A Study to Evaluate a Therapeutic Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seropositive Recipients Undergoing Allogeneic, Hematopoietic Cell Transplant (HCT) (HELIOS)

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Evaluate the Protective Efficacy and Safety of a Therapeutic Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seropositive Recipients Undergoing Allogeneic, Hematopoietic Cell Transplant (HCT)

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.

Study Overview

• Status: Completed
• Conditions: Cytomegalovirus (CMV)-Positive Recipients; Allogeneic, Hematopoietic Cell Transplant (HCT)
• Intervention / Treatment: Drug: Placebo; Biological: ASP0113

Detailed Description

Participants will be followed for 5.5 years post-transplant for long-term safety via an annual telephone contact.

• Study Type: Interventional
• Enrollment (Actual): 514
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, QLD 4029
      • Site AU43001
  • South Australia
    • Adelaide, South Australia, Australia, SA 5000
      • Site AU43004
• Belgium
  • Brugge, Belgium, 8000
    • Site BE32001
  • Leuven, Belgium, 3000
    • Site BE32005
  • Roeselare, Belgium, 8800
    • Site BE32007
• Canada
  • Quebec, Canada, G1R 2J6
    • Site CA15003
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Site CA15001
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Site CA15002
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • Site CA15004
• France
  • Besancon, France, 25030
    • Site FR33011
  • Creteil, France, 94000
    • Site FR33005
  • Nantes, France, 44093
    • Site FR33009
  • Nice, France, 06200
    • Site FR33010
• Germany
  • Bonn, Germany, 53127
    • Site DE49010
  • Dusseldorf, Germany, 40225
    • Site DE49012
  • Gottingen, Germany, 37075
    • Site DE49013
  • Koln, Germany, 50937
    • Site DE49014
  • Leipzig, Germany, 04103
    • Site DE49002
  • Mainz, Germany, 55131
    • Site DE49015
  • Muenster, Germany, 48149
    • Site DE49007
  • Stuttgart, Germany, 70376
    • Site DE49005
  • Tuebingen, Germany, 72076
    • Site DE49008
  • Ulm, Germany, 89081
    • Site DE49006
  • Wurzburg, Germany, 97080
    • Site DE49001
• Japan
  • Fukuoka, Japan
    • Site JP81005
  • Fukuoka, Japan
    • Site JP81001
  • Osaka, Japan
    • Site JP81006
  • Aichi
    • Nagoya, Aichi, Japan
      • Site JP81003
  • Gunma
    • Maebashi, Gunma, Japan
      • Site JP81011
  • Hokkaido
    • Sapporo, Hokkaido, Japan
      • Site JP81007
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan
      • Site JP81010
    • Chuo-ku, Tokyo, Japan
      • Site JP81008
    • Minato-ku, Tokyo, Japan
      • Site JP81009
    • Shinjuku-ku, Tokyo, Japan
      • Site JP81004
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Site KR82002
  • Seoul, Korea, Republic of, 110744
    • Site KR82003
  • Seoul, Korea, Republic of, 137-701
    • Site KR82001
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 06351
      • Site KR82004
• Spain
  • Badalona, Spain, 08615
    • Site ES34001
  • Barcelona, Spain, 08041
    • Site ES34006
  • Barcelona, Spain, 08908
    • Site ES34004
  • Cordoba, Spain, 14004
    • Site ES34005
  • Granada, Spain, 18012
    • Site ES34003
  • Madrid, Spain, 28028
    • Site ES34011
  • Murcia, Spain, 30008
    • Site ES34007
  • Salamanca, Spain, 37007
    • Site ES34010
  • Santander, Spain, 39008
    • Site ES34002
  • Valencia, Spain, 46010
    • Site ES34009
• Sweden
  • Gothenburg, Sweden, 413 45
    • Site SE46001
  • Linkoping, Sweden, 581 85
    • Site SE46006
  • Lund, Sweden, 221 85
    • Site SE46004
  • Stockholm, Sweden, 14186
    • Site SE46003
  • Umea, Sweden, 901 85
    • Site SE46005
• Taiwan
  • Taipei City, Taiwan, 10002
    • Site TW88601
  • Taipei City, Taiwan, 11217
    • Site TW88602
  • Taoyuan County, Taiwan, 33305
    • Site TW88603
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Site US10028
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Site US10044
  • California
    • San Francisco, California, United States, 94143
      • Site US10035
    • Stanford, California, United States, 94305
      • Site US10026
  • Florida
    • Tampa, Florida, United States, 33612
      • Site US10030
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Site US10012
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Site US10013
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Site US10007
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Site US10020
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Site US10010
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Site US10043
    • Baltimore, Maryland, United States, 21205
      • Site US10011
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Site US10021
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Site US10036
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Site US10042
  • New Jersey
    • Hackensack, New Jersey, United States, 07601-2105
      • Site US10023
  • New York
    • New York, New York, United States, 10032
      • Site US10047
    • Rochester, New York, United States, 14642
      • Site US10027
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Site US10025
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Site US10016
  • Texas
    • Dallas, Texas, United States, 75246
      • Site US10002
    • Houston, Texas, United States, 77030
      • Site US10045
  • Utah
    • Salt Lake City, Utah, United States, 84143
      • Site US10046
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Site US10031
  • Washington
    • Seattle, Washington, United States, 98108
      • Site US10039
    • Seattle, Washington, United States, 98109
      • Site US10024
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Site US10019

