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. 2024 Sep 17;20(1):47.
doi: 10.1186/s13223-024-00904-9.

fSCIG 10% in pediatric primary immunodeficiency diseases: a European post-authorization safety study

Peter Čižnár  1 , Marion Roderick  2 , Helen Schneiderova  3 , Miloš Jeseňák  4 , Gergely Kriván  5 , Nicholas Brodszki  6 , Stephen Jolles  7 , Charles Atisso  8 , Katharina Fielhauer  9 , Shumyla Saeed-Khawaja #  8 , Barbara McCoy  9 , Leman Yel #  10   11
Affiliations

fSCIG 10% in pediatric primary immunodeficiency diseases: a European post-authorization safety study

Peter Čižnár et al. Allergy Asthma Clin Immunol. .

Abstract

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.

Keywords: Hyaluronidase; Immunoglobulins; Inborn errors of immunity (IEI); Patient safety; Pediatrics; Primary immunodeficiency diseases; Subcutaneous.

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Conflict of interest statement

PC has received speaker honoraria from Ewopharma and Takeda. MR and HS have nothing to disclose. MJ has received honoraria, consultancy, and speaker fees from ALK, CSL Behring, Ewopharma, GSK, Novartis, Sanofi-Genzyme, Stallergenes Greer, and Takeda, and has served as a principal investigator for trials sponsored by BioCryst, Octapharma, Pharming, and Takeda. GK has received support from Baxter/Baxalta/Shire/Takeda, Biotest, CSL Behring, Grifols, Kedrion, LFB, MSD, Novartis, Octapharma, and Sanofi for projects, advisory boards, symposia, clinical studies, and trials. NB has received honoraria from Baxalta/Shire/Takeda, BioCryst, and Octapharma for advisory boards, trials, and speaker fees. SJ has received support from Binding Site, Biotest, BPL, CSL Behring, Grifols, GSK, LFB, Octapharma, Pharming, Sanofi, Sobi, Takeda, UCB Pharma, Weatherden, and Zarodex for projects, advisory boards, meetings, studies, symposia, and clinical trials. CA is an employee of Takeda Development Center Americas, Inc. and a Takeda shareholder. KF and BM are employees and shareholders of Baxalta Innovations GmbH, a Takeda company. SSK was an employee of Takeda Development Center Americas, Inc. and a Takeda shareholder at the time of the study. LY is a Takeda shareholder, and was an employee of Takeda Development Center Americas, Inc. at the time of the study.

Figures

Fig. 1
Fig. 1
Study design. Epoch 1 (fSCIG 10% ramp-up): ≤ 6 weeks. Epoch 2 (fSCIG 10% treatment): 1–3 years. Epoch 3 (safety follow-up): up to 1 year. Ab, antibody; AE, adverse event; fSCIG, hyaluronidase-facilitated subcutaneous immunoglobulin; IVIG, intravenous immunoglobulin; rHuPH20, recombinant human hyaluronidase; SAE, serious adverse event; SCIG, subcutaneous immunoglobulin
Fig. 2
Fig. 2
Patient disposition. †22 of 23 new starters completed epoch 1, and continued and completed epoch 2. fSCIG, hyaluronidase-facilitated subcutaneous immunoglobulin
Fig. 3
Fig. 3
Mean (SD) concentration–time profile of total serum IgG trough levels over time. E2M0, epoch 2 month 0; E2M6, epoch 2 month 6; E2M12, epoch 2 month 12; IgG, immunoglobulin G; SD, standard deviation
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