fSCIG 10% in pediatric primary immunodeficiency diseases: a European post-authorization safety study
Peter Čižnár1, Marion Roderick2, Helen Schneiderova3
1Department of Paediatrics, Faculty of Medicine, Comenius University Bratislava, National Institute of Children's Diseases, Bratislava, Slovakia.
Insights
Hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% is safe and well-tolerated in children with primary immunodeficiency diseases (PIDs). Local adverse events decreased over time, with no serious safety concerns identified in this study.
Area of Science:
- Immunology
- Pediatrics
- Pharmacology
Background:
- Assessed the safety, tolerability, and immunogenicity of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% in pediatric patients with primary immunodeficiency diseases (PIDs).
- fSCIG 10% combines human immunoglobulin 10% with recombinant human hyaluronidase (rHuPH20).
Purpose of the Study:
- To evaluate the safety and tolerability of fSCIG 10% in children diagnosed with PIDs.
- To determine the incidence of noninfectious treatment-related adverse events (AEs) in pediatric PID patients receiving fSCIG 10%.
Main Methods:
- Phase 4, prospective, interventional, multicenter study (NCT03116347) involving 42 pediatric patients (aged 2 to <18 years) with PIDs.
- Patients either initiated fSCIG 10% with dose ramp-up or were pretreated.
- Primary outcome: number and rate of noninfectious treatment-related serious and severe adverse events (AEs).
Main Results:
- 49 related noninfectious adverse events (TEAEs) occurred in 15 patients, mostly mild (87.8%).
- No serious treatment-related TEAEs were reported; two severe TEAEs (infusion site pain, emotional distress) occurred in one new starter.
- Local TEAE rates were lower in pretreated patients (0.1/patient-year) vs. new starters (1.3/patient-year); no anti-rHuPH20 antibodies detected.
Conclusions:
- fSCIG 10% demonstrated a favorable safety profile in children with PIDs, with no identified safety signals.
- The incidence of local adverse events decreased over the treatment duration.
- The study supports the long-term safety of fSCIG 10% for pediatric PID patients.
Background:
The safety, tolerability, and immunogenicity of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% (dual-vial unit of human immunoglobulin 10% and recombinant human hyaluronidase [rHuPH20]) were assessed in children with primary immunodeficiency diseases (PIDs).
Methods:
This phase 4, post-authorization, prospective, interventional, multicenter study (NCT03116347) conducted in the European Economic Area, enrolled patients aged 2 to < 18 years with a documented PID diagnosis who had received immunoglobulin therapy for ≥ 3 months before enrollment. New fSCIG 10% starters underwent fSCIG 10% dose ramp-up for ≤ 6 weeks (epoch 1) before receiving fSCIG 10% for ≤ 3 years (epoch 2); patients pretreated with fSCIG 10% entered epoch 2 directly. The primary outcome was the number and rate (per infusion) of all noninfectious treatment-related serious and severe adverse events (AEs).
Results:
In total, 42 patients were enrolled and dosed (median [range] age: 11.5 [3-17] years; 81% male; 23 new starters; 19 pretreated). Overall, 49 related noninfectious, treatment-emergent AEs (TEAEs) were reported in 15 patients; most were mild in severity (87.8%). No treatment-related serious TEAEs were reported. Two TEAEs (infusion site pain and emotional distress) were reported as severe and treatment-related in a single new fSCIG 10% starter. The rate of local TEAEs was lower in pretreated patients (0.1 event/patient-year) versus new starters (1.3 events/patient-year). No patients tested positive for binding anti-rHuPH20 antibodies (titer of ≥ 1:160).
Conclusions:
No safety signals were identified, and the incidence of local AEs declined over the duration of fSCIG 10% treatment. This study supports fSCIG 10% long-term safety in children with PIDs. TRIAL REGISTRATION NUMBER (CLINICALTRIALS.GOV): NCT03116347.
