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

NCT05179057 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: P-105-303
• Study Type: interventional
• Target: 57
• Locations: 6 countries
• Sites: 47

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).

Conditions

Adenovirus Infection

Keywords

Allogeneic Hematopoietic Cell Transplant; Adenoviremia; Adenovirus; Stem Cell Transplant; Posoleucel; ALVR105; Bone Marrow Transplant

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (5)

• Number of Participants With Overall Disease Progression

  From Day 29 up to Week 10

• Area Under the Curve (AUC) Adenovirus Viral Load

  Pre-dose and Day 29

• Number of Participants Who Achieved Adenovirus Viremia <400 Copies/mL at Day 29

  Day 29

• Time to Undetectable Adenovirus Viremia (Less Than LLOQ)

  Pre-dose to 34 weeks

• Number of Participants With Adenovirus Disease Recurrence

  34 weeks

Study Arms (2)

Posoleucel + SoC

EXPERIMENTAL

Posoleucel + SOC; then placebo + SOC for patients who meet optional protocol-defined crossover criteria

Drug: Posoleucel

Placebo + SoC

PLACEBO COMPARATOR

Placebo + SOC; then Posoleucel + SOC for patients who meet optional protocol-defined crossover criteria

Drug: Placebo

Interventions

Posoleucel DRUG

Administered as 2-4 milliliter infusion, visually identical to placebo

Posoleucel + SoC

Placebo DRUG

Administered as 2-4 milliliter infusion, visually identical to Posoleucel

Placebo + SoC

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Undergone allogeneic cell transplantation ≥21 days prior to dosing
• Meet one of the below criteria:
• AdV viremia DNA ≥10,000 copies/mL, OR
• AdV viremia DNA results of ≥1,000 copies/mL, AND
• has absolute lymphocyte count \<180/mm3, OR
• has received T cell depletion OR
• had a cord blood transplant.

You may not qualify if:

• 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

Sponsors & Collaborators

• AlloVir: lead

Study Sites (47)

MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of California, Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

Lucile Packard Children's Hospital - Stanford University

Palo Alto, California, 94303, United States

Location

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

San Diego, California, 92123, United States

Location

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

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida (UF) - Gainesville

Gainesville, Florida, 32611, United States

Location

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

Chicago, Illinois, 60611, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

New York Presbyterian Hospital

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Intermountain HealthCare - Primary Children's Hospital

Salt Lake City, Utah, 81432, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98101, United States

Location

The Hospital for Sick Children (SickKids)

Toronto, Ontario, M5G 1X8, Canada

Location

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Fondazione IRCCS San Gerardo dei Tintori

Monza, 20900, Italy

Location

A.O.R.N. Santobono-Pausilipon

Napoli, 80123, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Ospedale Pediatrico Bambino Gesù

Roma, 165, Italy

Location

Ospedale Regina Margherita

Torino, 10126, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento

Verona, 1-37126, Italy

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Sahlgrenska University Hospital

Gothenburg, 41685, Sweden

Location

Skane University Hospital Lund

Lund, 221 85, Sweden

Location

Karolinska University Hospital

Solna, 171 64, Sweden

Location

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

Location

Bristol Royal Hospital for Children

Bristol, BS2 8BJ, United Kingdom

Location

Royal Hospital for Children - Glasgow

Glasgow, G51 4TF, United Kingdom

Location

University College London Hospital

London, NW1 2PG, United Kingdom

Location

St. Mary's Hospital, Paddington

London, W2 1NY, United Kingdom

Location

Great Ormond Street Hospital for Children

London, WC1n 3JH, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

Sheffield Children's NHS Foundation Trust

Sheffield, S10 2TH, United Kingdom

Location

Related Publications (1)

• Vasileiou S, Kuvalekar M, Velazquez Y, Watanabe A, Leen AM, Gilmore SA. Phenotypic and functional characterization of posoleucel, a multivirus-specific T cell therapy for the treatment and prevention of viral infections in immunocompromised patients. Cytotherapy. 2024 Aug;26(8):869-877. doi: 10.1016/j.jcyt.2024.03.012. Epub 2024 Mar 19.

  PMID: 38597860 DERIVED

MeSH Terms

Conditions

Adenoviridae Infections

Condition Hierarchy (Ancestors)

DNA Virus Infections; Virus Diseases; Infections

Limitations and Caveats

The study was discontinued following a pre-planned DSMB futility analysis concluding that the study was unlikely to meet its primary endpoint, no safety concerns were identified.

Results Point of Contact

• Title: Senior Vice President
• Organization: AlloVir, Inc.

rriese@allovir.com

+1 617-433-2605

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study with option for blinded crossover to assess the safety and efficacy of posoleucel as compared to placebo for the treatment of AdV infection in pediatric and adult recipients of HCT with AdV infections receiving SoC.

Study Record Dates

• First Submitted: December 17, 2021
• First Posted: January 5, 2022
• Study Start: April 26, 2022
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2024
• Last Updated: May 8, 2024
• Results First Posted: May 8, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3); CA (2); US (23); SE (3); GB (8); IT (8)