Novel cell trafficking inhibitor E6011 is moderately effective in people with moderate to severe rheumatoid arthritis (RA) who demonstrated an inadequate response to methotrexate treatment. This is according to research results published in Arthritis & Rheumatology.
In a phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study, researchers set out to compare the safety and efficacy of E6011, a humanized immunoglobulin-G2 (IgG2) monoclonal antibody with human fractalkine. (ClinicalTrials.gov identifier: NCT02960438)
Participants were randomly assigned in a 2:1:2:2 ratio to receive either placebo or E6011 in 100 mg, 200 mg, or 400/200 mg doses over multiple phases: screening, observation, double-blind treatment, open-label extension, and follow-up. During the treatment phase, participants received subcutaneous injections of either the study drug or placebo at a predetermined interval over a 22-week period.
Primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at week 12. Major secondary efficacy endpoints included ACR20 at week 24, ACR50 and ACR70 responses at weeks 12 and 24, and improvements in individual ACR components. Safety was evaluated based on adverse events, laboratory parameters, vital signs, and electrocardiogram results, among others.
In total, 190 patients (78.9% women; median age, 56 years; median disease duration, 7.1±6.85 years) across all 4 treatment groups were included in the efficacy and safety analyses (54 placebo, 28 E6011 100 mg, and 54 E6011 200 mg and 400/200 mg); 169 completed the entire planned treatment regimen and 21 discontinued during the double-blind period. Baseline demographics and mean scores for clinical measures were similar across all 4 treatment groups.
At week 12, ACR20 response rates were 37%, 39.3%, 48.1%, and 46.3% in the placebo, 100 mg, 200 mg, and 400/200 mg groups, respectively. Statistical significance was not reached in the latter two groups (P =.188 for each).
Although the study did not meet its primary endpoint, multiple secondary endpoints were met. At week 24, ACR20 responses were 35.2%, 39.3%, 53.7%, and 57.4%, respectively, with significantly higher responses in the 200 mg and 400/200 mg groups compared with placebo (P =.023 and .010, respectively). At weeks 12 and 24, ACR50 and ACR70 responses continued to improve.
Clinical parameters and laboratory biomarkers, including disease activity score in 28 joints-C-reactive protein and Clinical Disease Activity Index sequentially decreased following E6011 treatment. CD16+ monocyte levels were measured, and participants were subdivided based on CD16+ levels. Those with low monocytes demonstrated no trend in terms of ACR20 response; those with high monocytes demonstrated a “marked” dose-dependent increase in ACR20 and ACR50 response rates.
There were more adverse events in the E6011 treatment groups compared with placebo, with a dose response-related incidence of adverse events, but not treatment-related adverse events. No clinically meaningful changes in laboratory data or other safety assessments were noted.
“E6011 may represent a potential treatment option for RA patients, especially for precision medicine, by considering the baseline proportion of CD16+ monocytes,” the researchers concluded. “[F]urther evaluation in future clinical trials is warranted to confirm the therapeutic benefit of E6011.”
Disclosure: This clinical trial was supported by Eisai. Co., Ltd. Please see the original reference for a full list of authors’ disclosures.
Tanaka Y, Takeuchi T, Yamanaka H, et al. Efficacy and safety of E6011, an anti-fractalkine monoclonal antibody, in active rheumatoid arthritis patients with inadequate response to methotrexate: Results of a randomized, double-blind, placebo-controlled phase 2 study. Arthritis Rheumatol. Published online October 10, 2020.doi: 10.1002/art.41555