. Mild is defined as transient discomfort that resolves spontaneously or with minimal intervention; moderate is defined as limited impairment of function and resolves spontaneously or with minimal intervention with no sequelae. No serious adverse reactions occurred during the HYQVIA clinical trials.
Table 4 Adverse Reactionsa in greater than 5% of Subjects Associated with Infusions of HYQVIA vs. Immune Globulin Infusion 10% (Human) (IGIV) Given Intravenously HYQVIA IGIV Given Intravenously
Adverse Reactionsb Number of Subjects (%)
N= 81 Number of Adverse Reactions per Infusion (Ratec)
N = 1129 Number of Subjects (%)
N=87 Number of Adverse Reactions per Infusion (Rate)
N = 365
Local ARs
42 (51.9%)
234 (0.21)
4 (4.6%)
4 (0.01)
Systemic ARs
55 (67.9%)
222 (0.20)
54 (62.1%)
154 (0.42)
Headache
17 (21%)
40 (0.04)
22 (25.3%)
42 (0.12)
Fatigue
9 (11.1%)
16 (0.01)
8 (9.2%)
10 (0.03)
Nausea
6 (7.4%)
12 (0.01)
10 (11.5%)
10 (0.03)
Pyrexia
6 (7.4%)
11 (0.01)
6 (6.9%)
7 (0.02)
Vomiting
6 (7.4%)
11 (0.01)
5 (5.7%)
7 (0.02)
a Causally related adverse events and/or temporally associated adverse events occurring within 72 hours.
b Excluding infections
c Rate = total number of events divided by total number of infusions.
Six subjects, 2 children and 4 adults, withdrew from the trial during the efficacy treatment period with HYQVIA due to mild to moderate adverse reactions. One child withdrew due to local pain and one due to fever, vomiting, and headaches. Of the four adults, two withdrew due to local pain and swelling, one had moderate swelling that transiently extended from the abdominal infusion site to the genitalia, and one had back injury.
Antibodies binding to rHuPH20: A total of 15 out of 83 subjects who were treated with HYQVIA developed an antibody capable of binding to recombinant human hyaluronidase in the clinical trials. These antibodies were not capable of neutralizing recombinant human hyaluronidase.
In the clinical trial, no temporal association between adverse reactions and the presence of antibodies capable of binding to the Recombinant Human Hyaluronidase of HYQVIA could be demonstrated. There was no increase in incidence or severity of adverse reactions in subjects who developed antibodies to Recombinant Human Hyaluronidase of HYQVIA. In all subjects, antibody titers decreased despite continued treatment.
The effect of exposure to antibodies capable of binding to Recombinant Human Hyaluronidase of HYQVIA for periods longer than this clinical trial has not been eva luated.
The local adverse reactions are listed by frequency in Table 5. Mild swelling around the infusion site was present in most infusions due to the large volumes infused, but in general was not considered to be an adverse reaction unless it caused discomfort. Among the 234 local adverse reactions, three were severe (infusion site pain, infusion site swelling and infusion site edema that extended from the abdominal infusion site to the genitalia); all were transient and resolved without sequelae. More than 98% of local reactions were either mild (7
