en-label, single-arm, multicenter trial assessed the efficacy, safety, and pharmacokinetics of ASCENIV inadult and pediatric subjects with PI. Study subjects were receiving regular IGIV replacement therapy, with a stable dosebetween 300 and 800 mg/kg for at least 3 months prior to participation in this trial. Subjects received an ASCENIV infusionadministered every 3 or 4 weeks (both the dose and schedule depending on their prior therapy) for 12 months.
A total of 59 subjects were enrolled into the trial, 28 men and 31 women with a mean age of 42 years; 93% were Caucasian, 5%
were Hispanic and 2% African American. Forty-eight subjects were adults (81%) between 17 and 74 years of age. There were11 pediatric subjects (see Pediatric Use [8.4]), and 11 subjects (18.6%) ≥65 years of age. The oldest subject was 74 years ofage. The youngest subject was 3 years of age.
There were 19 subjects with a 3-week cycle and 40 subjects with a 4-week cycle. There were 45 subjects (76%) withcommon variable immunodeficiency (CVID) as their primary diagnosis, followed by X-linked Agammaglobulinemia (10%),Antibody Deficiencies and ‘Other’ (7% each). The modified intent-to-treat (mITT) population included 59 subjects and wasused for efficacy analysis.
The study assessed the efficacy of ASCENIV in preventing serious bacterial infections (SBIs), defined as a rate of <1.0 casesof bacterial pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, visceral abscess, and bacterial meningitis perperson-year. Secondary efficacy parameters included time to first SBI and time to first infection of any kind/seriousness, dayson antibiotics (excluding prophylaxis), days off school/work due to infections, all confirmed infections of any kind or seriousness,and hospitalizations due to infection.
During the 12-month study period, zero (0) serious acute bacterial infections occurred. Thus, the mean event rate of serious,acute, bacterial infections per year was 0.0 (with an upper 1-sided 99% confidence interval of <1.0 per subject year, which metthe study’s primary efficacy endpoint).
Thirty-nine percent (39%) of subjects had days off work, school or daycare due to an infection. Of the infections reported, 1resulted in hospitalization as a post-op local wound infection from elective surgery (see Table 6). The incidence and severity ofinfections in adolescents were similar to those in adult subjects.
Table 6: Summary of Efficacy Results in Subjects with PI
Number of Subjects (mITT Population) 59
Total Number of person-yearsa 55.9
Infections
Number of confirmed serious acute bacterial infectionsb 0
Rate of SBIs (SBIs/total person-years) 0.0
Rate of Infections (Infections/total person-years) a 3.4
Antibiotic use due to infectionc
Number of subjects (%) 37 (63%)
Days per subject per year 32.9
Days off school/daycare/work due to infection
Number of persons with days off of school, daycare or work due to infections 23 (39%)
Total days 93
Days per subject per year 1.7
Unscheduled Medical Visits due to infection
Number of persons with unscheduled medical visits due to infections (%) 24 (41%)
Total visits 54
Visits per subject per year 0.97
Hospitalization due to infection
Number of subjects (%) 1 (1.7%)
Number of Days 5
Hospitalizations per subject per year 0.02
SBI = serious bacterial infections. a
Person-years: Person-time in years with 2 decimals = (the Final Clinical Visit Date - the Day 0 date+1) / 365.25, |
