aCL, when present at medium-high titer, are as important as abeta2GPI, as a risk factor for thrombosis. Medium-high titer aCL, but not abeta2GPI, are associated with other clinical features of the antiphospholipid syndrome.

BackgroundThe targeted pharmacodelivery of cytokines by means of antibody-fusion proteins aims at selective accumulation of the active compound at the site of disease while sparing healthy tissues. Dekavil (F8IL10) is a fully human fusion protein composed of the vascular targeting antibody F8 fused to the cytokine interleukin-10. A phase 1 dose escalation study in patients with rheumatoid arthritis (RA) has recently been completed. Dekavil is currently under investigation in a phase 2 clinical study for the treatment of RA.ObjectivesThe phase 1 study investigated safety, tolerability and the maximum tolerated dose of Dekavil when administered in combination with methotrexate (MTX). The currently ongoing phase 2 (in patients with active RA despite MTX therapy who had failed anti-TNF treatment) measures the mean change from baseline in DAS28-CRP between F8IL10 and placebo arms as primary endpoint.MethodsThe target population of both RA studies comprises patients with active RA despite MTX therapy who had failed anti-TNF treatment. Dekavil is administered once weekly for 8 consecutive weeks by s.c. injection in combination with a fixed dose of MTX (10–25 mg). The recently completed phase 1 study investigated escalating doses of Dekavil (6–600 µg/kg +MTX). The ongoing randomised multicenter, double-blind, placebo-controlled phase 2 trial assesses therapeutic activity in two treatment groups (Dekavil 30 or 160 µg/kg plus MTX) and one placebo group (placebo plus MTX).ResultsDekavil was well tolerated up to the highest investigated dose (600 µg/kg) and an MTD was not reached. In 34 out of 35 patients treated in the phase 1 study no SAEs and no SUSARs were reported. One subject (cohort 9, 450 µg/kg) experienced a DLT (G2 purpura), which was accompanied by an SAE (G2 dyspnea, not drug related). The patient fully recovered within one week following corticosteroid administration. The most frequently observed adverse event was mild (G1) injection site reaction and occurred in 60% of the patients. Furthermore, two cases of drug related anaemia (G3 and G2; 160 µg/kg and 450 µg/kg, respectively) were reported in this study. All adverse reactions resolved completely. After 4 cycles of treatment, 36.4% of patients (12/33) exhibited ACR responses. The fraction of responses increased to 45.8% (11/24) after 8 cycles. Two patients achievedan ACR70 for more than 12 months after the last drug administration.As of January 2018, 25 patients have been treated in the phase 2 clinical study and neither SUSARs nor treatment-related deaths were recorded. Immunogenicity assessment is completed for the first 20 study subjects did not reveal an antibody response specific to F8IL10. An interim read-out after 45 patients will provide a more thorough understanding of the therapeutic activity of F8IL10.Abstract FRI0118 – Figure 1ACR responses after 4 and after 8 weeks of Dekavil treatment in the phase 1 study population including all dose levels (6 – 600μg/kg)ConclusionsThe data obtained in the population studied to date suggest that Dekavil may be a...

BackgroundThe antibody-based targeted pharmacodelivery of cytokines by means of immunocytokines has the potential to enhance therapeutic activity at the site of disease while sparing healthy tissues. Dekavil (F8IL10) is a fully human immunocytokine composed of the vascular targeting antibody F8 (specific to EDA) fused to the cytokine interleukin-10. Dekavil is currently in phase II clinical development for the treatment of rheumatoid arthritis (RA).ObjectivesIn the phase Ib dose escalation study, the primary objective was to explore safety, tolerability and the maximum tolerated dose of Dekavil when administered in combination with methotrexate (MTX). The aim of the currently ongoing phase II study is to assess therapeutic activity of Dekavil plus MTX over MTX alone by measuring the mean change from baseline of DAS28-CRP. Immunogenicity of F8IL10 and its PK and PD profile will also be explored.MethodsPatients with active RA despite MTX therapy and who failed anti-TNF treatment are the target population of both studies. In the phase Ib trial, cohorts of 3–6 patients were treated with escalating doses of Dekavil (6, 15, 30, 60, 110, 160, 210, 300, 450 and 600 μg/kg) in combination with a fixed dose of MTX (10–15 mg). In the multicenter, double-blind, placebo-controlled phase 2 study, patients are randomized into two treatment groups (Dekavil 30 or 160 μg/kg plus MTX) and one placebo group (placebo plus MTX). Dekavil is administered once weekly by s.c. injection for a maximum of 8 weeks in both studies.ResultsDekavil has been shown to be well tolerated up to the highest investigated dose (600 μg/kg) and an MTD was not reached. In 33 out of 34 patients treated in the phase 1 study, no DLTs, no SAEs and no SUSARs have been reported. One patient in cohort 9 (450 μg/kg) experienced a DLT (G2 purpura) and a SAE (G2 dyspnea, not drug related). The patient received corticosteroids and fully recovered within one week. Mild injection site reactions were the most frequently observed adverse events and occurred in 62% of the patients. Furthermore, two cases of drug related anemia (G2 and G3) were reported in this study. All adverse reactions resolved completely. At the first efficacy assessment after 4 cycles of treatment, 48% of evaluable patients (16/33) revealed ACR and/or EULAR responses. The fraction of responding patients increased to 57.7% (15/26) after 8 cycles of treatment. Two patients benefited from ACR70 responses for more than 12 months after the last drug administration. As of January 2017, 22 out of 87 patients have been treated in the phase 2 clinical study and neither SUSAR nor treatment-related deaths were recorded.ConclusionsThe currently available data suggest that Dekavil is a safe and promising novel therapeutic for the treatments of RA.Disclosure of InterestM. Galeazzi: None declared, G. Sebastiani: None declared, R. Voll: None declared, J. Wollenhaupt: None declared, O. Viapiana: None declared, J. Dudler: None declared, E. Selvi: None declared, C. Baldi: None declared, M. Bardelli: None declared, B. Bann...

