Double-blind, Randomized, Placebo-controlled, Prospective Phase III Study Evaluating Efficacy and Safety of Panzyga in Primary Infection Prophylaxis in Patients With Chronic Lymphocytic Leukemia (PRO-SID Study)

Study Overview
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Brief Summary
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Study Evaluating Efficacy and Safety of Panzyga in Primary Infection Prophylaxis in Patients with Chronic Lymphocytic Leukemia

Official Title
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Double-blind, Randomized, Placebo-controlled, Prospective Phase III Study Evaluating Efficacy and Safety of Panzyga in Primary Infection Prophylaxis in Patients With Chronic Lymphocytic Leukemia (PRO-SID Study)

Conditions
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Chronic Lymphocytic Leukemia, Hypogammaglobulinemia

Intervention / Treatment
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* Biological: Panzyga
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment-naïve or relapsed/refractory CLL patients undergoing CLL antineoplastic treatment. Diagnosis of B-cell CLL established according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria and documented within medical records. Hypogammaglobulinemia (IgG levels <5 g/L) as confirmed by the Central Laboratory. ≥18 years of age. Voluntarily given, fully informed written and signed consent obtained before any study-related procedures are conducted. Exclusion Criteria: IgG treatment within 3 months prior to Screening. Antibiotic prophylaxis and/or treatment within 7 days prior to Baseline (with the exception of trimethoprim-sulfamethoxazole [TMP/SMX], diaminodiphenyl sulfone [dapsone] and pentamidine inhalation). Current major infection or >1 major infection in the previous 6 months before Baseline. History of anaphylaxis or severe systemic response to immunoglobulin, blood or plasma-derived products or any Panzyga component. History of a non-CLL malignancy or other medical condition with life-expectancy of less than two years. Severe liver disease, with signs of ascites and/or hepatic encephalopathy. Severe kidney disease (as defined by estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2). Body weight >140 kg. Eastern Cooperative Oncology Group (ECOG) performance score of >2 (Appendix 1). Female patients of childbearing potential unwilling to use a protocol-required method of contraception (as per protocol section 7.3.9 b) from the Screening Visit throughout the study treatment period and for 30 days following the last dose of study drug. Human immunodeficiency virus (HIV) infection at Screening (defined for the study as positive HIV antibody test). Patients found to be chronic carriers of hepatitis B virus (HBV), defined by positive surface antigen (HBsAg), positive Hepatitis B core antibodies (HBcAb) and/or low HBV titers, who will not receive targeted antiviral therapy while undergoing CLL therapy, and patients with active HBV, defined as high HBV titers. Uncontrolled hepatitis C infection at Screening (defined for the study as positive hepatitis virus C [HCV] polymerase chain reaction [PCR]). Pregnant and lactating women. Subjects with a history of thromboembolic events (TEE) such as deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, transient ischemic attack, peripheral artery disease (Fontaine IV) within 6 months before Baseline. Planned or ongoing immunosuppressive treatment (other than for CLL or corticosteroids) or other forbidden medication during the entire study duration after study enrollment. Participation in another interventional clinical trial that is either blinded or involves an investigational (not approved) product within 3 months before Baseline or during the course of the clinical study. Participation in observational clinical trials or open-label trials involving an approved product may be permitted after consultation with the medical monitor. Known IgA deficiency with antibodies to IgA. Known blood hyperviscosity, or other hypercoagulable states. Patients unable or unwilling to understand or comply with the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panzyga<br> | Biological: Panzyga<br>* Panzyga is a 10% IVIG produced from a pool of human fresh frozen plasma donations<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of major infections | Major infection for this trial is defined as: Bacterial and/or viral infections resulting in death Bacterial and/or viral infections, which are microbiologically documented (MDI) or clinically documented (CDI) requiring treatment with anti-infectives; upper respiratory tract infections, bronchitis, lower urinary tract infections, localized skin infections and stomatitis (MDI or CDI) are considered major only if they require treatment with antiinfectives AND hospitalization or hospitalization prolongation. Fever of unknown origin (FUO) requiring hospitalization or hospitalization prolongation | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall infection rate | Infection rate for all infections | 52 weeks | 
| Frequency of prophylaxis with anti-infectives | Inclusive of antibacterials and antivirals | 52 weeks | 
| Duration of prophylaxis with anti-infectives | Inclusive of antibacterials and antivirals | 52 weeks |