Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MDX-1100, A Fully Human Anti-CXCL10 Monoclonal Antibody, in Combination with Methotrexate (MTX) in Patients with Rheumatoid Arthritis (RA)
Yellin1, M., Paliienko2, I., Balanescu3, A., Vizir4, V., Ter-Vartanian5, S., Tian1, J., Zhu1, X.
Medarex Inc, Bloomsbury, NJ
Bogomolets National Medical University, Kyiv, Ukraine
Sf. Maria Hospital, Bucharest, Romania
Zaporizhya State Medical University, Zaporizhya, Ukraine
Kyiv Central Municipal Clinical Hospital, Kyiv, Ukraine
M. Gorky Donetsk National Medical University, Donetsk, Ukraine
Iasi Rehabilitation Clinical Hospital, Iasi, Romania
CXCL10 (IP-10) is a chemokine that promotes directed migration of activated T cells and monocytes by binding to the cell surface receptor CXCR3. Both CXCL10 and CXCR3 are abundantly expressed in rheumatoid arthritis synovium and may play a role in disease pathogenesis. MDX-1100 neutralizes CXCL10 and has been well tolerated in Phase 1 studies. This study evaluated the efficacy and safety of repeat dosing of MDX-1100 in patients with RA who had an inadequate response to methotrexate.
70 patients with active RA (>= 6 tender and >= 6 swollen joints) on stable doses of MTX (10 to 25 mg weekly) were randomized to receive every other week intravenous doses of either placebo (n=35) or MDX-1100 10 mg/kg (n=35) × 6. The primary endpoint was the ACR20 response rate at Day 85. Patients were followed for safety to study Day 141.
The MDX-1100 and placebo cohorts were well balanced with respect to mean age, sex, disease duration, baseline corticosteroid and MTX doses, and rheumatoid factor (RF) status. All but one subject was anti-TNF treatment naïve and all subjects were white. At Day 85 the ACR20 response rate was significantly higher for MDX-1100 treated patients than for placebo treated patients (54% versus 17%; p-value = 0.0024). The ACR20 response rate showed a statistically significant separation between MDX-1100 and placebo treatment at every time point from Day 43 through Day 85. The ACR50 and ACR70 response rates at Day 85 were numerically higher in the MDX-1100 cohort but did not achieve statistical significance between the 2 cohorts: 9% versus 3% for ACR50 and 3% versus 0% for ACR70. Overall, 51.4% (n=18) of MDX-1100 treated patients and 30.3% (n=10) of placebo treated patients experienced at least 1 adverse event (AE). With 2 exceptions, AEs were mild or moderate in severity (Grade 1 or 2). One patient in the MDX-1100 cohort experienced a grade 3 infusion reaction (bronchospasm) and one patient in the placebo cohort died suddenly, presumably of cardiac causes. The MDX-1100 infusion was generally well tolerated and did not require pre-medication. The infection rate was similar between the MDX-1100 and placebo cohorts (8.6% vs. 12.1%).
MDX-1100 was well tolerated and associated with a statistically significant increase in ACR20 responses compared to placebo. These results demonstrate that the CXCL10-CXCR3 pathway plays important roles in RA pathogenesis and provide rationale for the continued development of MDX-1100.
To cite this abstract, please use the following information:
Yellin, M., Paliienko, I., Balanescu, A., Vizir, V., Ter-Vartanian, S., Tian, J., et al; A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MDX-1100, A Fully Human Anti-CXCL10 Monoclonal Antibody, in Combination with Methotrexate (MTX) in Patients with Rheumatoid Arthritis (RA) [abstract]. Arthritis Rheum 2009;60 Suppl 10 :414