Purpose The purpose of this phase 3 study was to evaluate the efficacy, pharmacokinetics (PK), and safety of Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%) in patients with primary immunodeficiency (PI). Methods Immunoglobulin treatment-experienced subjects with PI received 52 weeks of IGSC 20% given weekly at the same dose as the subject’s previous IgG regimen (DAF 1:1); the minimum dose was 100 mg/kg/week. The primary endpoint was serious bacterial infections (SBIs [null vs alternative hypothesis: SBI rate per person per year ≥ 1 vs < 1]). IgG subclasses and specific pathogen antibody levels were also measured. Results Sixty-one subjects (19 children [≤ 12 years], 10 adolescents [> 12–16 years], and 32 adults) were enrolled. The rate of SBIs per person per year was 0.017. The 1-sided 99% upper confidence limit was 0.036 (< 1), and the null hypothesis was rejected. The rate of hospitalization due to infection per person per year was 0.017 (2-sided 95% confidence interval: 0.008–0.033) overall. The mean trough total IgG concentrations were comparable to the previous IgG replacement regimen. The average of the individual mean trough ratios (IGSC 20%:previous regimen) was 1.078 (range: 0.83–1.54). The average steady-state mean trough IgG concentrations were 947.64 and 891.37 mg/dL, respectively. Seven subjects had serious treatment-emergent adverse events (TEAEs); none was drug-related. The rate of all TEAEs, including local infusion site reactions, during 3045 IGSC 20% infusions was 0.135. Most TEAEs were mild or moderate. Conclusions IGSC 20% demonstrated efficacy and good safety and tolerability in subjects with PI.

Immune globulin subcutaneous, human – klhw 20% solution (IGSC-C 20%) is a new treatment for patients with PI. The primary objective determined whether the pharmacokinetics (PK) of IGSC-C 20% is noninferior to intravenous (IV) immune globulin injection (human),10% caprylate/chromatography purified (IGIV-C 10%). This study included participants, aged 2–72 years with PI (n=53). Participants received IGIV-C 10% during the Run-in Phase (n=44) prior to IV PK profiling or entered the IV Phase directly (n=9), then switched to weekly infusions of IGSC-C 20% (n=49) for approximately 24 weeks at a dose adjustment factor (DAF) of 1.37. The primary (PK IgG) and exploratory (infection rates and pathogen antibody titers) endpoints were assessed. Steady state IgG trough concentration was 1.333-fold higher with IGSC-C 20% (∼1245 mg/dL) than IGIV-C 10% (∼957 mg/dL). The geometric least-squares means ratio of the area-under-the-curve for IGSC-C 20% (n=39) vs IGIV-C 10% (n=49) was 104% (90% CI: 100%–107%). IGIV-C 10% rose rapidly to 2075 (range: 1350–3000) mg/dL IgG followed by a decline; IGSC-C 20% postinfusion remained stable between 1263 mg/dL and 1358 mg/dL through 7 days. The rates of serious bacterial infections per subject-year was 0.049 (95% CI: 0.020-0.098; upper 99% CL: 0.110) with IGSC-C 20% and 0.120 (0.051-0.232; 0.259) with IGIV-C 10%. Infection rates and trough pathogen antibody titers were comparable between treatments. IGSC-C 20% (at DAF of 1.37) provided noninferior and bioequivalent IgG exposure to IGIV-C 10%, with 33% higher mean IgG trough values, and less fluctuations in IgG concentrations.

This trial assessed the safety and tolerability of IGSC-C 20% and intravenous immune globulin infusion (human),10% caprylate/chromatography purified (IGIV-C 10%) in participants with PI. There were 3 phases: Run-in (IGIV-C 10%, n=44), IV (IGIV-C 10%, n=52 [9 entered without Run-in]), and SC (weekly IGSC-C 20%, dose adjustment factor of 1.37, n=49). Safety analyses were performed. Local infusion site reactions (ISRs) were considered adverse events (AEs) when signs/symptoms led to infusion interruption/discontinuation, required concomitant medication, or impacted the general condition of the participants. Of the 261 IGIV-C 10% and 1053 IGSC-C 20% infusions, 99.7% completed without interruption. Most IGSC-C 20% infusions used 2 (30.5%) or 4 (56.2%) infusion sites. During the Run-in+IV phases, 33 participants reported 79 AEs. Forty-one participants reported 141 AEs during the SC phase. Most (>96%) AEs were mild to moderate in severity. One participant reported 2 serious AEs (SAEs) in the Run-in+IV phases and 2 in the SC phase reported 4 SAEs; all unrelated to study drug. Rates of potentially related AEs (PRAEs) per infusion were 0.050 in Run-in+IV and 0.058 in SC phases. Headache was the most frequent PRAEs in the Run-in+IV phases (3.8%, 0.008 event/infusion); whereas, 1 participant (2.0%, 0.001 event/infusion) in SC Phase experienced headache. The majority (98.3%) of PRAEs in the SC phase were mild or moderate in severity, primarily local ISRs. There were no treatment-emergent fatigue or nausea, thromboembolic AEs, or death during this study. IGSC-C 20% is well tolerated and has a safety profile similar to IGIV-C 10% in this study.

Objective: New formulations and applications of hemostatic adjuncts such as fibrin sealant (FS) to support local hemostasis and sutures continue to be developed. In a pivotal, confirmatory, controlled, prospective, single-blinded, randomized, multicenter phase III clinical trial, the efficacy and safety of FS Grifols during vascular surgeries were evaluated. Methods: Patients undergoing a nonemergency, open, peripheral vascular surgical procedure with moderate arterial bleeding were recruited. In an initial preliminary part of the study, all patients were treated with FS Grifols. In a subsequent primary part, patients were randomized (2:1) to FS Grifols or manual compression (MC). The primary efficacy end point was the proportion of the primary part patients achieving hemostasis by 4 minutes after the start of treatment. Cumulative proportion and time to hemostasis were secondary efficacy end points. Safety end points (in pooled preliminary and primary parts) included adverse events (AEs), vital signs, physical assessments, clinical laboratory tests, viral markers, and immunogenicity. Results: The primary efficacy end point was met by 76.1% of patients (83/109) for the FS Grifols group versus 22.8% of patients (13/57) for the MC group (P < .001). The cumulative proportion of patients at 5, 7, and 10 minutes was 80.7%, 84.4%, and 88.1%, respectively, in the FS Grifols treatment group, and 28.1%, 35.1%, and 45.6% in the MC treatment group (P < .001). The median time to hemostasis was shorter in the FS Grifols group (4 minutes vs >= 10 minutes in the MC group; P < .001). The nature of AEs reported were those expected in the study patient profile. The percentage of patients experiencing treatment-emergent AEs were similar in both the FS Grifols (pooled n = 59 + 109) and MC groups (81.0% and 77.2%, respectively), most recurrent being procedural pain (34.5% and 36.8%, respectively) and pyrexia (11.3% and 10.5%, respectively). Conclusions: FS Grifols was superior in efficacy and similar in safety to MC as an adjunct local hemostatic agent in patients undergoing open vascular surgeries.