aCL, when present at medium-high titer, are as important as abeta2GPI, as a risk factor for thrombosis. Medium-high titer aCL, but not abeta2GPI, are associated with other clinical features of the antiphospholipid syndrome.

BackgroundF8-IL10 (Dekavil) is a fully human immunocytokine, composed of the antibody fragment F8, specific to the extradomain A of fibronectin (EDA-FN), fused to the anti-inflammatory cytokine interleukin-10 (IL-10) [1, 2]. F8-IL10 is currently being investigated as a new therapeutic strategy targeting the inflamed tissues in rheumatoid arthritis (RA).ObjectivesTo determine the safety and tolerability of Dekavil when administered in combination with methotrexate (MTX) to patients suffering from RA who had failed at least one anti-TNFα drug therapy. To give a preliminary evaluation of the efficacy of Dekavil when administered in combination with MTX.MethodsA Phase Ib non-placebo controlled clinical trial is currently ongoing in order to establish the maximum tolerated dose (MTD) of Dekavil when administered in combination with MTX. Cohorts of 3-6 patients are treated with escalating doses of Dekavil (6, 15, 30, 60, 110, 160, 210, 300, 450 and 600 μg/kg) in combination with a fixed dose of MTX. Dekavil is administered by subcutaneous injection once a week for a maximum of 8 weeks.ResultsAs of today, the first eight cohorts of the study have been completed (dose levels from 6 to 300 μg/kg). Twenty-six patients are evaluable for safety. No dose limiting toxicities nor serious adverse events have been recorded. No MTD has yet been reached; the dose level of 450 μg/kg is currently ongoing.Mild injection site reaction has been reported in 54% of patients. Regarding systemic adverse reactions, one case of progressive anemia was reported in one patient treated at 160 μg/kg. All adverse reactions resolved after the end of treatment with minor or no therapeutic interventions. A therapeutic benefit of Dekavil, in terms of ACR response, has been recorded in the treated patients, even in subjects treated with low drug dosages. To date, 25 patients are evaluable for efficacy. Among this population, ACR20, 50 and 70 responses were achieved by 60%, 32% and 16% of patients, respectively. In addition, two patients treated at 30 μg/kg and 60 μg/kg dose levels achieved a long-lasting remission.ConclusionsThe promising safety profile, together with the preliminary efficacy responses in this non-placebo controlled trial led to the start of a Phase II placebo-controlled trial within the same patient population to verify the efficacy of low dosages of Dekavil in combination with MTX. The currently available data suggest the targeted delivery of IL-10 to the sites of inflammation is a promising therapeutic approach for RA.ReferencesK. Schwager et al. (2009) Arthritis Res. Ther., 11, R142F. Doll et al (2013) Arthritis Res. Ther., 15, R138Disclosure of InterestM. Galeazzi: None declared, G. Sebastiani: None declared, L. Bazzichi: None declared, E. Garcia Gonzalez Consultant for: Philogen, N. Ravenni Employee of: Philogen, L. Giovannoni Employee of: Philogen, J. Wilton Consultant for: Philogen, E. Selvi: None declared, M. Bardelli: None declared, C. Baldi: None declared, A. Iuliano: None declared, G. Minisola: None declared, R. Caporali: Non...