A Study to Evaluate the Efficacy and Safety of a Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seronegative Kidney Transplant Recipients Receiving an Organ From a CMV-Seropositive Donor

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial to Evaluate the Efficacy and Safety of a Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seronegative Kidney Transplant Recipients Receiving an Organ From a CMV-Seropositive Donor

The purpose of this study was to evaluate the efficacy of ASP0113 compared to placebo in reducing the incidence of cytomegalovirus (CMV) viremia in CMV-seronegative subjects receiving a kidney from a CMV-seropositive donor. This study also evaluated the safety of ASP0113 in this patient population.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation Cytomegalovirus (CMV) Negative Recipients
• Intervention / Treatment: Biological: ASP0113; Drug: Placebo

Detailed Description

Participants were followed for one year after first study drug injection. This was the primary study period.

Participants were followed for 4.5 years after completion of the primary study to assess long-term safety of the vaccine.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, NSW 2050
      • Site AU61002
  • Queensland
    • Woolloongabba, Queensland, Australia, QLD 4102
      • Site AU61004
  • South Australia
    • Adelaide SA, South Australia, Australia, 5000
      • Site AU61001
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Site CA15004
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V8
      • Site CA15003
  • Ontario
    • London, Ontario, Canada, N6A 4V2
      • Site CA15005
    • Toronto, Ontario, Canada, M5G2N2
      • Site CA15006
• France
  • Bordeaux, France, 33000
    • Site FR33005
  • Montpellier Cedex 5, France, 34295
    • Site FR33003
  • Nantes, France, 44000
    • Site FR33004
  • Nice, France, 66001
    • Site FR33001
• Germany
  • Berlin, Germany, 10117
    • Site DE49002
  • Berlin, Germany, 13353
    • Site DE49001
  • Bonn, Germany, 53105
    • Site DE49008
  • Erlangen, Germany, 91054
    • Site DE49003
  • Hamburg, Germany, 20246
    • Site DE49005
• Spain
  • Barcelona, Spain, 08003
    • Site ES34003
  • Barcelona, Spain, 08035
    • Site ES34002
  • Barcelona, Spain, 8907
    • Site ES34001
  • Zaragoza, Spain, 50009
    • Site ES34004
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Site US10026
  • California
    • Los Angeles, California, United States, 90057
      • Site US10003
    • San Diego, California, United States, 92123
      • Site US10004
    • San Francisco, California, United States, 94115
      • Site US10036
    • San Francisco, California, United States, 94143
      • Site US10037
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Site US10044
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Site US10018
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Site US10058
    • Atlanta, Georgia, United States, 30322
      • Site US10013
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Site US10030
    • Chicago, Illinois, United States, 60637
      • Site US10009
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Site US10057
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Site US10046
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Site US10041
  • Maine
    • Portland, Maine, United States, 04102
      • Site US10049
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5364
      • Site US10023
    • Detroit, Michigan, United States, 48202
      • Site US10048
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Site US10016
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Site US10015
  • New York
    • Bronx, New York, United States, 10467
      • Site US10012
    • Buffalo, New York, United States, 14215
      • Site US10045
  • North Carolina
    • Greenville, North Carolina, United States, 27858
      • Site US10050
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Site US10001
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Site US10042
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Site US10047
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Site US10027
  • Texas
    • Houston, Texas, United States, 77030
      • Site US10028
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Site US10014
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Site US10038
    • Richmond, Virginia, United States, 23298
      • Site US10031
  • Washington
    • Seattle, Washington, United States, 98101
      • Site US10020
    • Seattle, Washington, United States, 98195-6175
      • Site US10011
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Site US10029

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• CMV negative subject having received a CMV seropositive kidney (living or deceased)
• Participant started valganciclovir or ganciclovir within 10 days of transplant and had received it through Randomization.

