A multicentre, prospective, non-randomized, sequential, open-label trial to demonstrate the bioequivalence between intravenous immunoglobulin new generation (IGNG) and standard IV immunoglobulin (IVIG) in adult patients with primary immunodeficiency (PID) - 05/07/17

Doi : 10.1016/j.revmed.2017.05.009

J.-F. Viallard ^a,^⁎ , J.-P. Brion ^b, M. Malphettes ^c, I. Durieu ^d, M. Gardembas ^e, N. Schleinitz ^f, C. Hoarau ^g, E. Lazaro ^a,^h, S. Puget ⁱ
^a Internal Medicine Unit, Haut-Lévêque Hospital, 5, avenue de Magellan, 33604 Pessac, France
^b Infectious Disease, Albert-Michallon Hospital, Grenoble, France
^c Clinical Immunology, Saint-Louis Hospital, Paris, France
^d Medicine Unit, Lyon Sud Hospital, Pierre-Bénite, France
^e Hematology Unit, Hôtel-Dieu Hospital, Angers, France
^f Medicine Unit, Conception Hospital, Marseille, France
^g Immunology Unit, Bretonneau Hospital, Tours, France
^h Internal and Infectious Disease Department, Centre François-Magendie, Pessac, France
ⁱ LFB BIOMEDICAMENTS, Immunology Therapeutic Unit, Courtabœuf, France

^⁎Corresponding author.

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Abstract

Objectives

To demonstrate the bioequivalence between 2 intravenous immunoglobulin (IVIG) preparations, TEGELINE^® and ClairYg^®, a ready-to-use 5% IVIG, in primary immunodeficiency (PID). Secondary objectives were to assess the efficacy, safety and pharmacokinetics of ClairYg^®.

Methods

Twenty-two adult PID patients receiving stable doses of TEGELINE^® (5% lyophilized IVIG) were switched to ClairYg^® for 6 months. ClairYg^® was administered under the same conditions as TEGELINE^®, either every 3 or 4 weeks. The primary endpoint was mean average total IgG trough level at steady state with ClairYg^® versus TEGELINE^®. Clinical efficacy was also assessed in terms of infections and associated events.

Results

Bioequivalence was established with a mean average total IgG trough level at steady state being 8.05g/L with TEGELINE^® and 9.17g/L with ClairYg^® (i.e. geometric mean for the difference between ClairYg^® and TEGELINE^® was 1.136; [90% CI: 1.092–1.181] P<0.001), within the pre-specified margin to establish bioequivalence (0.80–1.25). Total IgG trough levels remained clinically adequate (>4–6g/L) throughout the study. No patient was hospitalized for infection or had serious bacterial infections while receiving ClairYg^®. The median annualized infections rate per patient was similar for both products: 4.35 [0; 21.8] for TEGELINE^® and 4.30 [0; 15.1] for ClairYg^®. Infections were less common with higher IgG trough levels (>8.16g/L). ClairYg^® showed good safety, in particular good hepatic and renal tolerance, and did not induce hemolysis. ClairYg^® pharmacokinetics profile was comparable to that of TEGELINE^®.