medwireNews: Phase I trial results suggest that the CD40 ligand (CD40L) inhibitor dapirolizumab pegol is well tolerated and elicits a clinical response in patients with systemic lupus erythematosus (SLE).
Previous clinical trials of the anti-CD40L antibody hu5c8 in patients with lupus nephritis “were halted because of a higher than expected occurrence of thromboembolic events,” say the study authors, noting that dapirolizumab pegol – an anti-CD40L Fab' antibody fragment conjugated to polyethylene glycol – was designed to address these safety concerns while retaining favorable pharmacokinetics.
The 32-week study involved 24 SLE patients who were positive for antidouble stranded DNA or antinuclear antibody at the time of or prior to enrolment, 16 of whom were randomly assigned to receive dapirolizumab pegol at an initial dose of 30 mg/kg followed by 15 mg/kg every 2 weeks for 10 weeks, and eight of whom received a matched placebo regimen.
None of the participants experienced serious adverse events, no deaths occurred, and there were no thromboembolic treatment-emergent adverse events (TEAEs) or laboratory findings suggestive of thromboembolic events, report the researchers in the Annals of the Rheumatic Diseases.
The most commonly reported TEAE by patients receiving dapirolizumab pegol was nasopharyngitis, experienced by 37.5% of 16 patients receiving the drug and none of the eight participants in the placebo group. Headache, upper respiratory tract infection, anemia, and diarrhea were reported by a corresponding 25.0% versus 12.5%, 18.8% versus 12.5%, 12.5% versus 0%, and 12.5% versus 0% of patients.
One participant receiving dapirolizumab pegol discontinued the trial due to an upper respiratory tract infection, but the infection was not considered to be treatment related, say Chris Chamberlain (UCB Pharma, Slough, UK) and study co-authors.
In an efficacy analysis of participants with high disease activity at baseline, the team found that 45.5% of 11 patients treated with dapirolizumab pegol and 14.3% of seven in the placebo group experienced a reduction in disease activity at week 12 according to the British Isles Lupus Assessment Group-based Composite Lupus Assessment.
Similarly, a greater proportion of participants in the dapirolizumab pegol compared with the placebo group experienced a treatment response by week 12 as indicated by the SLE Responder Index-4, at 41.7% versus 14.3%.
Although these preliminary safety and efficacy findings are “promising,” Chamberlain and colleagues note that they “must be interpreted with caution as this small, exploratory study was not powered to demonstrate statistical significance on all outcomes reported.”
They also highlight that dose effects could not be studied as only one dose was evaluated, but “a phase II dose-ranging study to better define the optimal therapeutic dose and regimen is underway.”
And the team concludes that their phase I results “support further investigation of dapirolizumab pegol as a novel treatment for SLE.”
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