Dr. Petri has received consulting fees from GlaxoSmithKline and Human Genome Sciences (less than $10,000 each).
Systemic Lupus Erythematosus
Sifalimumab, a Human Anti–Interferon-α Monoclonal Antibody, in Systemic Lupus Erythematosus: A Phase I Randomized, Controlled, Dose-Escalation Study†
Article first published online: 28 MAR 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 65, Issue 4, pages 1011–1021, April 2013
How to Cite
Petri, M., Wallace, D. J., Spindler, A., Chindalore, V., Kalunian, K., Mysler, E., Neuwelt, C. M., Robbie, G., White, W. I., Higgs, B. W., Yao, Y., Wang, L., Ethgen, D. and Greth, W. (2013), Sifalimumab, a Human Anti–Interferon-α Monoclonal Antibody, in Systemic Lupus Erythematosus: A Phase I Randomized, Controlled, Dose-Escalation Study. Arthritis & Rheumatism, 65: 1011–1021. doi: 10.1002/art.37824
ClinicalTrials.gov identifier: NCT00482989.
- Issue published online: 28 MAR 2013
- Article first published online: 28 MAR 2013
- Accepted manuscript online: 11 FEB 2013 03:20PM EST
- Manuscript Accepted: 4 DEC 2012
- Manuscript Received: 9 MAR 2012
- MedImmune, LLC
To evaluate the safety and tolerability of multiple intravenous (IV) doses of sifalimumab in adults with moderate-to-severe systemic lupus erythematosus (SLE).
In this multicenter, double-blind, placebo-controlled, sequential dose-escalation study, patients were randomized 3:1 to receive IV sifalimumab (0.3, 1.0, 3.0, or 10.0 mg/kg) or placebo every 2 weeks to week 26, then followed up for 24 weeks. Safety assessment included recording of treatment-emergent adverse events (AEs) and serious AEs. Pharmacokinetics, immunogenicity, and pharmacodynamics were evaluated, and disease activity was assessed.
Of 161 patients, 121 received sifalimumab (26 received 0.3 mg/kg; 25, 1.0 mg/kg; 27, 3.0 mg/kg; and 43, 10 mg/kg) and 40 received placebo. Patients were predominantly female (95.7%). At baseline, patients had moderate-to-severe disease activity (mean SLE Disease Activity Index score 11.0), and most (75.2%) had a high type I interferon (IFN) gene signature. In the sifalimumab group versus the placebo group, the incidence of ≥1 treatment-emergent AE was 92.6% versus 95.0%, ≥1 serious AE was 22.3% versus 27.5%, and ≥1 infection was 67.8% versus 62.5%; discontinuations due to AEs occurred in 9.1% versus 7.5%, and death occurred in 3.3% (n = 4) versus 2.5% (n = 1). Serum sifalimumab concentrations increased in a linear and dose-proportional manner. Inhibition of the type I IFN gene signature was sustained during treatment in patients with a high baseline signature. No statistically significant differences in clinical activity (SLEDAI and British Isles Lupus Assessment Group score) between sifalimumab and placebo were observed. However, when adjusted for excess burst steroids, SLEDAI change from baseline showed a positive trend over time. A trend toward normal complement C3 or C4 level at week 26 was seen in the sifalimumab groups compared with baseline.
The observed safety/tolerability and clinical activity profile of sifalimumab support its continued clinical development for SLE.