• Rheumatology Clinical Trials
• Rheumatoid Arthritis

Elevated expression of interleukin-20 (IL-20) and its receptors has been demonstrated in synovium from patients with rheumatoid arthritis (RA) and is thought to be implicated in the pathogenesis of RA. NNC0109-0012 is a novel human monoclonal IgG4 antibody that binds to and neutralizes the activity of IL-20. Results of a Phase 2 study, presented by Ladislav Šenolt, MD, PhD, Institute of Rheumatology, Prague, Czech Republic, suggest that IL-20 is a potential target for RA therapy.

The primary objective of this randomized multicenter, double-blind, multiple-dose, placebo-controlled Phase 2a trial was to evaluate the change in disease activity (DAS28-CRP) following 12 weeks of treatment with NNC0109-0012 in patients with active RA. Secondary objectives included EULAR and ACR20/50/70 responses and safety, pharmacokinetics (PK), pharmacodynamics (PD), safety, tolerability, and immunogenicity. Subjects were required to be aged 18 to 75 years with active RA (DAS28-CRP ≥4.5; ≥5 swollen and ≥5 tender joints of the 28-joint count), have a disease duration ≥3 months, and have been on stable methotrexate therapy (≥7.5 to ≤25 mg/week) for at least 4 weeks prior to randomization.

A total of 67 patients (mostly women, two-thirds rheumatoid factor [RF]- and anticitrullinated protein antibody [ACPA]-positive, mean DAS28-CRP score of 6.0; Table 1) with active RA were randomized to subcutaneous NNC0109-0012 3 mg/kg once weekly for 12 weeks (n=45) or placebo (n=22) along with standard methotrexate treatment and followed for an additional 13 weeks.

At 12 weeks, mean changes in DAS28-CRP were significantly greater for NNC0109-0012 compared with placebo (difference,-0.88; 95% CI for difference, −1.61 to −0.14; p=0.020). Significant reduction of disease activity (−0.5; p=0.011) was observed after 1 week and was maintained for 5 weeks after the end of treatment. The reduction in disease activity was observed primarily in RF- and ACPA-positive patients. Estimated mean difference at 12 weeks was −1.66 [−2.53; −0.79; p=0.0004] and was driven mainly by a reduction in tender and swollen joints. There were no differences for DAS28-CRP changes between anti-IL-20- and placebo-treated patients with seronegative disease.

On the secondary endpoints, treatment with NNC0109-0012 resulted in a significant percentage of subjects who achieved moderate or good EULAR response (75.5%) compared with placebo (54.5%) after 12 weeks of treatment (p=0.02). DAS28-CRP remission (≤2.6) was achieved by approximately 18% of NNC0109-0012 patients. ACR 20/50/70 responses were also significantly higher in NNC0109-0012-treated RF- and ACPA-positive patients, compared with placebo-treated patients (p=0.028, p=0.045 and p=0.018, respectively), although the trial was not powered to detect differences in ACR20/50/70 responses.

The occurrence of adverse events (AEs) was similar in both groups. There was 1 withdrawal because of AEs in the placebo group. Severe AEs were reported by 1 subject in each group. There were more infections in the active treatment group (10 events in 10 patients) compared with placebo (2 events in 1 patient), but only 3 were considered to be related to the study drug. The infections were mild and consisted of upper respiratory and urinary tract infections, bronchitis, herpes simplex, and herpes zoster (placebo). Four patients in the active treatment group experienced mild, reversible injection-site reactions. No deaths, serious AEs, or dose-limiting toxicities were reported.

• © 2012 MD Conference Express®