Strategic Help With Immunoglobulin to Enhance Protect Against Late Disease (CMV)

NCT06958796 | Recruiting Phase 4 FDA Drug

• 1 other identifier: 2024P003592
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

This study is being done to find out if administering CytoGam® after the end of standardly prescribed preventive antiviral treatment can help transplant recipients with a high risk for developing late CMV disease after a liver and/or kidney transplant.

Conditions

Cytomegalovirus; Organ Transplant; Kidney Transplant; Complications; Liver Transplant Complications; Simultaneous Liver-Kidney Transplantation; Complications

Keywords

cytomegalovirus; valganciclovir; organ transplant; immunoglobulin; CMV; High Risk CMV

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Late Clinically Significant CMV Disease

  Comparison between treatment groups of number of participants with a blood CMV viral load \>1000 IU/ml at any point during the treatment phase through end of study

  Treatment Phase (Day 0) through End of Study (Day 168)

• Number of Participants with Adverse Events Related to CMV

  Congregate data of all Adverse Events (including Serious Adverse Events) will be compared between treatment arms. The number and percent of CMV related AEs will be summarized by: Organ system impacted Relationship to CMV Severity Deaths Those leading to: 1. Initiation of CMV treatment 2. Hospitalization due to CMV

  Events starting after or increasing in severity following initiation of the Treatment Phase (Day 0) through end of study (Day 168)

Secondary Outcomes (3)

• Peak CMV DNA Levels

  From Enrollment, through the Treatment Phase (Day 0) until the end of study (Day 168)

• Change in CMV DNA Levels Across Study Groups

  From Enrollment, through the Treatment Phase (Day 0) until the end of study (Day 168)

• Time to First Detectable CMV DNAemia

  Treatment Phase (Day 0) through End of Study (Day 168)

Study Arms (2)

Arm A: CytoGam®

EXPERIMENTAL

Participants assigned to receive CytoGam® will receive an infusion once a month for three months at their study site. The infusion will be completed over an average of about 4 hours; these three visits will last about 5 hours. During these study staff will review concomitant medications and adverse events. Participants will be asked to have blood taken at infusion visits and 2 weeks after an infusion visit to check the level of CMV DNA in their blood.

Drug: Cytomegalovirus Immune Globulin Intravenous (Human) monthly for three months

Arm B: Standard of Care

NO INTERVENTION

Participants assigned to Arm B, will be asked to complete a telephone call visit once a month. During these visits, a member of study staff will review concomitant medications and adverse events. Participants will be asked to have their blood taken every two weeks to check the level of CMV DNA.

Interventions

Cytomegalovirus Immune Globulin Intravenous (Human) monthly for three months DRUG

The interventional arm will receive Cytomegalovirus Immune Globulin Intravenous (Human) monthly for three months as (150 mg/kg) for 3 consecutive months (Days 0, 28 and 56 +/- 3 days). The non-interventional arm will not receive any intervention.

Arm A: CytoGam®

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• High risk pretransplant CMV donor seropositive/recipient seronegative (D+R-) kidney, liver, or simultaneous liver-kidney (SLK) transplant recipients
• Able to do routine blood testing (normal care for transplant recipients)
• Written informed consent obtained from the subject before any trial-related procedures
• Be ≥18 years and ≤75 years of age at time of consent

You may not qualify if:

• Any pre-transplant CMV serologic combinations besides CMV D+/R-
• Multi organ transplants (other than simultaneous liver-kidney transplant (SLK) recipients) or prior history of bone marrow or stem cell transplant
• Lung, heart, small bowel, pancreas, or other non-kidney or non-liver transplant recipients
• Transplant recipients treated for rejection within three months before the end of valganciclovir prophylaxis
• Participation in another interventional clinical trial at time of consent or within 30 days prior to study consent
• Transplant recipients with eGFR \<30 ml/min/1.73m2 (as they theoretically could be at higher risk for renal impairment with CMV immunoglobulin), poor transplant organ function (i.e. LFTs \> twice the upper limit of normal in liver recipients), or who are on dialysis, or plasmapheresis, or who are relisted for transplant, or who might otherwise at risk of complications at the discretion of the local site investigator.
• Those with a history of severe reaction to CMV immunoglobulin (e.g. CytoGam® or similar) or other human immunoglobulin preparations
• Individuals with a history of selective immunoglobulin A deficiency will be excluded, as they may produce antibodies against immunoglobulin A, leading to potential anaphylactic reactions upon receiving blood products containing immunoglobulin A, such as CMV immunoglobulin (e.g. CytoGam® or similar)
• Any history of acute myocardial infarction (within 12 months of screening), clinically significant arrythmia, or clinically significant ECG abnormality in the opinion of the investigator at time of screening
• History of active or latent tuberculosis (except those who have completed a documented regimen for latent TB treatment) or severe pulmonary disease \[e.g., severe pulmonary hypertension (WHO class IV)\] that in the opinion of the investigator that may preclude their ability to safely tolerate study infusions
• Any history of neurodegenerative disease, including dementia, or stroke with substantial residual disability (modified Rankin score ≥ 3)
• Pregnant or nursing (lactating) women confirmed by human chorionic gonadotropin (hCG) laboratory test.
• Women of childbearing potential unless using a highly effective method of contraception during dosing and for 24 weeks after study treatment. Medically acceptable birth control (contraceptives) includes but are not limited to: surgical sterilization (such as hysterectomy or "tubes tied"), approved hormonal contraceptives (such as birth control pills, patch or ring; Depo-Provera, Depo-Lupron, lmplanon), barrier methods (such as condom or diaphragm), an intrauterine device (IUD), abstinence from sex.
• Any significant history of any treatment nonadherence or any other medical condition that, in the investigator's opinion, would confound the results of the study or put the participant at undue risk
• Subjects who have any of the following laboratory values: eGFR \<30 ml/min/1.73m2 ; Hemoglobin \<8.0 g/dL; Platelets \<50,000 cells/uL; Absolute neutrophil count \<1,000 cells/uL; Total bilirubin \>2.5 x upper limit of normal; Alanine aminotransferase (ALT) \>5 x upper limit of normal; Aspartate aminotransferase (AST)\] \>5 x upper limit of normal; CMV IgG negative in donor or positive in recipient

