A Phase 2 randomised trial of safety and pharmacokinetics of IgPro20 and IgPro10 in patients with diffuse cutaneous systemic sclerosis.

Abstract

Objectives: The primary objective was the safety of subcutaneous immunoglobulin, IgPro20 (Hizentra, CSL Behring) in adults with diffuse cutaneous systemic sclerosis (dcSSc). Secondary objectives included pharmacokinetics and relative bioavailability of IgPro20, and safety and pharmacokinetics of intravenous immunoglobulin, IgPro10 (Privigen, CSL Behring).

Methods: In this prospective, multicentre, randomised, open-label, crossover Phase 2 study (NCT04137224), patients (aged ≥18 years) with dcSSc were assigned to 16 weeks of IgPro20 (0.5 g/kg/week) followed by 16 weeks of IgPro10 (2 g/kg/4 weeks over 2-5 sessions), or vice-versa. Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), infusion site reactions (ISRs), clinical tests, pharmacokinetic and bioavailability were assessed.

Results: Twenty-seven patients were randomised from 9 October 2019-31 August 2021. In total, 22 patients (81.5%) experienced 107 TEAEs (IgPro20, 49; IgPro10, 58); most were mild/moderate. Six patients (22.2%) experienced ten SAEs (IgPro20, 6; IgPro10, 4); no treatment-related SAEs and no deaths were reported. IgPro20 ISR rate was low (2 per 100 infusions). Maximum immunoglobulin G concentration (mean [standard deviation]) was numerically lower following IgPro20 (23.7 [1.2] g/l) vs IgPro10 (46.1 [1.2] g/l), as was the geometric mean dose-normalised, baseline-corrected area under the concentration-time curve from time point 0 to tau (IgPro20, 44.8 [1.4] h*g/l; IgPro10, 60.2 [1.4] h*g/l). The bioavailability of IgPro20 relative to IgPro10 was 76.1%.

Conclusion: This study shows that in patients with dcSSc, safety, pharmacokinetic and bioavailability profiles of IgPro20, and safety and pharmacokinetics of IgPro10, are similar to those observed in other approved indications.

Trial registration: https://clinicaltrials.gov, NCT04137224.