Elsevier

International Immunopharmacology

Volume 3, Issue 9, September 2003, Pages 1325-1333
International Immunopharmacology

Comparison of the efficacy of IGIV-C, 10% (caprylate/chromatography) and IGIV-SD, 10% as replacement therapy in primary immune deficiency: A randomized double-blind trial

https://doi.org/10.1016/S1567-5769(03)00134-6Get rights and content

Abstract

A novel method of large-scale chromatography has been developed to improve recovery and purity of immunoglobulin G (IgG) from pooled plasma. The current study compares safety, toxicity and efficacy of two intravenous immunoglobulin products: a novel formulation, IGIV caprylate/chromatography (IGIV-C; Gamunex™, 10%) and a licensed solvent/detergent-treated product, Gamimune®N, 10% (IGIV-SD). The study, a randomized, double-blind, parallel group, therapeutic equivalence trial, was conducted at 25 treatment centers in Canada and the United States. Patients (n=172) having confirmed chronic primary immunodeficiency (PID), aged 1–75 years, and receiving IGIV therapy were enrolled. For 9 months, patients were treated with IGIV-C or IGIV-SD in accordance with the patient's individualized treatment regimen utilized before study entry. The primary endpoint was the proportion of patients with ≥1 validated acute sinopulmonary infection during the treatment period. Secondary endpoints included the proportion of patients with all infections, time to first infection, annual infection rates, lung function parameters, infusion-related safety and viral safety. The annual validated infection rate in the IGIV-C group was 0.18 compared to 0.43 in the IGIV-SD group (p=0.023). Nine patients receiving IGIV-C experienced validated infections, compared to 17 patients in IGIV-SD group (p=0.06). Acute sinusitis (validated plus clinically defined) was less frequent in the IGIV-C group (p=0.012). Presence of bronchiectasis did not affect efficacy. Adverse reactions were similar in frequency and severity in both groups. No evidence of viral transmission was observed. IGIV-C appears to be superior to IGIV-SD in preventing validated sinopulmonary infections, especially acute sinusitis, in patients with PID.

Introduction

Immunoglobulin G (IgG) has been traditionally manufactured from pooled plasma for replacement therapy in patients with primary immunodeficiency (PID). Advances in preparation of IgG suitable for intravenous infusions (IGIV) permitted delivery of larger doses, which resulted in improved protection from infection [1]. A novel method of large-scale chromatography, which uses caprylate for purification and viral inactivation, has recently been developed to improve the recovery and purity of IgG from pooled plasma [2], [3], [4]. The intravenous immunoglobulin product resulting from this novel preparation has been named IGIV-C (Gamunex™, 10%).

Although IGIV has been manufactured using different methods, it is widely assumed that all IGIV preparations are similar. However, the efficacy and toxicity of different IGIV preparations have previously never been compared directly. This prospective, randomized, double-blind, controlled and statistically powered study compares for the first time the safety, toxicity and efficacy of two intravenous immune globulin products: the novel formulation (IGIV-C) and a licensed solvent/detergent-treated product (IGIV-SD; Gamimune®N, 10%).

Section snippets

Subjects

Twenty-five centers in the USA and Canada enrolled 172 patients, aged 1–75 years, who were receiving stable IGIV replacement therapy and had a confirmed chronic primary humoral immune deficiency as defined by the World Health Organization [5]. All study sites had Institutional Review Board approval. Patients had medical records available for retrospective review for at least 3 months prior to study entry and at least one documented IgG trough level of >390 mg/dl during the previous 6 months

Patient enrollment and compliance

A total 172 patients were randomly assigned to receive IGIV-C (n=87) or IGIV-SD (n=85). The study period, first patient's first visit to last patient's last visit, spanned from March 1999 to June 2000. Common variable immunodeficiency was the most common PID (Table 1). In each group, 73 patients were valid for per-protocol efficacy analysis.

Demographic data were comparable for both groups (Table 2). Mean IGIV dosages prior to the study were similar and most patients were on a 4-week schedule.

Discussion

Immunoglobulin preparations pooled from human blood were first used in the early 1950s to treat primary immunodeficiency conditions. Early preparations required intramuscular injections, which delivered limited amounts of antibodies. Consequently, serum concentrations of IgG remained unchanged and infection control was suboptimal [9]. The introduction of immunoglobulin preparations suitable for intravenous administration permitted replacement to normal serum IgG levels resulting in a dramatic

Acknowledgements

The authors thank Dr. Joe Kiss, Institute for Transfusion Medicine, Pittsburgh, PA, for in-depth analysis of Coombs' reactivity, Dr. Derek Stephens, Hospital for Sick Children, Toronto, ON, and Drs. Keith Bangerter and Lawrence Schwartz for statistical analysis.

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This study (Identifier 100175) was funded by Bayer Healthcare, Biological Product Division, Research Triangle Park, NC, as part of the clinical development of Gamunex™, 10%.

1

The IGIV-C in PID Study Group includes Mark Stein, MD, Allergy Associates of the Palm Beaches, North Palm Beach, FL; Donald Stark, MD, Vancouver, BC; Maria Louisa Ermitano, LSU Health Sciences Center, New Orleans, LA; Anne Desroches, MD, Hopital Ste. Justine, Montreal, Quebec; Bruce Mazer, MD, Montreal Children's Hospital, Quebec; Joseph Church, MD, Children's Hospital of Los Angeles, CA; Zuhair Ballas, MD, University of Iowa Hospitals and Clinics, Iowa City, IA; Alexandra Filipovich, MD, Children's Hospital Medical Center, Cincinnati, OH; Gilbert Friday, MD, Children's Hospital of Pittsburgh, PA; Donatella Graffino, MD, Asthma, Allergy and Sinus Center of New Jersey, Morristown, NJ; Melvin Haysman, MD, Allergy Research of Savannah, GA; Alan Knutsen, MD, St. Louis University Health Sciences Center, St. Louis, MO; Wendel Richmond, MD, Oakbrook, IL; Arye Rubinstein, MD, Albert Einstein College of Medicine, Bronx, NY; Frederick Marquinez, MD, Mogadore, OH; Don McNeil, MD, Columbus, OH; Suzanne Skoda-Smith, MD, University of Florida, Gainesville, FL.

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