A prospective, open-label, single-arm, multicenter trial assessed the efficacy, safety, and pharmacokinetics of BIVIGAM in adult and pediatric subjects with PI. Study subjects were receiving regular IGIV replacement therapy, with a stable dose between 300 and 800 mg/kg for at least 3 months prior to participation. Subjects received a BIVIGAM infusion administered every 3 or 4 weeks (both the dose and schedule depending on their prior therapy) for approximately 1 year.

A total of 63 subjects were enrolled in the trial, 31 men and 32 women with a mean age of 41 years. Forty-four subjects were adults (70%) between 18 and 64 years of age. There were 9 pediatric subjects ( see Pediatric Use [8.4]), and 9 elderly subjects (14%, ≥65 years of age). The oldest subject was 75 years of age. 

There were 17 subjects with a 3-week cycle and 46 subjects with a 4-week cycle. There were 51 subjects (81%) with common variable immunodeficiency as their primary diagnosis, followed by X-linked agammaglobulinemia and ‘Other’ (9.5% each). The intent to treat (ITT) population included 58 subjects and was used for efficacy analysis.

The primary endpoint of the study was to assess the efficacy of BIVIGAM in preventing serious bacterial infections (SBIs) defined as rate of <1.0 cases of bacterial pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, visceral abscess, and bacterial meningitis per person-year. Secondary efficacy parameters included time to first SBI and time to first infection of any kind/seriousness, days on 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, two serious acute bacterial infections occurred in two subjects with an onset date between the first infusion of BIVIGAM and the first follow-up visit, inclusive. Thus, the mean event rate of serious, acute, bacterial infections per year was 0.037 (with an upper 1-sided 99% confidence interval of 0.101, which met the study’s primary efficacy endpoint).

The two SBIs were cases of bacterial pneumonia. Thirty-three percent of subjects had days off work or school due to an infection. Of the 197 infections reported, 2 resulted in hospitalization. Results for the pediatric subjects were similar to those for the adult subjects. (see Table 7).

Table 7: Summary of Efficacy Results in Subjects with PI

Pediatric Only Study

A prospective, open-label, single-arm, multi-center study evaluating the safety, efficacy, and PK of BIVIGAM was conducted in 16 pediatric subjects; 3 subjects ≥2 to <6, 5 subjects ≥6 to <12, and 8 subjects ≥12 to ≤16 years, with confirmed and documented clinical diagnosis of PID, including hypogammaglobulinemia or agammaglobulinemia. Of the 16 subjects enrolled, all (100%) were male, and the majority (80%) were white.

Subjects received a BIVIGAM infusion administrated every 3 or 4 weeks (based on the dose and schedule depending on their prior treatment regimen) for approximately 5 months. Average BIVIGAM doses administered (all infusions, both infusion regimens combined, values rounded) ranged from 368 to 1077 mg/kg in the 2 to <6 years age group, from 312 to 693 mg/kg in the 6 to <12 years age group and from 350 to 795 mg/kg in the 12 to 16 years age group.

The efficacy analysis is based on the incidence of acute serious bacterial infections (SBIs). SBIs encompass bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, or visceral abscess. No acute SBIs occurred during the mean observation period of 152 days, yielding a mean number of acute SBI episodes per person-year of 0.0. No other serious infections, or hospitalizations due to infections occurred, and no subjects required IV antibiotics during the study.

Trough Total IgG levels were maintained above 500 mg/dL in all subjects throughout the study. There were no apparent differences in the Total IgG or subclass concentrations before the first and last infusions.