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

Phase 3
Terminated
Conditions
Adenovirus Infection
Interventions
Drug: Placebo
Registration Number
NCT05179057
Lead Sponsor
AlloVir
Brief Summary

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).

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
57
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo + SoCPlaceboPlacebo + SOC; then Posoleucel + SOC for patients who meet optional protocol-defined crossover criteria
Posoleucel + SoCPosoleucelPosoleucel + SOC; then placebo + SOC for patients who meet optional protocol-defined crossover criteria
Primary Outcome Measures
NameTimeMethod
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)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.

Number of Participants With Undetectable Adenovirus InfectionDay 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).

Secondary Outcome Measures
NameTimeMethod
Area Under the Curve (AUC) Adenovirus Viral LoadPre-dose and Day 29
Number of Participants Who Achieved Adenovirus Viremia <400 Copies/mL at Day 29Day 29
Number of Participants With Overall Disease ProgressionFrom Day 29 up to Week 10
Time to Undetectable Adenovirus Viremia (Less Than LLOQ)Pre-dose to 34 weeks
Number of Participants With Adenovirus Disease Recurrence34 weeks

Trial Locations

Locations (47)

University of California, Los Angeles (UCLA)

🇺🇸

Los Angeles, California, United States

Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

Ann and Robert H. Lurie Children's Hospital of Chicago

🇺🇸

Chicago, Illinois, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Seattle Children's Hospital

🇺🇸

Seattle, Washington, United States

Children's Hospital Colorado - Center for Cancer and Blood Disorders

🇺🇸

Aurora, Colorado, United States

Phoenix Children's Hospital

🇺🇸

Phoenix, Arizona, United States

CHU Sainte-Justine

🇨🇦

Montreal, Quebec, Canada

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Fondazione IRCCS San Gerardo dei Tintori

🇮🇹

Monza, Italy

University of Oklahoma

🇺🇸

Oklahoma City, Oklahoma, United States

MD Anderson Cancer Center

🇺🇸

Gilbert, Arizona, United States

Children's National Medical Center

🇺🇸

Washington, District of Columbia, United States

University of California, San Diego - Rady Children's Hospital

🇺🇸

San Diego, California, United States

University of Florida (UF) - Gainesville

🇺🇸

Gainesville, Florida, United States

Lucile Packard Children's Hospital - Stanford University

🇺🇸

Palo Alto, California, United States

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

New York Presbyterian Hospital

🇺🇸

New York, New York, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

University of Texas Southwestern

🇺🇸

Dallas, Texas, United States

Cook Children's Medical Center

🇺🇸

Fort Worth, Texas, United States

The Hospital for Sick Children (SickKids)

🇨🇦

Toronto, Ontario, Canada

IRCCS Ospedale San Raffaele

🇮🇹

Milano, Italy

Ospedale Pediatrico Bambino Gesù

🇮🇹

Roma, Italy

A.O.R.N. Santobono-Pausilipon

🇮🇹

Napoli, Italy

Ospedale Regina Margherita

🇮🇹

Torino, Italy

Hospital Universitari i Politecnic La Fe

🇪🇸

Valencia, Spain

Sahlgrenska University Hospital

🇸🇪

Gothenburg, Sweden

Azienda Ospedaliera di Padova

🇮🇹

Padova, Italy

Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento

🇮🇹

Verona, Italy

Fondazione IRCCS Policlinico San Matteo

🇮🇹

Pavia, Italy

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Bristol Royal Hospital for Children

🇬🇧

Bristol, United Kingdom

Karolinska University Hospital

🇸🇪

Solna, Sweden

Birmingham Children's Hospital

🇬🇧

Birmingham, United Kingdom

Skane University Hospital Lund

🇸🇪

Lund, Sweden

Royal Hospital for Children - Glasgow

🇬🇧

Glasgow, United Kingdom

Great Ormond Street Hospital for Children

🇬🇧

London, United Kingdom

Royal Manchester Children's Hospital

🇬🇧

Manchester, United Kingdom

University College London Hospital

🇬🇧

London, United Kingdom

St. Mary's Hospital, Paddington

🇬🇧

London, United Kingdom

Hospital Universitario Vall d'Hebron

🇪🇸

Barcelona, Spain

City of Hope

🇺🇸

Duarte, California, United States

Washington University School of Medicine in St. Louis

🇺🇸

Saint Louis, Missouri, United States

Intermountain HealthCare - Primary Children's Hospital

🇺🇸

Salt Lake City, Utah, United States

Sheffield Children's NHS Foundation Trust

🇬🇧

Sheffield, United Kingdom

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

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