OP0079 A RANDOMIZED, DOUBLE-BLIND, PLACEBO-AND-TOCILIZUMAB CONTROLLED PHASE II TRIAL OF VDJ-001, A HIGH-AFFINITY IL-6R ANTAGONIST ANTIBODY, FOR THE TREATMENT OF PATIENTS WITH RHEUMATOID ARTHRITIS

Objectives:

VDJ-001 is a novel humanized IgG1 monoclonal antibody designed to enhance the therapeutic index of Tocilizumab. Based on a random B-cell hyper-mutation and display technology, which mimics the native mechanism of antibody affinity maturation in vivo, VDJ-001 has been selected for its higher-affinity and more potent biological activities in comparison with Tocilizumab. The present study is to assess the comparative efficacy and safety of VDJ-001 in patients with rheumatoid arthritis following its pre-clinical and early clinical evaluation.

Methods:

In this double-blind, placebo and positive drug-controlled phase II study, 180 adult patients with moderate-to-severe active rheumatoid arthritis who had inadequate response to methotrexate (MTX) were randomly assigned to 4-treatment arms in 1:1:1:1 ratio, i.e., 4 mg/kg and 6 mg/kg of VDJ-001, 8 mg/kg of Tocilizumab, or placebo, i.v. q4w. All patients also received standard dose of methotrexate treatment. The primary endpoint was to compare the proportion of patients achieving ACR20 response at week 12; while secondary endpoint included the comparative analysis of patients achieving ACR50 and ACR70 responses at week 12 (NCT05957107, CTR20220613).

Results:

Both doses of VDJ-001 are safe and well-tolerated in 90 patients, most of them with low grade I-II of adverse reaction. Their safety profile is similar to Tocilizumab arm, which could be managed very well even during Covid-19 restriction period. In comparison with placebo arm (<60% responders), patients treated with both doses of VDJ-001 and Tocilizumab all reached a similar significant efficacy (p<0.05) on ACR20 response (>80% responders). Moreover, a clear trend on the potency ranking has been observed on ACR50/70 responders, i.e. VDJ-001 6mg/kg (64.3%) > Tocilizumab 8mg/kg (55.8%) > VDJ-001 4mg/kg (42.9%) > placebo (8.1%) for ACR50 responders; while VDJ-001 6mg/kg (33.3%) > Tocilizumab 8mg/kg (25.6%) > VDJ-001 4mg/kg (16.7%) > placebo (0%) for ACR70 response rates. There is a good correlation between pharmacokinetics and pharmacodynamics (sIL-6R) of VDJ-001 and Tocilizumab in a dose-dependent manner; while the disease biomarker change (ESR) is highly correlated with their corresponding efficacy.

Conclusion:

VDJ-001 is safe and effective in patients with rheumatoid arthritis. Its higher affinity and higher biological activity seem to be associated with the tendency of higher efficacy. The highly competitive rate (33.3%) on ACR70 response makes VDJ-001 6 mg/kg one of the best treatment options for RA patients.

REFERENCES:

NIL.

Acknowledgements:

Beijing VDJBio Co., Ltd.

Disclosure of Interests:

None declared.