Pharmacokinetic Non‑Inferiority and Safety of Subcutaneous IGSC 20% (Xembify) vs Intravenous IGIV‑C 10% (Gamunex‑C) in Adults with CIDP

The primary objective is to assess whether the subcutaneous immunoglobulin 20% (IGSC 20%) administered at 0.456 g/kg weekly achieves a steady‑state area under the concentration‑time curve (AUC) for total immunoglobulin G that is non‑inferior to the intravenous immunoglobulin 10% (IGIV‑C) given at 1 g/kg every three weeks over a 39‑week period in participants with Chronic inflammatory demyelinating polyradiculoneuropathy. The secondary objective is to evaluate whether weekly IGSC 20% maintains steady‑state mean trough total IgG concentrations comparable to those obtained with IGIV‑C administered every three weeks.

The trial enrolled a total of 20 participants diagnosed with Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Eligible individuals were male or female adults aged 18 years or older, with a body weight of 90 kg or less, and who were clinically stable on intravenous immunoglobulin therapy without recent changes in treatment or relapse for at least 12 weeks prior to screening. All participants were required to provide written informed consent and to be able to adhere to the study protocol for the duration of the trial. The population comprised patients meeting the 2021 European Academy of Neurology/Peripheral Nerve Society diagnostic criteria for typical CIDP or a CIDP variant, with an IGIV dose requirement of 0.3–1.0 g/kg every three weeks (20–90 g per dose). No specific lifestyle restrictions regarding diet, physical activity, or habits were stipulated in the inclusion criteria. Vulnerable individuals were not excluded, and both genders were represented in the study cohort.

The study is an open‑label, multicenter Phase III trial evaluating the pharmacokinetics and safety of subcutaneous Xembify (0.456 g/kg weekly) versus intravenous Gamunex‑C (1 g/kg every 3 weeks) in participants with Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP). The protocol comprises a screening visit to confirm eligibility and obtain informed consent, followed by a baseline visit that initiates the IV comparator phase. Participants receive the IV dose for one dosing interval (3 weeks) to establish steady‑state IgG exposure, after which they transition to the weekly SC dosing phase for a total study period of up to 39 weeks. Study visits are scheduled at each dosing point (weekly during the SC phase and every 3 weeks during the IV phase) to collect blood samples for AUC assessment, monitor trough IgG levels, and evaluate safety. An end‑of‑study visit concludes the trial and includes final pharmacokinetic sampling and safety assessments. Participant involvement therefore spans approximately 39 weeks, with regular clinic assessments throughout. Early termination may occur if a participant experiences a serious adverse event related to study medication, violates key protocol requirements, withdraws consent, or is otherwise unable to continue the assigned treatment regimen.

The investigational product, Xembify 200 mg/ml solution for subcutaneous injection, contains human normal immunoglobulin as the active substance. The administered dose is 0.456 g/kg body weight, delivered by subcutaneous injection once weekly (QW) throughout the study period of up to 39 weeks. The formulation is a sterile aqueous solution intended for single‑use administration via a pre‑filled syringe or an infusion set.

The comparator, Gamunex® 10% (100 mg/ml) solution for infusion, also comprises human normal immunoglobulin. Participants receive a dose of 1.0 g/kg body weight administered as an intravenous infusion every three weeks (Q3W) for the same duration. The product is supplied in a sterile vial for preparation and infusion according to standard intravenous immunoglobulin protocols.

Both treatment arms follow a predefined dosing schedule with the first dose administered on Day 1. Subsequent doses are given according to the assigned interval (weekly for Xembify, every 21 days for Gamunex). Dosing calculations are based on the participant’s most recent body weight measurement. Compliance is monitored by recording each administration in the electronic case report form, confirming infusion or injection completion, and documenting any deviations or missed doses. Safety laboratory assessments and pharmacokinetic blood sampling are performed at scheduled visits to evaluate steady‑state IgG exposure.

The study enrols individuals diagnosed with Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) who meet all eligibility criteria. All investigational and comparator products are stored, handled, and administered in accordance with the respective product labeling and Good Clinical Practice requirements.

The efficacy assessment is based on pharmacokinetic endpoints that quantify exposure to total immunoglobulin G (IgG). Primary endpoints include the AUC of total IgG over the dosing interval during the intravenous (IV) phase (steady‑state AUC(0–21 days)) and during the subcutaneous (SC) phase (steady‑state AUC(0–7 days)). A secondary endpoint is the steady-state mean trough (pre‑dose) concentration of total IgG following IV administration of IGIV‑C 10 % every three weeks or SC administration of IGSC 20 % weekly.

Serum IgG concentrations will be measured using a validated immunoassay. In the IV phase, blood samples will be collected before the dose and on days 1, 3, 7, 14, and 21 of each 3‑week interval; in the SC phase, samples will be collected before the dose and on days 1, 3, 5, and 7 of each weekly interval. The collected concentrations will be used to calculate AUC for each participant by the trapezoidal method, and mean trough levels will be derived from pre‑dose samples at steady state. Comparative analysis will employ appropriate statistical models to evaluate non‑inferiority of the SC regimen relative to the IV regimen.