Phase 3 Randomized Trial of Human Normal Immunoglobulin to Prevent Infections in IgG‑deficient Patients with Autoimmune/Rheumatic Disease on B‑cell Depletion Therapy

The primary objective is to demonstrate the efficacy of Panzyga versus placebo for preventing major infection in patients with hypogammaglobulinemia and autoimmune or rheumatic diseases who are receiving B-cell depletion therapy; achieving this would reduce infection‑related morbidity and support continued disease‑modifying treatment.

Secondary objectives:

• Further evaluate the efficacy of Panzyga versus placebo for extending the period without a major infection.
• Assess the safety of Panzyga versus placebo when used for infection prophylaxis in this patient population.

The trial enrolled 195 adult patients of both sexes who were ≥18 years old and had a diagnosed autoimmune or rheumatic disorder; eligible conditions included multiple sclerosis, rheumatoid arthritis, vasculitis, systemic lupus erythematosus, Sjögren’s syndrome, idiopathic inflammatory myopathies, mixed connective‑tissue disease, myasthenia gravis, autoimmune encephalitis, CIDP, neuromyelitis optica spectrum disorder, and other similar diseases approved by the Medical Monitor. All participants exhibited hypogammaglobulinemia (IgG < 5 g/L) and had received their most recent dose of B‑cell depletion therapy within three months prior to screening, with the intention to continue such therapy during the study. The population included individuals classified as vulnerable, and both male and female participants were required to use an effective contraception method during the study and for 30 days thereafter. Enrollment was based on voluntary written informed consent and compliance with protocol requirements, and the investigational product, Panzyga, was compared with placebo for the prevention of major infections in this high‑risk cohort.

The study is a Phase 3, multicenter, hypogammaglobulinemia trial employing a randomized, double‑blind, placebo‑controlled design in which participants receive either Panzyga 100 mg/ml solution (human normal immunoglobulin, 4 ml/kg IV) or an identical‑appearing isotonic saline placebo (4 ml/kg IV). Eligible adults (≥18 years) with a diagnosed autoimmune or rheumatic condition, who have received their most recent B‑cell depletion therapy within three months and meet the IgG < 5 g/L criterion, are screened, consented, and randomized in a 1:1 ratio. The overall trial spans approximately three years (May 2026 to May 2029). After the screening visit, a baseline visit includes randomization and the first infusion; subsequent follow‑up visits are scheduled at regular intervals to record major infection events, assess safety parameters, and perform laboratory and physical examinations. The final assessment occurs at the end‑of‑study visit, concluding each participant’s involvement from screening through the last scheduled follow‑up. Participants may be withdrawn early for reasons such as serious adverse events, protocol non‑compliance, loss to follow‑up, or voluntary discontinuation, at which point data collected up to the point of termination are retained for analysis.

The investigational product is Panzyga, a 100 mg/ml solution for infusion containing human normal immunoglobulin. It is administered intravenously at a dose of 4 ml per kilogram of body weight. The infusion is performed according to the protocol‑defined schedule and uses a standard infusion set for the solution for infusion dosage form.

The comparator is a placebo consisting of Isotone Kochsalz‑Lösung 0.9 % Braun Infusionslösung, which contains sodium chloride. The placebo is also delivered intravenously at a dose of 4 ml per kilogram of body weight, using the same infusion procedure as the active product to maintain blinding.

Both study treatments are administered as scheduled infusions throughout the trial period. Dosing intervals are defined in the study protocol and are identical for the active and placebo arms. Participant compliance is monitored by recording infusion start and end times, verifying administered volume against the calculated dose, and documenting any interruptions or deviations in the case report form. Serum immunoglobulin levels are assessed at predefined visits to support adherence monitoring and to evaluate pharmacodynamic effects.

Efficacy will be evaluated primarily by the proportion of participants experiencing at least one major infection or death during the study period. Each infection will be recorded continuously, classified by type and severity, and the time to resolution will be documented. An Independent Adjudication Committee will review all potential infections to confirm eligibility for the primary analysis, and each patient will be counted only once for this endpoint.

Secondary efficacy assessment includes the time from randomization to the first occurrence of a major infection or death, as determined by the same adjudication process. These time-to-event data will be analyzed using appropriate survival analysis methods.