medwireNews: The type I interferon (IFN) inhibitor JNJ-55920839 is well tolerated and has demonstrated preliminary efficacy against systemic lupus erythematosus (SLE) in a phase 1 trial, researchers report.
“JNJ-55920839, a fully human immunoglobulin G1 κ monoclonal antibody targeting multiple IFNα subtypes and IFNω, was developed to explore the clinical benefits of specifically neutralising the activity of these IFNs in participants with SLE with an elevated type I IFN signature,” say Marc Chevrier (Janssen, Spring House, Pennsylvania, USA) and co-investigators.
The first-in-human study was conducted in two parts; part one involved 48 healthy volunteers who were treated with single ascending doses of intravenous JNJ-55920839 (0.3–15.0 mg/kg) or a single subcutaneous administration of 1.0 mg/kg, and part two involved 26 patients with mild-to-moderate SLE and a positive lupus type I IFN signature score who were given multiple 10.0 mg/kg doses of intravenous JNJ-55920839 or placebo.
In part one, the investigators say that the drug “showed linear pharmacokinetics” over the intravenous dose range studied, and “had a similar mean half-life following intravenous and subcutaneous administration.”
As reported in The Lancet Rheumatology, JNJ-55920839 was well tolerated following single-dose administration in healthy participants, with no serious adverse events, no infusion reactions, and no injection site reactions attributed to the study drug. Chevrier and team remark that infections were the most frequently occurring adverse event during an average 12.4 weeks of follow-up, with “a possible dose response” seen with intravenous dosing. Rates of infections and infestations were 17% in the 0.3 mg/kg, 3.0 mg/kg, and 15 mg/kg arms, 33% in the 1.0 mg/kg group, and 67% in the 10 mg/kg arm.
In part two, treatment-emergent infections and infestations were more common among the 18 SLE patients treated with JNJ-55920839 compared with the eight given placebo, at rates of 50% and 13%, respectively.
Noting that the “small number of participants studied […] limits the conclusions that can be made,” Chevrier et al say that “[i]ncreased rates of infection in both parts of the study require additional investigation to understand whether the risk of infection is increased with JNJ-55920839.”
The team also carried out an exploratory analysis of clinical response in evaluable patients, finding that 31.0% of SLE patients treated with JNJ-55920839 achieved an SRI-4 response between baseline and day 100, compared with none of those given placebo. Moreover, patients given the drug had a median improvement in SLEDAI-2K score of 22.5%, compared with 0.0% in the placebo arm.
“These observations warrant additional study of JNJ-55920839, including dose and regimen for the treatment of SLE,” conclude the study authors.
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