Safety and efficacy of rabies immunoglobulin in pediatric patients with suspected exposure

ABSTRACT

Rabies is a deadly viral zoonosis with global disease burden. Following exposure to a rabid animal, post-exposure prophylaxis (PEP) is the standard of care for unvaccinated persons. Despite the large proportion of pediatric cases, limited safety and efficacy data exist for use in pediatric patients. We report the safety, efficacy, and immunogenicity of a phase 4, prospective, 2-center, open-label, single-arm clinical trial evaluating human rabies immunoglobulin (HRIG150; KEDRAB 150 IU/mL) as part of PEP in patients (aged <17) with suspected or confirmed rabies exposure, where PEP was indicated. Thirty participants received 20 IU/kg HRIG150 infiltrated into the detectable wound site(s), with any remainder injected intramuscularly, concomitantly with the first of a 4-dose series (days 0, 3, 7, and 14) of rabies vaccine. Rabies virus neutralizing antibody (RVNA) titers and tolerability were assessed on day 14 following administration. Participant safety was monitored for 84 days. No serious adverse events, rabies infections, or deaths were recorded. Twenty-one participants (70.0%) experienced a total of 57 treatment-emergent adverse events (TEAEs) within 14 days following administration. Twelve participants (40.0%) experienced a total of 13 adverse events deemed treatment related. All TEAEs were mild in severity. On day 14, 28 participants (93.3%) had RVNA levels of ≥0.5 IU/mL (mean±standard deviation: 18.89 ± 31.61). These results demonstrate that HRIG150 is well tolerated and effective in pediatric patients as a component of PEP. To the authors’ knowledge, this study is the first to establish pediatric safety and efficacy of HRIG in the US.

KEYWORDS:

• Pediatrics
• clinical trial
• infectious disease
• wound treatment
• immunoglobulin
• post-exposure prophylaxis
• rabies
• vaccine
• zoonotic disease

Acknowledgments

The authors thank The Medicine Group, LLC (New Hope, PA, USA) for providing editorial support in accordance with Good Publication guidelines.

Abbreviations

ACIP	=	Advisory Committee on Immunization Practice
AE	=	Adverse event;
BMI	=	Body mass index
CDC	=	Centers for Disease Control and Prevention
HRIG150	=	KEDRAB™ human rabies immunoglobulin 150 IU/mL
IM	=	Intramuscular
KSU	=	Kansas State University
PEP	=	Post-exposure prophylaxis
RIG	=	Rabies immunoglobulin
IU	=	International unit
RVNA	=	Rabies virus neutralizing antibody
SAE	=	Serious adverse event
SD	=	Standard deviation
TEAE	=	Treatment-emergent adverse event
WHO	=	World Health Organization

Disclosure of potential conflicts of interest

Nicholas Hobart-Porter, DO: No conflicts of interest

Michal Stein, MD: Employee of Kamada Ltd, manufacturer of product investigated

Naveh Toh, MD: Employee of Kamada Ltd, manufacturer of product investigated

Novinyo Amega, MD: Employee of Kedrion Biopharma Inc., US distributor of product investigated

Huy-Binh Nguyen, PhD: Employee of Kedrion Biopharma Inc., US distributor of product investigated

James Linakis, PhD, MD: No conflicts of interest

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

Research funding provided by Kamada Ltd. and Kedrion Biopharma Inc.