Efficacy, Safety and Tolerability of a New 10% Intravenous Immunoglobulin for the Treatment of Primary Immunodeficiencies

Abstract

We report here the results of a phase 3 study to assess the efficacy, safety, and tolerability of GC5107, a new 10% liquid intravenous immunoglobulin (IVIG) in preventing serious bacterial infections in patients with primary immunodeficiency (ClinicalTrials.gov: NCT02783482). Over a 12-month study period, 49 patients aged 3 to 70 years with a confirmed diagnosis of primary immunodeficiency received GC5107 at doses ranging from 319 to 881 mg/kg body weight every 21 or 28 days, according to their previous IVIG maintenance therapy. A total of 667 infusions of GC5107 were administered comprising a total of 45.86 patient-years of treatment. A single acute serious bacterial infection occurred during the study, resulting in an incidence of 0.02 events per patient-year (upper 99% one-sided confidence interval limit: 0.21), meeting the prespecified primary efficacy endpoint. The mean incidence of infections other than acute serious bacterial infections was 2.9 infections per patient-year. Efficacy was also demonstrated by the low mean annualized rate of hospitalizations due to infection (0.1 day) and the mean annualized duration of hospitalizations (0.1 day). The mean rate of intravenous and oral antibiotic use was 0.1 day and 13.2 days, respectively. There was a mean of 7.1 days of missed work, school, or daycare days. The proportion of infusions with temporally associated adverse events (TAAEs) occurring during or within 72 hours after GC5107 infusion was 0.24 (upper 95% one-sided confidence interval limit: 0.31), meeting the pre-specified primary safety endpoint. Overall, 149 of 667 infusions (22%) were associated with TAAEs. The most common TAAE was headache, reported by 49% of patients. More than 98% (731/743) of all adverse events that occurred throughout the 12-month study period were mild or moderate. More than 98% of infusions were completed without discontinuation, interruption or rate reduction. There were no treatment-emergent serious adverse events related to GC5107 or study discontinuations due to an adverse event. Overall, pharmacokinetic parameters for GC5107 were within the range of those reported in studies of other marketed IVIG products. Results of the present study demonstrate that GC5107 is an effective, safe and well-tolerated treatment for patients with primary immunodeficiency.

Keywords: GC5107; IVIG; IgG; immune globulin intravenous; immunoglobulin replacement therapy; inborn errors of immunity; intravenous immune globulin; primary immunodeficiency disease.

Conflict of interest statement

AE has participated in advisory boards for ALK Abello, AstraZeneca, Aralez, Bausch Health, LEO Pharma, Merck, Novartis, and Pfizer; has served as a speaker for ALK Abello, The ACADEMY, Aralez, AstraZeneca, Medexus, and Mylan; and has been a consultant to Bayer LLC and Regeneron. Her institution has received research grants from ALK Abello, Aralez, AstraZeneca, Bayer LLC, GC Pharma, Medexus, Novartis, Sanofi and Regeneron. WL has served as a consultant for Accordant, BioCryst, Biomarin, CSL Behring, Express Scripts, Fresenius Kabi, Intellia, Kalvista, Magellan, Optum, Pharming, Pharvaris, and Shire/Takeda; serves as a speaker for BioCryst, CSL Behring, Pharming, Shire/Takeda, Grifols, Astra Zeneca, Sanofi/Regeneron and GSK; and receives grants or research support from ALK, BioCryst, CSL Behring, Gossamer, GC Pharma, Grifols, Ionis, Kalvista, Kedrion, Shire/Takeda and Therapure. He is a member of the US Hereditary Angioedema Association Medical Advisory Board. RW serves as an investigator for CSL Behring, Grifols, Kedrion, GC Pharma, Takeda, and TherapureBio; serves as a consultant for ADMA Biologicals, Grifols, GC Pharma, Takeda, and TherapureBio; and serves as a speaker for CSL Behring, Grifols, and Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from GC Pharma, Korea. The funder was involved in the study design, analysis and interpretation of data, review of the manuscript, and the decision to submit the manuscript for publication.

Copyright © 2021 Perez, Hébert, Ellis, Alpan, Lumry, Shapiro, Suez, Mandujano and Wasserman.

Figures

Figure 1

Subject disposition. *Includes subjects who were re-screened. †Six of the 24 screen failures (5 subjects) were subsequently re-screened and enrolled in the study. ‡Withdrawal of consent (n = 2); withdrawal by sponsor due to melanoma diagnosis (n = 1). §Inability to obtain IV access.