Background/Purpose:

The 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 consisting of the targeting antibody F8 (specific to EDA) fused to the anti-inflammatory payload interleukin-10. Dekavil is currently in phase 2 clinical development for the treatment of rheumatoid arthritis (RA).

Methods:

Patients diagnosed with RA according to ACR/EULAR classification criteria, who have active disease despite MTX therapy and who failed anti-TNF treatment are the target population.

In a recently completed phase 1b dose escalation study with the aim to explore safety, tolerability and the maximum tolerated dose (MTD), cohorts of 3-6 patients were treated with escalating doses of Dekavil (6-600 μg/kg + MTX). Patients received 4 weekly s.c. injections of Dekavil in combination with a fixed dose of MTX (10-15 mg). Patients willing to continue the treatment had the opportunity to receive 4 additional weekly injections of Dekavil.

The ongoing multicenter, double-blind, placebo-controlled phase 2 trial assesses therapeutic activity by measuring the mean change from baseline of DAS28-CRP. Patients are randomized into two treatment groups (Dekavil 30 or 160 μg/kg plus MTX) and one placebo group (placebo plus MTX). Study participants receive 8 weekly s.c. injections of Dekavil in combination with a fixed dose of MTX (10-15 mg).

Both studies further investigate the possible formation of anti-fusion protein antibodies as well as F8IL10 signature.

Results:

In the phase 1 study, Dekavil was shown to be 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 DLTs, no SAEs and no SUSARs have been reported. One study subject in cohort 9 (450 μg/kg) experienced a DLT (G2 purpura), which was accompanied by a SAE (G2 dyspnea, not drug related). The patient fully recovered within one week after having received corticosteroid treatment. The most frequently observed adverse event was mild injection site reaction and occurred in 60% of the patients. Furthermore, two cases of drug related anemia (G3 and G2; 160 μg/kg and 450 μg/kg, respectively) were reported in this study. All adverse reactions resolved completely. At the first efficacy assessment after 4 cycles of treatment, 36.4% of patients (12/33) revealed ACR responses. The fraction of responding patients increased to 45.8% (11/24) after 8 cycles of treatment. Two patients benefited from a long lasting ACR70 responses for more than 12 months after the last drug administration.

As of May 2017, 23 out of 87 patients have been enrolled in the phase 2 clinical study. Neither SAE nor SUSARs nor treatment-related deaths were recorded so far. An interim analysis performed after 45 patients will allow for a more thorough understanding of the product.

Conclusion:

The currently available data suggest that the biologic agent Dekavil is a safe and well tolerated novel therapeutic approach for the treatment of RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/update-on-the-clinical-phase-1-and-phase-2-trials-investigating-the-fully-human-immunocytokine-dekavil-f8il10-in-patients-with-rheumatoid-arthritis/