Posoleucel (ALVR105) for the Treatment of Adenovirus Infection in Pediatric and Adult Participants Receiving Standard of Care Following Allogeneic Hematopoietic Cell Transplantation

April 15, 2024 updated by: AlloVir

Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial, With Cross-Over, of Posoleucel (ALVR105) for the Treatment of Adenovirus Infection in Pediatric and Adult Participants Receiving Standard of Care Following Allogeneic Hematopoietic Cell Transplantation

This study will assess the safety and efficacy of Posoleucel for the treatment of adenovirus (AdV) infection in pediatric and adult allo-HCT recipients receiving standard of care (SoC).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

During the period of immune recovery after allogeneic hematopoietic cell transplant (allo-HCT), viral infections and reactivations, including those with AdV, are an important cause of morbidity and mortality. Progression to AdV disease is associated with significant morbidity and mortality rates. This Phase 3, multicenter, randomized, double-blind, placebo-controlled study will assess the safety and efficacy of Posoleucel for the treatment of AdV infection in pediatric and adult allo-HCT recipients receiving SoC.

Study Type

Interventional

Enrollment (Actual)

57

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • The Hospital for Sick Children (SickKids)
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • CHU Sainte-Justine
  • Italy
      • Milano, Italy, 20132
        • IRCCS Ospedale San Raffaele
      • Monza, Italy, 20900
        • Fondazione IRCCS San Gerardo dei Tintori
      • Napoli, Italy, 80123
        • A.O.R.N. Santobono-Pausilipon
      • Padova, Italy, 35128
        • Azienda Ospedaliera di Padova
      • Pavia, Italy, 27100
        • Fondazione IRCCS Policlinico San Matteo
      • Roma, Italy, 165
        • Ospedale Pediatrico Bambino Gesu
      • Torino, Italy, 10126
        • Ospedale Regina Margherita
      • Verona, Italy, 1-37126
        • Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitario Vall d'Hebron
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
      • Valencia, Spain, 46026
        • Hospital Universitari I Politècnic La Fe
  • Sweden
      • Gothenburg, Sweden, 41685
        • Sahlgrenska University Hospital
      • Lund, Sweden, 221 85
        • Skåne University Hospital Lund
      • Solna, Sweden, 171 64
        • Karolinska University Hospital
  • United Kingdom
      • Birmingham, United Kingdom, B4 6NH
        • Birmingham Children's Hospital
      • Bristol, United Kingdom, BS2 8BJ
        • Bristol Royal Hospital for Children
      • Glasgow, United Kingdom, G51 4TF
        • Royal Hospital for Children - Glasgow
      • London, United Kingdom, WC1N 3JH
        • Great Ormond Street Hospital for Children
      • London, United Kingdom, NW1 2PG
        • University College London Hospital
      • London, United Kingdom, W2 1NY
        • St. Mary's Hospital, Paddington
      • Manchester, United Kingdom, M13 9WL
        • Royal Manchester Children's Hospital
      • Sheffield, United Kingdom, S10 2TH
        • Sheffield Children's NHS Foundation Trust
  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • MD Anderson Cancer Center
      • Phoenix, Arizona, United States, 85016
        • Phoenix Children's Hospital
    • California
      • Duarte, California, United States, 91010
        • City Of Hope
      • Los Angeles, California, United States, 90095
        • University of California, Los Angeles (UCLA)
      • Palo Alto, California, United States, 94303
        • Lucile Packard Children's Hospital - Stanford University
      • San Diego, California, United States, 92123
        • University of California, San Diego - Rady Children's Hospital
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado - Center for Cancer and Blood Disorders
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
    • Florida
      • Gainesville, Florida, United States, 32611
        • University of Florida (UF) - Gainesville
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann and Robert H. Lurie Children's Hospital of Chicago
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine in St. Louis
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10032
        • New York Presbyterian Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center
    • Utah
      • Salt Lake City, Utah, United States, 81432
        • Intermountain HealthCare - Primary Children's Hospital
    • Washington
      • Seattle, Washington, United States, 98101
        • Seattle Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Undergone allogeneic cell transplantation ≥21 days prior to dosing

  • Meet one of the below criteria:

    1. AdV viremia DNA ≥10,000 copies/mL, OR

    2. AdV viremia DNA results of ≥1,000 copies/mL, AND

      1. has absolute lymphocyte count <180/mm3, OR
      2. has received T cell depletion OR
      3. had a cord blood transplant.

Exclusion Criteria:

  • Grade 3 or higher acute GVHD
  • Ongoing therapy with high-dose systemic corticosteroids
  • Uncontrolled viral (other than AdV), bacterial, or fungal infection(s)
  • Pregnant or lactating female unwilling to discontinue nursing prior to randomization
  • History of severe prior reactions to blood product transfusions

NOTE: Other protocol-defined inclusion/exclusion criterion may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Posoleucel + SoC
Posoleucel + SOC; then placebo + SOC for patients who meet optional protocol-defined crossover criteria
Drug: Posoleucel
Administered as 2-4 milliliter infusion, visually identical to placebo
Placebo Comparator: Placebo + SoC
Placebo + SOC; then Posoleucel + SOC for patients who meet optional protocol-defined crossover criteria
Drug: Placebo
Administered as 2-4 milliliter infusion, visually identical to Posoleucel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Undetectable Adenovirus Infection
Time Frame: Day 29 through Day 43 (Day 29 + 14 days; up to 43 days post-first infusion)
Viral load of adenovirus was measured at the central laboratory using quantitative polymerase chain reaction (qPCR) from blood and stool samples at each study visit and on Day 29 from a nasopharyngeal swab. There was a 14-day window for participants who crossed over from posoleucel to placebo; and for participants who crossed over from placebo to posoleucel, the pre-dose cross-over Day 1 viral load was used. Participants missing the primary endpoint but having undetectable viremia before Day 29 and after Day 43 were imputed as successes. Undetectable adenovirus viremia was less than the lower limit of quantification (LLOQ).
Day 29 through Day 43 (Day 29 + 14 days; up to 43 days post-first infusion)
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
Time Frame: Up to 34 weeks
A TEAE was defined as an adverse event (AE) with a start date and time on or after the first dose of study treatment. A serious AE (SAE) was an AE that met at least one of the following serious criteria: fatal, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or other important medical event. TEAEs of special interest (AESI) included acute or chronic graft versus host disease, cytokine release syndrome, infusion-related reactions, and graft failure or rejection. Treatment-related refers to the assessment of a relationship between study treatment and the event by the investigator.
Up to 34 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of Participants With Overall Disease Progression
Time Frame: From Day 29 up to Week 10
From Day 29 up to Week 10
Area Under the Curve (AUC) Adenovirus Viral Load
Time Frame: Pre-dose and Day 29
Pre-dose and Day 29
Number of Participants Who Achieved Adenovirus Viremia <400 Copies/mL at Day 29
Time Frame: Day 29
Day 29
Time to Undetectable Adenovirus Viremia (Less Than LLOQ)
Time Frame: Pre-dose to 34 weeks
Pre-dose to 34 weeks
Number of Participants With Adenovirus Disease Recurrence
Time Frame: 34 weeks
34 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AlloVir

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 26, 2022

Primary Completion (Actual)

January 31, 2024

Study Completion (Actual)

January 31, 2024

Study Registration Dates

First Submitted

December 17, 2021

First Submitted That Met QC Criteria

January 4, 2022

First Posted (Actual)

January 5, 2022

Study Record Updates

Last Update Posted (Actual)

May 8, 2024

Last Update Submitted That Met QC Criteria

April 15, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P-105-303

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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