ecome familiar with the large volumes required for a full 3- or 4-week treatment. Subsequently, subjects continued the 3- or 4-week dosing for the remainder of the trial. After 3 doses at the full volume, a serum IgG trough level was obtained for all subjects, and used to individually adapt the subcutaneous dose of HYQVIA to compensate for individual variation from the mean value of 108% [see Pharmacokinetics (12.3)and Dosage and Administration (2.1)]. All subjects who completed the trial received a minimum of 12 infusions at this individually adapted dose. The period after the ramp-up was considered the efficacy period and used for safety and efficacy analyses.
Outcome measures included the rate of infections, adverse reactions, tolerability of the infusions of HYQVIA, number of infusion sites per month, and infusion rate. Eighty-nine subjects were enrolled, 87 treated intravenously and 83 treated with HYQVIA. The majority were Caucasian (79/87, 90.8%). Median age was 35.0 years (range 4 to 78 years). Forty-four of the subjects were naïve to subcutaneous treatment. Median serum IgG trough levels for the 6 months before enrollment were 1033.5 mg/dL (range: 405 to 3200 mg/dL) in subcutaneous-experienced subjects and 1000 mg/dL (range: 636 to 3200) in the subcutaneous-naïve subjects.
The 83 subjects received a total of 1359 infusions of HYQVIA during the entire trial. Of these, 1129 were administered after the ramp-up when the subjects were on a consistent interval of 3 or 4 weeks, which was predetermined to be the efficacy period for data analysis.
Median duration of treatment in the IGIV period was 91 days (range 84 to 122 days). Median duration of HYQVIA treatment during the dose ramp up period was 42 days (range 20 to 49), and during the efficacy period was 366 days (range 42 to 507 days). None of the subjects withdrew due to a severe or serious local or systemic adverse reaction [see Clinical Trial Experience (6.1)].
There were two acute serious bacterial infections (ASBI); both episodes of pneumonia treated as outpatients with oral antibiotics, during the 12-month efficacy period and one additional pneumonia that required hospitalization during the ramp-up. Based on this, the annualized rate of ASBI while treated with HYQVIA was 0.025, with an upper 99% confidence limit of 0.046, which is significantly less than (p < 0.0001) the rate of one infection per year10.
The overall rates of infections throughout both the efficacy and extension trials are shown in Table 8. The secondary endpoints eva luated in the efficacy trial were the annual rate of all infections and other efficacy measures.
Table 8 Summary of Infections and Other Secondary Efficacy Endpoints Annual Rate
Parameter
Mean
95% CI
Infections per patient per year
(Efficacy Trial)
2.97
2.51 to 3.47
Infections per patient per year
(Efficacy and Extension Trials)
2.99
2.60 to 3.92
Days off school/work
3.41
2.44 to 4.5
Days on antibiotics
20.58
15.71 to 26.3
Unscheduled physician visits for
infections
4.87
3.9 to 5.97
Days in hospital due to infection
0.0
0.0 to 0.12
An objective of the trial was to achieve the same number or fewer infusions with HyQvia per
month as with intravenous administration and significantly fewer t
