Polyvalent Human Immune Globulin: A Prospective, Open-Label Study Assessing Anti-Hepatitis A Virus (HAV) Antibody Levels, Pharmacokinetics, and Safety in HAV-Seronegative Healthy Subjects

• Published in: Advances in therapy Vol. 37; no. 5; pp. 2373 - 2389
• Main Authors: Kankam, Martin, Griffin, Rhonda, Price, Jeffrey, Michaud, Josée, Liang, Wei, Llorens, Mariona Bassas, Sanz, Ana, Vince, Bradley, Vilardell, David
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.05.2020
• Subjects: Adult; Cardiology; Dose-Response Relationship, Drug; Endocrinology; Female; Healthy Volunteers; Hepatitis A - immunology; Hepatitis A - prevention & control; Hepatitis A Antibodies - immunology; Hepatitis A virus - immunology; Humans; Immunoglobulin G - administration & dosage; Immunoglobulin G - immunology; Injections, Intramuscular; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original Research; Pharmacology/Toxicology; Prospective Studies; Research Design; Rheumatology; Hepatitis A virus; Infectious diseases; Efficacy; Intramuscular immunoglobulin; Tolerability; Safety; Pharmacokinetics
• ISSN: 0741-238X; 1865-8652; 1865-8652
• DOI: 10.1007/s12325-020-01327-9

Background Analytical data suggesting that immunoglobulin given intramuscularly (IGIM) may have reduced protection against hepatitis A virus (HAV) infection led to an update in the recommended IGIM dose (0.2 ml/kg). Methods This prospective, open-label, single-arm clinical study evaluated whether a single 0.2 ml/kg dose of IGIM provided protective levels of anti-HAV antibodies (≥ 10 mIU/ml for up to 60 days) in HAV-seronegative healthy adults. Results Of the 28 subjects enrolled and dosed, 26 (93%) completed the study. Mean uncorrected anti-HAV antibody titers peaked at 109 mIU/ml on day 5 and stayed above 10 mIU/ml through day 60 ( N  = 26). The mean uncorrected anti-HAV antibody titers had a median T max of 95.33 h, a mean C max of 118 mIU/ml, and a mean observed T half of 63.3 days; baseline-corrected titers had a median T max of 95.33 h, a mean C max of 114 mIU/ml, and a mean observed T half of 47.1 days ( N  = 27). All subjects (28/28) experienced at least 1 treatment-emergent adverse event (TEAE), with a total of 83 TEAEs reported; none was serious, and 96% (80/83) resolved without sequelae. Most (63%) events judged definitely and possibly related to study treatment involved localized pain due to intramuscular injections. There were no serious adverse events and no deaths or discontinuations due to TEAEs. Conclusions A single 0.2 ml/kg dose of IGIM provided protective anti-HAV levels for at least 60 days, with acceptable safety and tolerability profiles in healthy subjects. Uncorrected and baseline-corrected pharmacokinetic findings were similar and consistent with the corresponding sampling points in previous research. Trial Registration ClinicalTrials.gov Identifier, NCT03351933.