Phase III Double-Blind, Randomized, Placebo-Controlled Study of Human Normal Immunoglobulin for Infection Prophylaxis in Chronic Lymphocytic Leukemia with Secondary Immunodeficiency

The primary objective of this study is to demonstrate the benefit of **Panzyga** administration compared with placebo as primary infection prophylaxis in patients with **chronic lymphocytic leukemia** (CLL) and secondary immunodeficiency (SID) undergoing CLL antineoplastic therapy. This is clinically relevant as it aims to reduce infection rates in this vulnerable patient population, potentially improving their overall health outcomes and quality of life.

The secondary objectives of this study are to compare the following aspects in CLL patients with SID treated with and without primary Panzyga prophylaxis:

• Overall infection rate
• Frequency of prophylaxis with anti-infectives (antibacterials and antivirals)
• Duration of prophylaxis with anti-infectives (antibacterials and antivirals)

The clinical trial involves a total of **58 participants** diagnosed with **chronic lymphocytic leukemia (CLL)** and secondary hypogammaglobulinemia. The study population includes both male and female subjects, aged 18 years and older, who are either treatment-naïve or have relapsed/refractory CLL and are undergoing CLL antineoplastic therapy. Participants were selected based on specific criteria, including a confirmed diagnosis of B-cell CLL according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria and documented hypogammaglobulinemia with IgG levels below 5 g/L. The trial population is considered vulnerable, and all participants provided voluntarily given, fully informed written consent prior to any study-related procedures. Lifestyle factors such as diet and physical activity were not specified in the available data.

The clinical trial is designed as a **double-blind**, randomized, placebo-controlled, prospective Phase III study. The primary objective is to evaluate the efficacy and safety of Panzyga in primary infection prophylaxis for patients with **chronic lymphocytic leukemia** (CLL) and secondary hypogammaglobulinemia. The trial aims to demonstrate the benefit of Panzyga administration compared to placebo in CLL patients undergoing antineoplastic therapy. The study is expected to run from July 17, 2020, to March 3, 2025, with a maximum treatment period of 48 weeks for each participant.

Participants will be required to attend several study visits throughout the trial. The initial visit will be a screening visit to confirm eligibility based on criteria such as a diagnosis of B-cell CLL, hypogammaglobulinemia, and age of 18 years or older. Following the screening, eligible participants will be randomized to receive either Panzyga or a placebo. Subsequent visits will include regular follow-up assessments to monitor the occurrence of major infections, overall infection rates, and the frequency and duration of prophylaxis with anti-infectives. The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted to evaluate the primary and secondary endpoints.

Participant involvement is expected to last up to 48 weeks, depending on individual treatment response and adherence to the study protocol. Conditions that may lead to early termination from the study include the occurrence of adverse events, withdrawal of consent, or any protocol violations that compromise the integrity of the trial. The study will adhere to rigorous ethical standards, ensuring that all procedures are conducted with the utmost care and scientific accuracy.

The clinical trial involves the administration of **Panzyga**, a **human normal immunoglobulin** solution for infusion, as the experimental medication. Panzyga is manufactured by Octapharma Pharmazeutika ProduktionsgesmbH and is authorized under the marketing authorization number 236803. The pharmaceutical form is a solution for infusion, and it is administered intravenously. The dosage is calculated based on the participant's body weight, with a maximum daily dose of 4 milliliters per kilogram and a total maximum dose of 52 milliliters per kilogram over the treatment period. The maximum treatment period is 48 days. The primary objective of the study is to evaluate the efficacy and safety of Panzyga as a primary infection prophylaxis in patients with chronic lymphocytic leukemia (CLL) who have secondary immunodeficiency (SID) and are undergoing CLL antineoplastic therapy.

In addition to the experimental treatment, the study includes the use of a placebo, which is an isotonic sodium chloride solution, known as **Isotone Kochsalz-Lösung 0,9 % Braun Infusionslösung**. This solution is produced by B.Braun Melsungen AG and is also administered as a solution for injection/infusion. The placebo is administered via intravenous infusion, with the same dosing schedule as the experimental medication, ensuring blinding and maintaining the study's double-blind design. The sodium chloride solution serves as a comparator to assess the true efficacy of Panzyga in preventing infections in the study population. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

The efficacy of Panzyga in the clinical trial will be assessed through a series of predefined endpoints. The primary endpoint focuses on the occurrence of at least one major infection in patients with Chronic Lymphocytic Leukemia (CLL) receiving Panzyga as primary infection prophylaxis compared to those without it. This endpoint is crucial in demonstrating the benefit of Panzyga administration in reducing infection rates among CLL patients with secondary immunodeficiency undergoing antineoplastic therapy.

Secondary endpoints include the overall infection rate, which accounts for all infections, and the frequency and duration of prophylaxis with anti-infectives, such as antibacterials and antivirals. These parameters will provide a comprehensive evaluation of Panzyga's efficacy in infection prevention. The study is designed as a double-blind, randomized, placebo-controlled, prospective Phase III trial, ensuring rigorous assessment of the treatment's impact.