CytoGam for CMV Infection or Disease in Solid Organ Transplant Recipients

CytoGam® as Adjuvant Therapy to Prevent or Attenuate Human Cytomegalovirus (CMV) Infection and Disease in Solid Organ Transplant Recipients

Cytomegalovirus (CMV) is a significant opportunistic pathogen and a major cause of morbidity and mortality in solid organ transplant recipients. CytoGam - Cytomegalovirus Immune Globulin Intravenous (CMV-IGIV), is an immunoglobulin G containing a standardized amount of antibody against CMV. CytoGam is obtained from pooled adult human plasma that has been selected for high anti-CMV titers. This study will evaluate if administration of CytoGam to organ transplant recipients with CMV infection, along with standard of care antiviral medication, leads to faster clearance of CMV from the blood, prevents the development of antiviral resistance, and decreases the rate of recurrence of CMV infection.

Interventional, open-label, single center, pilot study to test the effect of CytoGam on CMV viremia clearance in organ transplant recipients with high CMV viral load and in CMV D+/R- lung and liver transplant recipients with primary CMV infection.

CMV D+/R- lung transplant recipients who develop any level of CMV DNAemia after discontinuation of valganciclovir prophylaxis and who have not yet received antiviral treatment for greater than 14 days will receive one dose of CytoGam. The choice and duration of antiviral therapy will be at the discretion of the treating physician. Patients will be followed until 2 weekly negative CMV PCRs, discontinuation of antiviral, or 1 year from CytoGam infusion, whichever is longer.

CMV D+/R- liver transplant recipients on pre-emptive therapy who develop any level of detectable CMV DNAemia and who have not yet received antiviral treatment for greater than 14 days will receive one dose of CytoGam. The choice and duration of antiviral therapy will be at the discretion of the treating physician. Patients will be followed until 2 weekly negative CMV PCRs, discontinuation of antiviral, or 1 year from CytoGam infusion, whichever is longer.

Recipients of any solid organ transplant who have CMV DNAemia ≥ 50,000 IU/ml, with or without CMV disease, and who have not yet received antiviral therapy for greater than 14 days will receive one dose of CytoGam. The choice and duration of antiviral therapy will be at the discretion of the treating physician. Patients will be followed until 2 weekly negative CMV PCRs, discontinuation of antiviral, or 1 year from CytoGam infusion, whichever is longer.

Inclusion Criteria - all study arms:

• Written informed consent obtained from the subject before any trial-related procedures are performed
• >= 18 years and <= 75 years of age at time of consent
• Able to perform routine blood testing (standard care for transplant recipients)
• Understands and can read English

Inclusion criteria - high viral load arm:

• Recipient of an organ transplant (lung, heart, liver, kidney, pancreas, intestine alone or in combination) and on immunosuppression
• CMV DNAemia ≥ 50,000 IU/ml in the first 2 weeks of CMV antiviral treatment with CMV antiviral dose appropriately adjusted for renal function

Inclusion criteria - CMV primary infection after liver transplantation arm:

- Liver transplant recipients who are CMV IgG negative and received a CMV IgG positive donor (CMV D+/R-) with a primary CMV infection, defined as detected CMV DNAemia, including detected but below the limit of quantitation

Inclusion criteria - CMV primary infection after lung transplantation arm:

- Lung transplant recipients who are CMV D+/R- with a primary CMV infection after discontinuation of CMV antiviral prophylaxis, defined as detected CMV DNAemia, including detected but below the limit of quantitation

Exclusion Criteria:

• History of hypersensitivity to or a prior severe reaction associated with the administration of CytoGam or other human immunoglobulin preparation
• Receipt of effective CMV antiviral treatment, appropriately adjusted for renal function, for greater than or equal to 14 days prior to enrollment
• Selective IgA deficiency, as they may produce antibodies against immunoglobulin A (IgA), leading to potential anaphylactic reactions upon administration of blood products containing IgA, including CMV immunoglobulin (e.g. CytoGam or similar)
• Prior history of hematopoietic cell transplant
• Pregnancy
• Participation in another interventional clinical trial at time of consent or within 30 days prior to study consent
• Any condition which, in the judgement of the investigator, would make administration of CytoGam unsafe