Clinical Efficacy, Safety and Tolerability of a New Subcutaneous Immunoglobulin 16.5% (Octanorm [Cutaquig®]) in the Treatment of Patients With Primary Immunodeficiencies

Roger H Kobayashi, Sudhir Gupta, Isaac Melamed, J Fernando Mandujano, Ai Lan Kobayashi, Bruce Ritchie, Bob Geng, Thomas Prescott Atkinson, Syed Rehman, Eva Turpel-Kantor, Jiří Litzman, Roger H Kobayashi, Sudhir Gupta, Isaac Melamed, J Fernando Mandujano, Ai Lan Kobayashi, Bruce Ritchie, Bob Geng, Thomas Prescott Atkinson, Syed Rehman, Eva Turpel-Kantor, Jiří Litzman

Abstract

Introduction: Subcutaneously administered immunoglobulin (SCIG) is increasingly used to treat patients with primary immunodeficiencies (PIDs). Octanorm (marketed as cutaquig® in USA and Canada) is a new 16.5% solution of human SCIG, manufactured by a process based on that of the intravenous preparation (IVIG) octagam®. Objectives: To investigate the efficacy, safety and tolerability of octanorm in a prospective, open-label, single-arm phase 3 study involving adult and pediatric patients with PIDs (NCT01888484; clinicaltrials.gov/ct2/show/NCT01888484). Methods: Patients who were previously treated with IVIG received a total of 64 weekly SCIG infusions, including 12 weekly infusions during the wash-in/wash-out period, followed by 52 weekly infusions during the evaluation period. Results: A total of 61 patients aged 2-73 years received 3,497 infusions of octanorm. The mean dose per patient was 0.175 g/kg/infusion. The mean calculated dose conversion factor from the patients' previous IVIG dose for octanorm was 1.37. No serious bacterial infections developed during the study. The rate of other infections per person-year during the primary observation period was 3.43 (upper 95% CI 4.57). All but one non-bacterial infection were mild or moderate in intensity. IgG trough levels were constant during the course of the study. Eleven patients (18.0%) experienced 14 mild or moderate systemic adverse events (AEs) related to octanorm. The rate of related AEs per infusion was 0.004. In 76.7% of infusions, no infusion site reactions were observed and only two (0.3%) reactions were deemed severe. The incidence of site reactions decreased with successive infusions. Conclusion: The new 16.5% SCIG octanorm was shown to be efficacious in preventing infections in PIDs, and was well tolerated.

Keywords: SCIG; antibodies; immunoglobulins; infections; infusion site reactions; primary immunodeficiencies.

Figures

Figure 1
Figure 1
Study design. *Study IVIG injection was only administered to the patients participating in the PK sub-study. PKIV, PK following IVIG prior to the switch to octanorm; PKSC1, PK after the 11th infusion of octanorm; PKSC2, PK after the 28th infusion of octanorm. IVIG, intravenous immunoglobulin; PK, pharmacokinetic; SCIG, subcutaneous immunoglobulin.
Figure 2
Figure 2
Patient disposition. *One patient had no blood sampling and did not participate in the PK sub-study. †One patient did not have PK samples available from the PKSC2 sampling time point. ‡The reason for withdrawal was the patient's decision in each case. #Three patients withdrew before the start of the primary efficacy period. FAS, full analysis set; ITT, intention-to-treat; N, number of patients; PK, pharmacokinetic.
Figure 3
Figure 3
IgG concentrations over time. (A) Median trough concentrations of IgG and its subclasses after IVIG infusion (PKIV) and after octanorm infusions at 11 (PKSC1) and 28 weeks (PKSC2). For PKIV and PKSC1N = 22, for PKSC2N = 21. N, number of patients; IgG, immunoglobulin G; PKIV, PK following IVIG prior to the switch to octanorm; PKSC1, PK after the 11th infusion of octanorm; PKSC2, PK after the 28th infusion of octanorm—at steady state. (B) IgG levels over 7 days after infusion. Data are shown for the 22 patients who participated in the PK sub-study and had IgG measurements at week 28 (PKSC2).
Figure 4
Figure 4
Rate of infusion site reactions over time. (A) Rate of infusion site reactions over time. (B) Comparison of the rate of infusion site reactions in the first and last 4 weeks of the study.
Figure 5
Figure 5
Infusion flow rate and infusion site reactions. ISR, infusion site reaction.

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