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

Adenovirus Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05179057
• Other study ID #: P-105-303
• Status: Terminated
• Phase: Phase 3
• Start date: April 26, 2022
• Est. completion date: January 31, 2024

Study information

• Verified date: April 2024
• Source: AlloVir
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Terminated
• Enrollment: 57
• Est. completion date: January 31, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenoviridae Infections
• Adenovirus Infection
• Communicable Diseases
• Infections

Intervention

Drug:
• Posoleucel
Administered as 2-4 milliliter infusion, visually identical to placebo
• Placebo
Administered as 2-4 milliliter infusion, visually identical to Posoleucel

Locations

Country	Name	City	State
Canada	CHU Sainte-Justine	Montreal	Quebec
Canada	The Hospital for Sick Children (SickKids)	Toronto	Ontario
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza
Italy	A.O.R.N. Santobono-Pausilipon	Napoli
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Ospedale Pediatrico Bambino Gesù	Roma
Italy	Ospedale Regina Margherita	Torino
Italy	Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento	Verona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Sweden	Sahlgrenska University Hospital	Gothenburg
Sweden	Skane University Hospital Lund	Lund
Sweden	Karolinska University Hospital	Solna
United Kingdom	Birmingham Children's Hospital	Birmingham
United Kingdom	Bristol Royal Hospital for Children	Bristol
United Kingdom	Royal Hospital for Children - Glasgow	Glasgow
United Kingdom	Great Ormond Street Hospital for Children	London
United Kingdom	St. Mary's Hospital, Paddington	London
United Kingdom	University College London Hospital	London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United Kingdom	Sheffield Children's NHS Foundation Trust	Sheffield
United States	Children's Hospital Colorado - Center for Cancer and Blood Disorders	Aurora	Colorado
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	City of Hope	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Florida (UF) - Gainesville	Gainesville	Florida
United States	MD Anderson Cancer Center	Gilbert	Arizona
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	University of California, Los Angeles (UCLA)	Los Angeles	California
United States	University of Minnesota	Minneapolis	Minnesota
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York Presbyterian Hospital	New York	New York
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	Lucile Packard Children's Hospital - Stanford University	Palo Alto	California
United States	Phoenix Children's Hospital	Phoenix	Arizona
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	University of California, San Diego - Rady Children's Hospital	San Diego	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
AlloVir

Countries where clinical trial is conducted

United States,  Canada,  Italy,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Undetectable Adenovirus Infection	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)
Primary	Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	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	Number of Participants With Overall Disease Progression		From Day 29 up to Week 10
Secondary	Area Under the Curve (AUC) Adenovirus Viral Load		Pre-dose and Day 29
Secondary	Number of Participants Who Achieved Adenovirus Viremia <400 Copies/mL at Day 29		Day 29
Secondary	Time to Undetectable Adenovirus Viremia (Less Than LLOQ)		Pre-dose to 34 weeks
Secondary	Number of Participants With Adenovirus Disease Recurrence		34 weeks