Sponsors & Collaborators

• Camille N. Kotton, MD: lead
• University of Texas Southwestern Medical Center: collaborator
• Kamada, Ltd.: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

University of Texas Southwestern

Dallas, Texas, 75390, United States

RECRUITING

Related Publications (4)

• Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, Humar A; The Transplantation Society International CMV Consensus Group. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation. 2018 Jun;102(6):900-931. doi: 10.1097/TP.0000000000002191.

  PMID: 29596116 BACKGROUND

• Razonable RR, Humar A. Cytomegalovirus in solid organ transplant recipients-Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13512. doi: 10.1111/ctr.13512. Epub 2019 Mar 28.

  PMID: 30817026 BACKGROUND

• McBride JM, Sheinson D, Jiang J, Lewin-Koh N, Werner BG, Chow JKL, Wu X, Tavel JA, Snydman DR. Correlation of Cytomegalovirus (CMV) Disease Severity and Mortality With CMV Viral Burden in CMV-Seropositive Donor and CMV-Seronegative Solid Organ Transplant Recipients. Open Forum Infect Dis. 2019 Jan 14;6(2):ofz003. doi: 10.1093/ofid/ofz003. eCollection 2019 Feb.

  PMID: 30775403 BACKGROUND

• Ljungman P, Chemaly RF, Khawaya F, Alain S, Avery R, Badshah C, Boeckh M, Fournier M, Hodowanec A, Komatsu T, Limaye AP, Manuel O, Natori Y, Navarro D, Pikis A, Razonable RR, Westman G, Miller V, Griffiths PD, Kotton CN; CMV Definitions Working Group of the Transplant Associated Virus Infections Forum. Consensus Definitions of Cytomegalovirus (CMV) Infection and Disease in Transplant Patients Including Resistant and Refractory CMV for Use in Clinical Trials: 2024 Update From the Transplant Associated Virus Infections Forum. Clin Infect Dis. 2024 Sep 26;79(3):787-794. doi: 10.1093/cid/ciae321.

  PMID: 39041385 BACKGROUND

Study Officials

• Camille Kotton, MD, FIDSA, FAST

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• David Wojciechowski, DO

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amelia Stocking, BS

CONTACT

617-643-4087; astocking@mgh.harvard.edu

Camille Kotton, MD

CONTACT

6177240084; ckotton@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open label study so both participants and study doctor will know which arm has been assigned; no placebo infusion is planned.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Camille N. Kotton, MD, Clinical Director of Transplant Infectious Disease

Model Details: This research study will compare CytoGam® used after valganciclovir in D+R- liver, kidney, or liver-kidney transplant recipients to valganciclovir alone. Valganciclovir is used routinely to prevent CMV disease. Qualifying participants are assigned to a study group by chance (like a coin toss) to Arm A, the CytoGam® group or Arm B, the standard of care group. Neither the subject nor the study doctor can choose the study group. Participants will have an equal chance of being assigned to the CytoGam® group.

Study Record Dates

• First Submitted: April 18, 2025
• First Posted: May 6, 2025
• Study Start: November 27, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): May 31, 2028
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Data will be shared during and after the study during data analysis. We anticipate the study will start in May 2025 and supporting information will be available for the following three years.
• Access Criteria: IPD will be available to the investigators at each institution through the REDCap database.

Locations

US (2)