Safety and neutralizing rabies antibody in healthy subjects given a single dose of rabies immune globulin caprylate/chromatography purified

Kim Hanna, Maria Cristina Cruz, Elsa Mondou, Edward Corsi, Peter Vandeberg, Kim Hanna, Maria Cristina Cruz, Elsa Mondou, Edward Corsi, Peter Vandeberg

Abstract

Background: Rabies immune globulin (RIG) and vaccination series are necessary for postexposure prophylaxis. A new formulation of RIG (human) purified by caprylate/chromatography (RIG-C) was evaluated.

Trial registration: ClinicalTrials.gov identifier: NCT02139657.

Materials and methods: This open-label, single-arm study in healthy subjects evaluated neutralizing rabies antibody concentrations produced from a single 20 IU/kg intramuscular (IM) dose of RIG-C as measured by rapid fluorescent focus inhibition test (50% neutralization endpoint) 1-hour postdose and on days 1, 2, 4, 6, 8, 10, 14, 18, and 21.

Results: Twelve subjects were enrolled into the study. No discontinuations, serious adverse events (AEs), or treatment-emergent clinically significant changes in laboratory parameters were observed. All AEs resolved and were mild except 1 moderate AE of oropharyngeal pain. Injection site pain (4 subjects) was most commonly reported. RIG-C produced a rapid increase in neutralizing rabies antibody: mean value 0.113 IU/mL at 24 hours after IM injection, peak on day 4 (0.132 IU/mL), persisting through day 21 (0.116 IU/mL). The mean reciprocal titer was 11.5 by day 2; the peak value of 12.1 was achieved on day 4; and a mean value ≥10.6 was maintained through day 21.

Conclusion: RIG-C was well tolerated and provided neutralizing rabies antibodies, which combined with vaccine series after rabies exposure, should result in effective prophylaxis per World Health Organization/Centers for Disease Control and Prevention guidelines.

Keywords: GTI1301; RIG-C; prophylaxis; rabies; rabies immune globulin; rabies neutralizing antibody titers.

Conflict of interest statement

Disclosure All the authors are employees of Grifols and report personal fees from Grifols during the conduct of the study. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Study design. Notes: Written informed consent was obtained from all prospective healthy subjects at the screening visit prior to performing any study procedures. At the screening visit, subjects were screened by physical examination and laboratory assessments. Eligibility for the study was determined by the protocol inclusion and exclusion criteria over a screening period of up to 21 days. Subjects who met all eligibility criteria received a single dose of RIG-C (20 IU/kg) at the baseline/treatment, study day 0 visit. Subjects then entered a postadministration follow-up period of 21 days, with clinic visits on study days 1, 2, 4, 6, 8, 10, 14, 18, and 21. The total duration of study participation for subjects who completed the study was up to 43 days. Abbreviations: IM, intramuscular; RIG-C, rabies immune globulin purified by caprylate/chromatography.
Figure 2
Figure 2
Anti-rabies virus antibody concentrations by RFFIT (IU/mL) following a single IM dose of RIG-C (mean ± SD). Abbreviations: RFFIT, rapid fluorescent focus inhibition test; IM, intramuscular; RIG-C, rabies immune globulin purified by caprylate/chromatography; SD, standard deviation.
Figure 3
Figure 3
Reciprocal of anti-rabies virus antibody titer by RFFIT following a single IM dose of RIG-C (mean ± SD). Abbreviations: RFFIT, rapid fluorescent focus inhibition test; IM, intramuscular; RIG-C, rabies immune globulin purified by caprylate/chromatography; SD, standard deviation.
Figure 4
Figure 4
Reciprocal of anti-rabies virus antibody titer following a single IM dose of RIG-C or RIG-S/D product (mean ± SD). Notes: This graph depicts the mean (SD) RFFIT results for both RIG-C (black diamond) and RIG-S/D (gray square) products. Data for RIG-S/D were derived from the Bayer data on file 1996, Report MRR 1321 of 8 healthy adult subjects who received a 20 IU/kg IM dose of RIG-S/D in two injections. Abbreviations: IM, intramuscular; RIG-C, rabies immune globulin purified by caprylate/chromatography; RIG-S/D, rabies immune globulin purified by solvent/detergent; SD, standard deviation; RFFIT, rapid fluorescent focus inhibition test.

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