Clinical Trials

Date: 2015-09-09

Type of information: Presentation of results at a congress

phase: 1-2

Announcement: presentation of results at the 11th International Congress on Systemic Lupus Erythematosus (SLE), which took place from 2 to 6 September 2015 in Vienna, Austria.

Company: Neovacs (France)

Product: IFN alpha-Kinoid® (IFN-K)

Action mechanism: kinoid/immunotherapy product. A 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 (IFNalpha) and Vascular Endothelial Growth Factor (VEGF) are considered as playing a key role in the pathogenesis of certain diseases.

Disease: systemic lupus erythematosus

Therapeutic area: Autoimmune diseases

Country:

Trial details: The IFN-K-001 Phase I/II study is a double-blind, placebo-controlled, dose-escalation design testing four different IFN alpha-Kinoid dose levels. All patients recruited have mild to moderate lupus, defined as a SLEDAI1 score of between 4 and 10. The main endpoints of the trial are the safety and tolerance of the IFN alpha-Kinoid, its capacity to induce an antibody response to IFN alpha, the evolution of clinical disease scores (such as SLEDAI) and biomarkers for disease activity, including the interferon signature which measures changes in the activity of genes that are overexpressed in lupus.

Latest news:

• • On September 9, 2015, Neovacs, a leader in active immunotherapies for the treatment of autoimmune diseases, announced that it presented extended follow-up data from the Phase I/IIa clinical trial of IFN alpha-Kinoid during Lupus 2015, the 11th International Congress on Systemic Lupus Erythematosus (SLE), which took place from 2 to 6 September 2015 in Vienna, Austria. This new data, collected as part of the Phase I/IIa extended follow-up study of six IFNalpha-Kinoid-treated patients, demonstrates that anti-IFNalpha neutralizing antibodies generated by IFNalpha-Kinoid continue to be present four years after the first immunization, and maintain the normalization of the IFNalpha signature. This confirms previously reported results. The study also highlights the association between anti-IFNalpha neutralizing antibodies and the decreased expression of induced genes associated with B cell activation. B-cell activation, like the IFNalpha-signature, has been linked to the pathogenesis of SLE lupus.
• Follow up data from the Phase I/IIa clinical trial was presented in the poster "IFNalpha-kinoid (IFN-K) induces neutralizing anti-IFNalpha antibodies that decrease the expression of IFN-induced and B cell activation associated transcripts : Analysis of extended follow-up data from the IFN-K Phase I/IIa study"1 on Friday, September 4, 2015 in Vienna. Data was collected on six IFNalpha-Kinoid-treated patients included in the Phase I/IIa clinical trial of IFNalpha-Kinoid in SLE or lupus. Five of the six patients presented a positive IFN-signature at baseline. The same level of normalization of the IFN-signature as previously reported was observed in two out of five patients who developed neutralizing antibodies. Correlation in the increase of C3 serum level and neutralizing anti-IFNalpha antibodies also persisted in the same two patients, confirming previously reported results.
• • On July 26, 2011, Neovacs has published the data of the last cohort of patients in a phase I/II study with IFN alpha-Kinoid in Lupus patients. These patients had received 240 mcg of IFN-K, the highest dose of IFN-K tested. These preliminary confirm those which had been presented at the 8th European Lupus Meeting in Porto on April, the 8th 2011 (See below). These new results confirm the previous set of data generated at lower doses of IFN-K:
• - The dose of 240 mcg of IFN-K was well tolerated. Two serious adverse events (lupus flares) were recorded and their causes were quickly identified: One of them occurred in the placebo group and the other one in a patient who had spontaneously interrupted her steroid treatment after the first injection of kinoid.
• - IFN-K, at the dose of 240 mcg, induced the production of antibodies to interferon alpha in all patients. In some patients, these antibodies could be measured as soon as on day 28, i.e. after the first 2 injections.
• - IFN-K generated a significant downregulation of some overexpressed genes associated with interferon alpha and lupus.
• Another very promising piece of news is that with a longer follow-up it was found out that IFN-K at all doses induced the production of anti-interferon alpha antibodies in all patients, instead of 80% of patients as previously observed. Final results of the Phase I/II with IFN-K in lupus will be published by the end of Q3 2011.The thorough analysis of the data in all 28 patients is on-going. It will be presented by Neovacs in scientific meetings.
• • On April 8, 2011, Neovacs has published the initial results of the phase I/II study with IFNalpha-Kinoid in Lupus patients. These results are presented at the 8th European Lupus Meeting in Porto and highlight the good safety, the immunogenicity and the pharmacodynamic of the IFNalpha-Kinoid. They relate to the first three dose groups (30, 60 or 120 mcg of the Kinoid), comprising in total 20 patients. Results for the highest dose group of 8 patients at 240 mcg (including 2 placebo patients) are currently collected and analyzed. Across all the patients recruited in the first three dose cohorts, there has been no significant adverse event associated with the Kinoid, no unusual infection, and no patient has dropped out. This demonstrates the favourable safety profile of the product at these dose levels. The IFNalpha-Kinoid is highly immunogenic: Antibodies to IFNalpha have been induced in 80% (12 of 15) patients treated with the Kinoid. This very good score highlights the clear induction of an immune response with the IFNalpha-Kinoid. As expected, no immune response to IFNalpha was detected in the 5 placebo patients. The use of gene signatures has become an important tool to identify the genes implicated in diseases and to measure the impact of therapies. The interferon gene signature analysis has been done in 18 of the 20 patients included in this interim analysis. Of these 18 patients, 11 had a positive interferon alpha signature on study entry: 8 were treated with the Kinoid and 3 received the placebo. The Kinoid-treated group experienced a sharp reduction in interferon signature, demonstrating a significant down-regulation of genes associated with IFN. The interferon gene signature will be included as one of the endpoints to be studied in later stages of development of the product. The median SLEDAI score declined in all the groups.
• • On February 21, 2011, Neovacs announced that its IFN-K-001 clinical study has recruited all 28 patients called for by the study protocol. Initial results will be the subject of a poster presentation at the 8th European Lupus Meeting on April 8th in Porto.

Is general: Yes