A Study to Evaluate a Therapeutic Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seropositive Recipients Undergoing Allogeneic, Hematopoietic Cell Transplant (HCT)
- Conditions
- Cytomegalovirus (CMV)-Positive RecipientsAllogeneic, Hematopoietic Cell Transplant (HCT)
- Interventions
- Biological: ASP0113Drug: Placebo
- Registration Number
- NCT01877655
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
The purpose of the study was to evaluate the efficacy of ASP0113 compared with placebo as measured by a primary composite endpoint of overall mortality and CMV end organ disease (EOD) through 1 year post-transplant. Safety of ASP0113 in participants undergoing allogeneic HCT will also be evaluated.
- Detailed Description
Participants will be followed for 5.5 years post-transplant for long-term safety via an annual telephone contact.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 514
-
Participant is a CMV-seropositive HCT recipient
-
Participant is planned to undergo either of the following:
- Sibling Donor Transplant
- Unrelated Donor Transplant
-
Participant has one of the following underlying diseases:
- Acute myeloid leukemia (AML)
- Acute lymphoblastic leukemia (ALL)
- Acute undifferentiated leukemia (AUL)
- Acute biphenotypic leukemia
- Chronic myelogenous leukemia (CML)
- Chronic lymphocytic leukemia (CLL).
- A defined myelodysplastic syndrome(s) (MDS)
- Primary or secondary myelofibrosis
- Lymphoma (including Hodgkin's)
- Participant has active CMV disease or infection or has received treatment for active CMV disease or infection within 3 months (90 days) prior to transplant
- Participant has a modified hematopoietic cell transplant comorbidity index (HCT-CI) score ≥ 4
- Participant has received a prior HCT and has residual Chronic Graft-versus-host Disease (cGVHD)
- Participant who is scheduled to have a cord blood transplant or a haploidentical transplant
- Participant has a platelet count of less than 50,000 mm3 within 3 days prior to randomization (platelet transfusions are allowed)
- Participant has aplastic anemia or multiple myeloma
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ASP0113 ASP0113 Participants received 1 mL of 5 mg/mL of ASP0113 via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0). Placebo Placebo Participants received 1 mL of 5 mg/mL of matching placebo via intramuscular injection in the deltoid muscle alternating sides with each dose on days -14 to -3 pretransplant, 14 to 40, 60, 90 and 180 in relation to the day of transplant (Day 0).
- Primary Outcome Measures
Name Time Method Percentage of Participants With Composite of All-Cause Mortality and Adjudicated Cytomegalovirus End Organ Disease (CMV EOD) Through 1 Year Post Transplant From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365) This was the composite of all-cause mortality and adjudicated CMV EOD through 1 year posttransplant, The CMV EOD was assessed by the independent and blinded adjudication committee, which counted events that were observed up to day 380 from transplantation. Deaths that occurred up to day 365 from transplant were also counted.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Protocol-Defined CMV Viremia Through 1 Year Posttransplant From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365) Protocol-defined CMV viremia was defined as a CMV plasma viral load ≥1000 IU/mL as assessed by the central laboratory. Rate was based on cumulative incidence function estimated at 1 year. The central laboratory had the lower limit of quantification \[LLOQ\] for CMV viral load assessment, so when the viral load was below the LLOQ the actual viral load reading was not possible and was denoted as ≤LLOQ. If participant had any CMV viral load assessments greater than the LLOQ it was classified as viremic.
Percentage of Participants With Adjudicated CMV-Specific Antiviral Therapy (AVT) Through 1 Year Posttransplant From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365) The CMV-specific AVT use was adjudicated by the independent and blinded committee. When the CMV-specific AVT was initiated, a central CMV viral load was obtained weekly until it was discontinued. Participants without any CMV-specific AVT events were censored on the last study evaluation.
Percentage of Participants With a Composite Endpoint of Protocol-defined CMV Viremia and Adjudicated CMV-Specific AVT Use From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365) Protocol-defined CMV viremia was as CMV plasma viral load ≥ 1000 IU/mL as assessed by the central laboratory. The CMV-specific AVT was determined by the adjudication committee. Participants with no posttransplant viral load data were excluded from the analysis.
Percentage of Participants With First Occurrence of Adjudicated CMV-specific AVT or Adjudicated Diagnosis of CMV EOD After Study Drug First Injection Through 1 Year Posttransplant From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365) Rate was based on cumulative incidence function estimate at 1 year. Time to first CMV-specific AVT was defined as time to the start of AVT for CMV viremia or CMV EOD. CMV-specific AVT and EOD were determined by the adjudication committee. This endpoint was a composite endpoint based on the independent adjudication committee assessments of CMV-specific AVT and CMV EOD.
All-Cause Mortality at 1 Year Posttransplant From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365) All-cause mortality through 1-year post-transplantation summary included all deaths and unknown survival status. For the known deaths, the adjudication committee assessed results and summarized them according to the following category: Mortality due to the participant's primary disease, and mortality due to causes unrelated to the participant's primary disease. Participants with unknown survival status at 1 year were considered dead for this analysis.
