The AE was considered at least possibly related to study medication; it resolved without sequelae after 13?days. variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA) are main immunodeficiency (PID) disorders that predispose patients to recurrent infections and chronic lung disease [1C6]. Patients require immunoglobulin replacement therapy, which can be administered intravenously (IVIG) or subcutaneously (SCIG) [7C14]. Subcutaneous administration produces stable serum IgG levels and is associated with fewer systemic adverse events (AEs). Although head-to-head studies have not been performed, retrospective analyses and two crossover trials have demonstrated a lower incidence of systemic AEs in patients receiving SCIG compared to IVIG [15C23]. Recently, SCIG has gained acknowledgement due to its suitability Microcystin-LR for self-infusion and home therapy, both offering greater flexibility to patients [20]. IgPro20 is usually a new 20% liquid SCIG product with high purity (98% IgG) manufactured from human plasma of more than 15,000 donors by a process identical to that of IgPro10 (Privigen?), which has an established demanding pathogen security profile [24]. The high IgG concentration in IgPro20 allows for infusion of lower volumes compared to currently available 16% IgG products administered at equivalent dose. Tmem26 This potentially solves an existing problem with SCIG therapy for some patients, namely, the number of infusion sites or doses required to provide adequate IgG replacement. Despite high protein concentration, IgPro20 has outstanding answer properties and can be administered at relatively high infusion ratesCa substantial technical achievement. Formulation with L-proline and Polysorbate 80 allows storage of IgPro20 for up to 24?months at 25C without any loss of functional activity (Maeder et al., in preparation). We statement results on local tolerability in healthy volunteers from a phase I study, as well as efficacy and tolerability of IgPro20 in patients with PID from a recently completed prospective, open-label, multicenter, single-arm, phase III study (NCT00419341). Methods Phase I Local Tolerability Study in Healthy Subjects Subjects Twenty-eight healthy, male, white subjects aged 18 to 45?years were recruited. Inclusion criteria included a body mass index (BMI) of Microcystin-LR 21C27?kg/m2, no clinically significant medical history, and good health (as determined by a detailed medical history, complete physical examination, electrocardiogram, and clinical laboratory screening). Subjects were excluded in case of evidence of any clinically relevant pathology that could interfere with the study results or put the subjects safety at risk. This study was conducted in accordance with the Microcystin-LR International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines, and the Declaration of Helsinki (version of 1996). The study protocol and all other study documents were approved by the relevant Independent Ethics Committees. Subjects signed an informed consent prior to entering the study. Study Design This was a single-center, randomized, four-way crossover, assessment-blinded study. The study objective was to compare the local tolerability of IgPro16 and IgPro20 with Vivaglobin?. IgPro16 and IgPro20 are 16% and 20% liquid human IgG products, respectively, formulated with 28.8?mg/mL (250?mmol/L) of L-proline and 20?mg/L of Polysorbate 80 at pH 4.8; Vivaglobin? is a 16% liquid human IgG formulated with 22.5?mg/mL (300?mmol/L) of glycine at pH 6.4C7.2. Each patient received a single subcutaneous dose of IgPro16 15?mL, IgPro20 15?mL, IgPro20 12?mL, or Vivaglobin 15?mL at a single abdominal site on day 1 at 25?mL/h. The next test samples Microcystin-LR were administered at weekly intervals at different abdominal sites. The primary end point was assessment of local tolerability from the start of infusion to 72?hours after the end of infusion. Local tolerability included pain (assessed by subjects), erythema, edema/induration, itching, and local heat (assessed by a treatment-blinded investigator). Tolerability Assessments Assessments were performed by treatment-blinded investigators after the end of infusions. Erythema and edema were evaluated Microcystin-LR using 5-point scales ranging from none (score 0) to severe (score 4). Itching and local heat were evaluated using a 4-point scale ranging from none (score 0) to severe (score 3). Pain was evaluated.