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CNT0675 seen as safe, but not effective in treatment of MTX-resistant RA
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In patients with rheumatoid arthritis that is refractory to methotrexate therapy, the human monoclonal antibody CNT06785 is well tolerated but does not appear to be clinically effective, according to findings.
In the randomized, double-blind, placebo-controlled, dose-ranging study conducted at various sites in Europe, Asia and Latin America, researchers evaluated adult patients with active disease who were resistant to methotrexate treatment (between 7.5 mg and 25 mg weekly). Patients were also required to have serum C-reactive protein of at least 0.8 at screening or erythrocyte sedimentation rate of at least 28 mm in the first hour at screening or baseline.
Patients were followed for 38 weeks after randomization, with a 10-week safety follow-up.
Researchers randomly assigned patients 1:1:1:1:1 to be treated with CNT06785 in doses of 15 mg, 50 mg, 100 mg or 200 mg every 4 weeks. Control group patients were treated with placebo every 4 weeks (q4w) through week 12, followed by CNTO6785 200 mg q4w from week 16 to week 28.
The primary endpoint was defined as the percentage of patients to attain ACR20 response at week 16. Major secondary endpoints were ACR50 response at week 16 and the change from baseline to week 16 in DAS28 using CRP (DAS28-CRP). Researchers monitored adverse events (AEs), clinical lab tests (hematology, serum chemistry and urinalysis) vital sign measurements, physical examinations and electrocardiograms through week 38.
Researchers found no difference in the primary endpoint of ACR 20 achievement at week 16 between placebo and any of the individual or combined CNT06785 treatment groups.
In a comparison of the percentage of responders with time, no significant differences were seen between placebo and the CNT06785 groups in the proportion of ACR20, ACR50 or ACR70 through week 32.
No difference was observed between placebo and the CNT06785 treatment groups regarding the change in DAS28-CRP between baseline and week 32 or in the percentage of patients with DAS28-CRP response. At week 16, the percentage of patients to achieve DAS28-CRP remission was numerically higher in the combined CNT06785 group (15%) vs. the placebo group (7.8%). There was no consistent dose-response relationship seen between the CNT06785 groups in terms of DAS28-CRP response or remission. In the placebo group, 3.9% of patients achieved SDAI-based ACR/EULAR remission at week 16 vs. 4.9% in the CNT06785 group. At week 32, 7.8% of placebo patients achieved SDAI-based ACR/EULAR remission vs. 12.5% in the CNT06785 group.
In terms of Boolean-based ACR/EULAR remission, 3.9% of placebo patients attained this remission at both weeks 16 and 32, while 4.4% of the combined CNT06785 groups achieved Boolean-based ACR/EULAR remission at week 16 and 7.8% achieved this goal at week 32. These differences did not reach statistical significance. No significant differences were observed between placebo and CNTO6785 in the mean change from baseline in CDAI and SDAI.
There were no dose-response correlations or specific trends seen in treatment-emergent adverse event (TEAE) profiles among the different CNT0675 treatment groups. Through week 16, all CNTO6785 groups had a higher percentage of patients with at least one TEAE. The incidence of infections was comparable across all patient groups, and reactions at the injection site were mild/moderate and did not show a dose-response.
Median blood concentration increases of CNT0675 through week 38 were nearly dose proportional after initial dosing and following multiple administrations. At week 24 and week 28, median trough concentrations were similar between groups, indicating that steady state was attained by week 24. The rate of neutralizing antidrug antibodies was 19.4% and this rate showed no association with study drug dose level.
“Despite the negative efficacy findings, CNTO6785 was well tolerated in patients with active RA. No major safety signals were detected for CNTO6785 given at doses up to 200 mg q4w SC for 28 weeks,” the researchers wrote. “The favorable safety profile of CNTO6785 suggests that it may be an appropriate candidate for indications in other autoimmune diseases.” -by Jennifer Byrne
Disclosures: Please see the full study for a list of relevant disclosures.
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Mease PJ, et al. J Rheumatol. 2017;doi:10.3899/jrheum.161238.
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