A Study of MCMV5322A/MCMV3068A for the Prevention of Cytomegalovirus Disease in High-Risk Kidney Allograft Recipients

Study Overview
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Brief Summary
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This is a Phase II, randomized, double-blind, placebo-controlled study designed to assess the safety and clinical activity of multiple intravenous doses of MCMV5322A/MCMV3068A in cytomegalovirus (CMV)-seronegative recipients of a renal transplant from a CMV-seropositive donor, with use of a preemptive approach for prevention of CMV disease. Participants will be randomized into two treatment groups: active or placebo control; both arms will be followed preemptively. The study has a planned enrollment of approximately 120 participants (60 active and 60 placebo).

Official Title
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A Phase II Randomized, Double-blind, Placebo-controlled Trial of MCMV5322A/MCMV3068A for the Prevention of Cytomegalovirus Disease in High-risk Kidney Allograft Recipients

Conditions
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Cytomegalovirus Infections

Intervention / Treatment
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* Drug: MCMV3068A
* Drug: MCMV5322A
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is scheduled to receive a primary or secondary renal allograft from a donor Participant is seronegative for CMV and is receiving an allograft from a CMV-seropositive donor Female participants of child-bearing age must have a negative pregnancy test result on Day 1, prior to infusion For women who are not postmenopausal or surgically sterile (defined as absence of ovaries and/or uterus): agreement to remain completely abstinent or use two methods of contraception at all times Exclusion Criteria: Participant is suspected of having CMV disease Participant has received anti-CMV therapy within the 30 days prior to screening (exceptions are the use of acyclovir, valacyclovir, or famciclovir for up to 10 days duration for treatment of acute herpes simplex or herpes zoster or participants receiving acyclovir or valacyclovir at doses to suppress herpes zoster) Participants who have received intravenous immunoglobulin (IVIG) within 3 months before transplantation or with expectation of receiving IVIG at time of transplantation or in the 3 months after transplantation Participants who have received B cell-depleting therapies (including but not limited to rituximab) within 3 months before transplantation or with the expectation of receiving such therapy at the time of transplantation or in the 3 months after transplantation Participant is receiving a multi-organ transplant (e.g., liver or pancreas in addition to kidney) Active or chronic hepatic or hepatobiliary disease (including known Gilbert's syndrome) or elevations in a hepatic transaminase or bilirubin >= 2 times upper limits of normal (ULN) Participant is unlikely or unwilling to be available for follow-up for the full 24-week duration of the study Female participants who are pregnant, plan to become pregnant during the study, or who are breastfeeding History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins or human-derived immunoglobulin preparations; or any constituent of MCMV5322A/MCMV3068A or placebo Active treatment for untreated tuberculosis or other infectious conditions that are significant in the judgment of the investigator Infection with hepatitis B, hepatitis C or human immunodeficiency virus Previous exposure to any investigational agent within 12 weeks or 5 half-lives Any other acute or chronic condition, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that, in the opinion of the Principal Investigator, contraindicates the use of an investigational drug or that may affect the interpretation of the results or that renders the participant at high risk for treatment complications History of alcoholism or substance abuse within 6 months before screening Participant is expected to require treatment or prophylaxis with an antiviral with anti-CMV activity during the study

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: Treatment
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MCMV5322A/MCMV3068A<br>Participants will receive a total of four doses of study drug administered by intravenous infusion: at the time of transplantation (Day 1), and at Days 8, 29, and 57. MCMV5322A/MCMV3068A will be tested in this study at 10 milligrams per kilogram (mg/kg) of each component antibody. Thus, at each dose, 10 mg/kg of MCMV5322A and 10 mg/kg of MCMV3068A will be tested (20 mg/kg total). | Drug: MCMV3068A<br>* Four doses of MCMV3068A (10 mg/kg) administered by intravenous infusion at the time of transplantation (Day 1), and at Days 8, 29, and 57.<br>Drug: MCMV5322A<br>* Four doses of MCMV5322A (10 mg/kg) administered by intravenous infusion at the time of transplantation (Day 1), and at Days 8, 29, and 57.<br>|
| Placebo Comparator: Placebo<br>Participants will receive a total of four doses of placebo matched with MCMV5322A/MCMV3068A administered by intravenous infusion: at the time of transplantation (Day 1), and at Days 8, 29, and 57. | Drug: Placebo<br>* Four doses of placebo matched to MCMV5322A/MCMV3068A administered by intravenous infusion at the time of transplantation (Day 1), and at Days 8, 29, and 57.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events |  | Baseline up to Week 24 | 
| Percentage of Participants With CMV Viral Load Greater than or Equal to (>=) 150 Copies per Milliliter (Copies/mL) During the First 12 Weeks After Transplantation |  | Baseline up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With CMV Viral Load >= 150 Copies/mL During the First 24 Weeks After Transplantation |  | Baseline up to Week 24 | 
| Time to Detectable CMV Viral Load >=150 Copies/mL |  | Baseline up to Week 24 | 
| Viral Load at the First Detection of CMV DNAemia (>=150 Copies/mL), DNAemia is detection of deoxyribonucleic acid (DNA) |  | Baseline up to Week 24 | 
| Peak Viral Load on or Following First Detection of CMV DNAemia (>=150 Copies/mL) |  | Baseline up to Week 24 | 
| Percentage of Participants who Require Initiation of Pre-emptive Antiviral Therapy During the First 12 Weeks and 24 Weeks After Transplantation |  | Baseline up to Weeks 12 and 24 | 
| Time to Initiation of First use of Preemptive Antiviral Therapy |  | Baseline up to Week 24 | 
| Duration of First use of Preemptive Antiviral Therapy Initiated During the First 12 and 24 Weeks After Transplantation |  | Baseline up to Weeks 12 and 24 | 
| Percentage of Participants With CMV Syndrome or Tissue-Invasive CMV Disease During the First 24 Weeks After Transplantation |  | Baseline up to Week 24 | 
| Percentage of Participants With Change in CMV Serostatus |  | Baseline up to Week 24 | 
| MCMV5322A Serum Concentrations |  | Up to 24 hours prior to dosing (Day 1) and 1, 4, 24, and 72 hours postdose; predose (0 hours) and 1 hour postdose on Days 8, 29, 57; on Days 43, 58, 64, 71, 78, 85, 113, and 141; at study completion (Day 169) | 
| MCMV3068A Serum Concentrations |  | Up to 24 hours prior to dosing (Day 1) and 1, 4, 24, and 72 hours postdose; predose (0 hours) and 1 hour postdose on Days 8, 29, 57; on Days 43, 58, 64, 71, 78, 85, 113, and 141; at study completion (Day 169) | 
| Percentage of Participants With Anti-therapeutic Antibodies (ATAs) to MCMV5322A and MCMV3068A |  | Predose (0 hours) on Days 1, 29, 57; at Days 85, 113, and 141; and at Study Completion (Day 169) |