Study of ALVR106 in Patients With Respiratory Viral Infections After Hematopoietic Cell and Solid Organ Transplant

Influenza Infection Clinical Trial

Official title:

Phase 1/2, Double-Blind, Placebo-Controlled, Dose Escalation and Expansion Study of ALVR106 in Addition to Standard of Care for the Treatment of High-Risk Patients With Respiratory Viral Infections After Hematopoietic Cell and Solid Organ Transplant

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04933968
• Other study ID #: P-106-001
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: March 21, 2022
• Est. completion date: January 31, 2024

Study information

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

Clinical Trial Summary

A study to evaluate ALVR106; an allogeneic, off-the-shelf multi-virus specific T cell therapy that targets four community acquired respiratory viruses: respiratory syncytial virus (RSV), influenza, human metapneumovirus (hMPV), and/or parainfluenza virus (PIV) following hematopoietic cell transplant (HCT) and solid organ transplant (SOT).

Description:

The study hypothesis is that the administration of ALVR106, multi-virus specific T cells, plus standard of care, to post HCT or SOT patients suffering from infection with any of the four targeted viruses (RSV, influenza, hMPV, and/or PIV) will be safe and demonstrate shorter time to resolution of the respiratory viral infection (as measured by resolution of symptoms and viral load clearance in nasal swab) compared to patients treated with placebo.

This trial will consist of two parts: Part A is Dose Escalation and Part B is Cohort Expansion.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 17
• Est. completion date: January 31, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 17 Years to 75 Years

Eligibility

Inclusion Criteria:

• Undergone hematopoietic cell transplantation (HCT) =21 days or solid organ transplantation (SOT) =28 days prior to study treatment administration

• Detection of at least 1 target virus of interest (ie, RSV, influenza, hMPV, and/or PIV)

• Diagnosis of Upper or mild Lower Respiratory Tract Infection

Exclusion Criteria:

• Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose >0.5 mg/kg/day)

• Infection by novel coronavirus disease 2019 (COVID-19)

• For HCT patients, evidence of Grade >2 GVHD; and for SOT patients, any history or evidence of GVHD

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Influenza Infection
• Paramyxoviridae Infections
• Virus Diseases

Intervention

Biological:
• ALVR106
Infusion, visually identical to placebo
• Placebo
Infusion, visually identical to ALVR106

Locations

Country	Name	City	State
United States	Northside Hospital	Atlanta	Georgia
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	University of North Carolina - Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	City of Hope	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Florida - Division of Hematology & Oncology	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	MD Anderson	Houston	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Miami - Sylvester Cancer Center	Miami	Florida
United States	Froedtert Hospital and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt University Cancer Center	Nashville	Tennessee
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Scottsdale Healthcare Hospitals DBA HonorHealth	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Wake Forest	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AlloVir

Country where clinical trial is conducted

United States, 

References & Publications (1)

Vasileiou S, Turney AM, Kuvalekar M, Mukhi SS, Watanabe A, Lulla P, Ramos CA, Naik S, Vera JF, Tzannou I, Leen AM. Rapid generation of multivirus-specific T lymphocytes for the prevention and treatment of respiratory viral infections. Haematologica. 2020 Jan;105(1):235-243. doi: 10.3324/haematol.2018.206896. Epub 2019 Apr 19. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A)	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, requires in-patient 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 new/worsening graft versus host disease, graft failure or rejection, cytokine release syndrome, infusion related reactions, new/worsening pneumonitis, and progressive dyspnea. Treatment-related refers to the assessment of a relationship between study treatment and the event by the investigator.	Day 1 up to 12 months
Primary	Change in Viral Load From Baseline to Day 28 (Part B)	Change from Baseline in viral load as measured by quantitative PCR of nasal swab	Baseline and Day 28 (Part B)
Secondary	Identify the Recommended Phase 2 Dose (RP2D) (Part A)	The RP2D was to be determined after the maximum tolerated dose was reached in Part A.	Day 1 up to 12 months
Secondary	Change in Viral Load Cycle Threshold From Baseline to Day 28 (Part A)	Viral load was measured by quantitative polymerase chain reaction (PCR) of nasal swab specimens. The cycle threshold value categorizes the concentration of viral genetic material in a participant's swab specimen, and the cycle threshold value represents the number of PCR cycles required to amplify the viral genetic material (as measured by fluorescence) to a detectable level that is distinguishable from baseline fluorescence, providing an estimate of viral load. Lower cycle threshold values indicate higher viral load and high values indicate lower viral load. A positive change from baseline indicates a decrease in the viral load. The baseline measurement was from a pre-dose nasal swab.	Baseline and Day 28
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part B)		Day 1 up to 12 months
Secondary	Percentage Reduction in Viral Load From Baseline to Month 6 (Part B)		Day 1 and Month 6