Trial establishes safety, efficacy of human rabies immune globulin in children
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A phase 4 trial demonstrated that a human rabies immune globulin was safe and effective in children when given as part of rabies post-exposure prophylaxis, researchers reported in Human Vaccines & Immunotherapeutics.
Rabies is rare in the United States, with just 25 cases reported from 2009 to 2018, according to the CDC. During that time, just three cases occurred in children younger than age 18 years, including at least two that were caused by a bite from a bat, which has been the most common cause of rabies over the past 60-plus years in the U.S.
Globally, however, WHO estimates that 40% of rabies cases occur among children aged younger than 15 years, with most encounters caused by dog bites, according to a news release publicizing the results of the new study. Once clinical symptoms occur, rabies is almost always fatal.
Currently, CDC and AAP treatment recommendations call for postexposure prophylaxis (PEP) combining human rabies immune globulin and a series of four doses of rabies vaccine given on days 0, 3, 7 and 14.
In their study, Nicholas Hobart-Porter, DO, an emergency medicine physician at Arkansas Children’s Hospital, and colleagues enrolled 30 trial participants aged 17 years or younger with a confirmed rabies exposure who had received human rabies immune globulin (HRIG150; KEDRAB 150 IU/mL) as part of rabies PEP.
Following the administration of KEDRAB, study participants were evaluated through follow-up visits on days 3, 7 and 14, whereas follow-up phone calls occurred on days 1, 28, 56 and 84.
“Diary cards” were given to the participants’ parents and guardians following the administration of KEDRAB, and guardians were instructed to record information on any adverse events (AEs) that may have occurred.
Following the 84-day trial, 28 patients completed the trial. Two participants were lost to follow-up. The mean age of participants was 7.45 years and ranged in age from 0.5 to 14.9 years. A majority of the patient population was white (21; 70%), seven (23.3%) were Black and two (6.7%) were Asian.
Among all 30 participants who were suspected to have been exposed to rabies, three (10%) were from animals that were confirmed to have rabies, whereas the others were associated with confirmed negative animals. All participants were free of rabies on day 14 of the trial, and active rabies infection did not develop in any participant.
No participant reported a severe AE. Following 14 days of the trial, 21 of the 30 participants (70%) experienced a treatment-emergent AE, with 57 reported overall, all of which were reported to be mild. The most common reported AE was injection site pain.
“We conclude that HRIG150 is appropriate for use as a lifesaving component of PEP in pediatric patients,” the authors wrote.
According to the new release, it was the first trial to demonstrate that an HRIG was safe and effective in children when administered promptly as a part of the rabies PEP process.
“Evidence from this KEDRAB U.S. Pediatric Trial conrms that this product addresses an unmet need in children who may have been exposed to rabies, and gives health care providers condence when preventing this deadly condition in countless numbers of young patients across the United States,” Hobart-Porter said in a release.
Perspective
Back to TopRichard F. Jacobs, MD
The study by Hobart-Porter and colleagues provides an assessment in the use of HRIG150 in children aged younger than 17 years that required rabies prophylaxis (PEP) for at-risk animal bites. The patients chosen met criteria for the need of PEP to include HRIG150 and rabies vaccine, according to established clinical guidelines.
The primary purpose of this phase 4, two-center, open-label, single-arm clinical trial was to establish the safety of the HRIG150 administration, according to established guidelines for site and procedure of administration based upon on adult trials. They also studied the immunogenicity of the concomitant administration of rabies vaccine given concurrently with HRIG150.
Although the authors state that they also established efficacy, this was an open and single-arm trial, and although there were no rabies-related deaths, this study was not a randomized, controlled trial. That is understandable considering the potential severity of the disease and established current guidelines for use of HRIG and vaccine in potentially high-risk exposures to potentially rabid animals.
This trial does provide valuable information on the safety of HRIG150. There were no serious AEs and no negative impact on the immune responses to the vaccine. Both endpoints support adult data and provide highly valuable support for the use of HRIG150 in children. The AEs observed were all mild and included injection site pain (five; 16.6%), injection site erythema (one; 3.3%), fatigue (two; 6.7%), and one each (3.3%) of vomiting, pyrexia, body temperature elevation and headache.
These are very common mild AEs for almost all injectable vaccines and immune globulins. Like so many drugs, vaccines and biologics used in humans, a significant body of evidence for safety and immunogenicity is available in adults.
The availability of data in children is always needed and valuable from such clinical trials to establish the safe use of these products. As a wise pediatrician once said, “Kids are not just little adults when it comes to drugs, vaccines and other products.” This study should give reassurance to the large number of physicians, patients and families who are recommended to receive PEP for a rabies exposure.
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