Exclusion Criteria:

• Participant underwent a course of CMV-specific prophylactic therapy with antiviral drugs with a duration of greater than 100 days.
• Participant had received from one month prior to transplant or planned to receive CMV immunoglobulin.
• Participant had CMV viremia or CMV disease from time of transplant until time of Randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASP0113; Participants received 1 mL of 5 mg/mL of ASP0113 via injection in the deltoid muscle alternating sides with each dose on days 30, 60, 90, 120 and 180 in relation to the day of transplant (Day 0).	Biological: ASP0113; intramuscular injection
Placebo Comparator: Placebo; Participants received 1 mL of 5 mg/mL of placebo via injection in the deltoid muscle alternating sides with each dose on days 30, 60, 90, 120 and 180 in relation to the day of transplant (Day 0).	Drug: Placebo; intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With CMV Viremia Through 1 Year Post First Study Drug Injection	CMV viremia was defined as presence of cytomegalovirus as measured in plasma viral load of ≥ 1000 IU/mL by central laboratory assay. A participant who discontinued the study without a positive CMV viral load was imputed as having a CMV viremia. A participant who had more than one viral load ≥ 1000 IU/mL by central assay was counted once in this summary. CMV viral loads after first injection (Day 1) through Day 380 (scheduled or unscheduled) were included in the analysis.	From first study dose injection (day 1) up to one year post study drug injection (up to Day 380)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adjudicated CMV-Associated Disease, Including CMV Syndrome and CMV Tissue-Invasive Disease (Primary Study Period)	An independent panel of medical experts reviewed/adjudicated events of CMV-associated disease including CMV syndrome and tissue invasive disease, which were defined according to the American Society of Transplantation Recommendations for Screening, Monitoring and Reporting of Infectious Complications in Immunosuppression Trials in Recipients of Organ Transplantation 2006.	From first study dose injection (day 1) up to one (up to Day 380) year post study drug injection
Percentage of Participants With Plasma Viral Load ≥ The Lower Limit of Quantification (LLOQ) Assessed by Central Laboratory (Primary Study Period)	The central laboratory had the LLOQ level for CMV viral load assessment. When the viral load was below the LLOQ the actual reading was not possible and was denoted as ≤LLOQ. If the participant had any CMV viral load assessments greater than the LLOQ, set up by the central laboratory, participant was classified as viremic and was included in the analysis.	From first study dose injection (day 1) up to one year post study drug injection (up to Day 380)
Percentage of Participants Who Took Adjudicated CMV-specific Antiviral Therapy for the Treatment of CMV Viremia or Disease (Primary Study Period)	An independent panel of medical experts reviewed/adjudicated events of CMV-specific AVT for treatment of CMV viremia or disease.	From first study dose injection (day 1) up to one year post study drug injection (up to Day 380)
Percentage of Participants With Graft Survival (Primary Study Period)	Graft survival was defined for any participant that did not fit the definition of graft loss. Graft loss was defined as participant death, re-transplant, nephrectomy, or return to permanent dialysis (i.e., for > 30 days). Missing values for graft survival were not included in the denominator when making the proportion. The analysis population was the FAS.	From first study dose injection (day 1) up to one year post study drug injection (up to Day 380)
Percentage of Participants With Graft Survival (Long-term Follow up)	Graft survival was defined for any participant that did not fit the definition of graft loss. Graft loss was defined as participant death, re-transplant, nephrectomy, or return to permanent dialysis (i.e., for > 30 days). Missing values for graft survival were not included in the denominator when making the proportion.	Month 18, 30, 42, 54, and 66

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Collaborators: Vical

Publications and helpful links

General Publications

• Vincenti F, Budde K, Merville P, Shihab F, Ram Peddi V, Shah M, Wyburn K, Cassuto-Viguier E, Weidemann A, Lee M, Flegel T, Erdman J, Wang X, Lademacher C. A randomized, phase 2 study of ASP0113, a DNA-based vaccine, for the prevention of CMV in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor. Am J Transplant. 2018 Dec;18(12):2945-2954. doi: 10.1111/ajt.14925. Epub 2018 Jun 20.

Helpful Links

• Link to results and other applicable study documents on the Astellas Clinical Trials website
• Link to plain language summary of the study on the Trial Results Summaries website

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2013
• Primary Completion (Actual): May 13, 2016
• Study Completion (Actual): November 5, 2020

Study Registration Dates

• First Submitted: October 28, 2013
• First Submitted That Met QC Criteria: October 28, 2013
• First Posted (Estimate): November 1, 2013

Study Record Updates

• Last Update Posted (Actual): February 17, 2022
• Last Update Submitted That Met QC Criteria: February 16, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Kidney Transplantation; ASP0113; Cytomegalovirus (CMV)
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections
• Other Study ID Numbers: 0113-CL-2001; 2013-000464-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No