Trial Locations
- Locations (83)
Site US10045
🇺🇸Houston, Texas, United States
Site US10039
🇺🇸Seattle, Washington, United States
Site JP81010
🇯🇵Bunkyo-ku, Tokyo, Japan
Site JP81008
🇯🇵Chuo-ku, Tokyo, Japan
Site TW88602
🇨🇳Taipei City, Taiwan
Site CA15001
🇨🇦Vancouver, British Columbia, Canada
Site US10012
🇺🇸Atlanta, Georgia, United States
Site US10035
🇺🇸San Francisco, California, United States
Site US10016
🇺🇸Nashville, Tennessee, United States
Site US10007
🇺🇸Indianapolis, Indiana, United States
Site CA15004
🇨🇦Montreal, Quebec, Canada
Site CA15003
🇨🇦Quebec, Canada
Site US10028
🇺🇸Birmingham, Alabama, United States
Site US10044
🇺🇸Tucson, Arizona, United States
Site US10026
🇺🇸Stanford, California, United States
Site US10020
🇺🇸Westwood, Kansas, United States
Site US10013
🇺🇸Chicago, Illinois, United States
Site US10030
🇺🇸Tampa, Florida, United States
Site US10011
🇺🇸Baltimore, Maryland, United States
Site US10021
🇺🇸Boston, Massachusetts, United States
Site US10043
🇺🇸Baltimore, Maryland, United States
Site US10010
🇺🇸Louisville, Kentucky, United States
Site US10036
🇺🇸Rochester, Minnesota, United States
Site US10023
🇺🇸Hackensack, New Jersey, United States
Site US10027
🇺🇸Rochester, New York, United States
Site US10042
🇺🇸Saint Louis, Missouri, United States
Site US10047
🇺🇸New York, New York, United States
Site US10024
🇺🇸Seattle, Washington, United States
Site US10031
🇺🇸Richmond, Virginia, United States
Site US10002
🇺🇸Dallas, Texas, United States
Site US10046
🇺🇸Salt Lake City, Utah, United States
Site US10025
🇺🇸Chapel Hill, North Carolina, United States
Site AU43004
🇦🇺Adelaide, South Australia, Australia
Site BE32001
🇧🇪Brugge, Belgium
Site AU43001
🇦🇺Herston, Queensland, Australia
Site US10019
🇺🇸Milwaukee, Wisconsin, United States
Site BE32007
🇧🇪Roeselare, Belgium
Site BE32005
🇧🇪Leuven, Belgium
Site CA15002
🇨🇦Toronto, Ontario, Canada
Site FR33005
🇫🇷Creteil, France
Site FR33011
🇫🇷Besancon, France
Site FR33009
🇫🇷Nantes, France
Site FR33010
🇫🇷Nice, France
Site DE49010
🇩🇪Bonn, Germany
Site DE49014
🇩🇪Koln, Germany
Site DE49013
🇩🇪Gottingen, Germany
Site DE49012
🇩🇪Dusseldorf, Germany
Site DE49002
🇩🇪Leipzig, Germany
Site DE49015
🇩🇪Mainz, Germany
Site DE49007
🇩🇪Muenster, Germany
Site JP81003
🇯🇵Nagoya, Aichi, Japan
Site DE49006
🇩🇪Ulm, Germany
Site DE49008
🇩🇪Tuebingen, Germany
Site DE49005
🇩🇪Stuttgart, Germany
Site DE49001
🇩🇪Wurzburg, Germany
Site JP81007
🇯🇵Sapporo, Hokkaido, Japan
Site JP81011
🇯🇵Maebashi, Gunma, Japan
Site JP81004
🇯🇵Shinjuku-ku, Tokyo, Japan
Site JP81009
🇯🇵Minato-ku, Tokyo, Japan
Site JP81001
🇯🇵Fukuoka, Japan
Site KR82002
🇰🇷Seoul, Korea, Republic of
Site KR82004
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Site JP81005
🇯🇵Fukuoka, Japan
Site KR82003
🇰🇷Seoul, Korea, Republic of
Site JP81006
🇯🇵Osaka, Japan
Site KR82001
🇰🇷Seoul, Korea, Republic of
Site ES34006
🇪🇸Barcelona, Spain
Site ES34001
🇪🇸Badalona, Spain
Site ES34004
🇪🇸Barcelona, Spain
Site ES34005
🇪🇸Cordoba, Spain
Site ES34003
🇪🇸Granada, Spain
Site ES34007
🇪🇸Murcia, Spain
Site ES34011
🇪🇸Madrid, Spain
Site ES34002
🇪🇸Santander, Spain
Site ES34010
🇪🇸Salamanca, Spain
Site SE46001
🇸🇪Gothenburg, Sweden
Site SE46006
🇸🇪Linkoping, Sweden
Site ES34009
🇪🇸Valencia, Spain
Site SE46003
🇸🇪Stockholm, Sweden
Site SE46005
🇸🇪Umea, Sweden
Site SE46004
🇸🇪Lund, Sweden
Site TW88601
🇨🇳Taipei City, Taiwan
Site TW88603
🇨🇳Taoyuan County, Taiwan