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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 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 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).	Biological: ASP0113; Intramuscular injection
Placebo Comparator: 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).	Drug: Placebo; Intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Composite of All-Cause Mortality and Adjudicated Cytomegalovirus End Organ Disease (CMV EOD) Through 1 Year Post Transplant	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.	From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Protocol-Defined CMV Viremia Through 1 Year Posttransplant	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.	From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365)
Percentage of Participants With Adjudicated CMV-Specific Antiviral Therapy (AVT) Through 1 Year Posttransplant	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.	From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365)
Percentage of Participants With a Composite Endpoint of Protocol-defined CMV Viremia and Adjudicated CMV-Specific AVT Use	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.	From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365)
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	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.	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 at 1 Year Posttransplant	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.	From first study dose injection (Day -14 to -3 prior to transplant) up to one year post study drug injection (Day 365)

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Investigators: Study Director: Medical Director, Astellas Pharma Global Development, Inc.

Publications and helpful links

General Publications

• Ljungman P, Bermudez A, Logan AC, Kharfan-Dabaja MA, Chevallier P, Martino R, Wulf G, Selleslag D, Kakihana K, Langston A, Lee DG, Solano C, Okamoto S, Smith LR, Boeckh M, Wingard JR, Cywin B, Fredericks C, Lademacher C, Wang X, Young J, Maertens J. A randomised, placebo-controlled phase 3 study to evaluate the efficacy and safety of ASP0113, a DNA-based CMV vaccine, in seropositive allogeneic haematopoietic cell transplant recipients. EClinicalMedicine. 2021 Mar 19;33:100787. doi: 10.1016/j.eclinm.2021.100787. eCollection 2021 Mar.

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): September 11, 2013
• Primary Completion (Actual): September 28, 2017
• Study Completion (Actual): March 1, 2022

Study Registration Dates

• First Submitted: June 12, 2013
• First Submitted That Met QC Criteria: June 12, 2013
• First Posted (Estimated): June 14, 2013

Study Record Updates

• Last Update Posted (Actual): October 24, 2024
• Last Update Submitted That Met QC Criteria: October 15, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Hematopoietic Cell Transplant (HCT); ASP0113; Cytomegalovirus (CMV)
• Additional Relevant MeSH Terms: Infections; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections
• Other Study ID Numbers: 0113-CL-1004; 2013-000903-18 (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 products 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. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• 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; SAP; CSR