly financed by Oséo, the French State innovation agency, up to a maximum of €7.5 million of which €6.4 million is intended for Neovacs. The aim of the Tracker project is to develop a holistic therapeutic strategy for patients with rheumatoid arthritis who have developed a secondary resistance to TNF-inhibitors.

Is general: Yes