Clinical trial NCT06817889: Remdesivir for the Treatment of Upper Respiratory Tract Infection Due to RSV in Immunocompromised Individuals
Official title: An Open-Label Study to Assess the Safety and Efficacy of Remdesivir for Treatment of Symptomatic Laboratory-Confirmed Respiratory Syncytial Virus Infection of the Upper Respiratory Tract in Patients Receiving Cellular or Bispecific Antibody Therapies
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Hematopoietic and Lymphatic System Neoplasm
Lymphoma
Multiple Myeloma
Respiratory Syncytial Virus Infection
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2025-02-10
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial tests how well remdesivir works for treatment of respiratory syncytial virus (RSV) infection of the upper respiratory tract in patients receiving cellular or bispecific antibody therapy. Cellular or bispecific antibody therapies cause suppression of the immune system, making infections more frequent and reducing the body's ability to fight the infections. RSV infections are one of the most common respiratory infections in immunocompromised individuals and can cause significant pneumonia and even death. Remdesivir is in a class of medications called antivirals. It works by stopping viruses from spreading in the body.

Detailed description: OUTLINE:

Patients receive remdesivir intravenously (IV) over 30-120 minutes on days 1-5, with the option to extend to day 10 at the investigator's discretion, in the absence of disease progression or unacceptable toxicity. Patients also undergo nasal swabs and blood sample collection throughout the study.

After completion of study treatment, patients are followed up on day 14 and 29.

Eligibility criteria: Inclusion Criteria:

* Aged ≥ 18 years
* Willing and able to provide written informed consent, or with a legal representative who can provide informed consent (where locally approved)
* RSV confirmed by local lab testing via nucleic acid amplification test (e.g. polymerase chain reaction \[PCR\] or respiratory viral panel \[RVP\]) using an upper respiratory tract sample collected within the 5 days prior to day 1 (RDV dosing)
* Symptomatic RSV infection of the upper respiratory tract, with symptom onset and positive microbiologic testing within the 5 days prior to day 1 (RDV dosing). Symptomatic RSV infection is defined as having new upper respiratory symptom(s) or worsening of a pre-existing upper respiratory symptom (if chronic and associated with a previously existing diagnosis, such as chronic lung disease, chronic rhinorrhea, or seasonal allergies)
* Have one of the following underlying diseases and/or received one of the following treatments relative to RSV diagnosis date:

  * Received allogeneic hematopoietic cell transplant (HCT) with any conditioning regimen within 1 year
  * Received autologous HCT with any conditioning regimen within 3 months
  * Received Chimeric antigen receptor T cell therapy (CARTx) within 3 months
  * Have multiple myeloma (MM) and received bispecific antibody therapy (bsAb) within 3 months
  * Have lymphoma and received bsAb within 3 months
* Categorized as moderate-risk (overall score 3-6) or high-risk (overall score 7-12) per an adapted version of the Immunodeficiency Scoring Index (ISI) for RSV, as below, relative to the day of RSV diagnosis:

  * 1 point:

    * Recent (within the prior 30 days) allogeneic HCT, autologous HCT, or CARTx
    * Corticosteroids within the prior 30 days for management of graft versus host disease (GVHD) or cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS).
  * 2 points:

    * Age ≥ 40 years
  * 3 points:

    * Absolute neutrophil count (ANC) \< 500 cells/μL within the prior 7 days
    * Absolute lymphocyte count (ALC) \< 200 cells/µL within the prior 7 days
* Oxygen saturation (SpO2) 92% or greater on room air and at rest (to be measured after participant has rested in a quiet room for ≥ 2 minutes, with oxygen \[O2\] saturation probe on finger or earlobe for ≥ 1 minute, with saturation reading remaining ≥ 92%) at screening
* Willingness to take study drug and complete necessary study procedures

Exclusion Criteria:

* Received or receiving an approved or authorized direct-acting antiviral therapy with potential efficacy against RSV (e.g. ribavirin) for ≥ 24 hours within the prior 7 days
* Received or receiving investigational direct-acting antiviral therapies against RSV for the current RSV episode
* Received any investigational monoclonal anti-RSV antibodies within \< 4 months or \< 5 half-lives, whichever is longer, before screening
* Received an RSV vaccine after cellular therapy or after starting the current antitumor therapeutic regimen
* Participation in any other concurrent clinical trial of an experimental treatment for RSV, including RSV vaccines
* Alanine aminotransferase (ALT) \> 10 times the upper limit of normal within 7 days prior to screening
* New lower respiratory tract radiographic abnormalities after RSV-associated symptom onset that are suspected to be due to RSV
* Unable to tolerate nasal sampling required for this study, as determined by the investigator (e.g., history of significant epistaxis, nasopharyngeal anatomical abnormalities, nasal or sinus surgery)
* A life expectancy of three months or less, as determined by the investigator
* Pregnant, as determined by a Point-of-Care urine pregnancy test or reported by the patient or their electronic health record within 7 days of screening
* Receiving, requiring, or expected to require supplemental oxygen for RSV-related illness or SpO2 \< 92% at rest \< 24 hours prior to study drug administration
* Previous infection and/or hospitalization for RSV, or previous infection with, treatment for, or hospitalization for another respiratory viral infection within 28 days prior to screening
* Documented positive test for other respiratory viruses concomitantly (limited to influenza, parainfluenza, adenovirus, human metapneumovirus, or coronavirus \[including SARS-CoV-2\]) ≤ 7 days prior to screening, as determined by local testing (additional testing not required)
* Clinically significant bacteremia or fungemia ≤ 7 days prior to screening and not adequately treated, as determined by the investigator
* Clinically significant bacterial, fungal, or viral pneumonia within two (2) weeks prior to screening and not adequately treated, as determined by the investigator
* Clinically significant symptoms of CRS or ICANS within the prior 72 hours before screening that is not adequately controlled, as determined by the investigator
* Any inability to take study drug or comply with study procedures that, in the opinion of the investigator, would make the participant unsuitable for the study
* Known hypersensitivity or allergy to the study drug, its metabolites, or formulation excipients

Primary outcomes:
measure: Proportion of participants requiring ≥ 2 liters/minute of oxygen for ≥ 24 consecutive hours
timeFrame: Up to day 29
Secondary outcomes:
measure: Incidence of treatment-emergent adverse events (AEs) and laboratory abnormalities
timeFrame: Up to day 29
measure: Incidence of serious adverse events and AEs leading to study drug discontinuation
timeFrame: Up to day 29
measure: Proportion of participants with RSV-related hospitalization (if not hospitalized at the time of first dose) or death
timeFrame: Up to day 29
measure: Supplemental oxygen free days
timeFrame: Up to day 29
measure: Proportion of participants who develop new or worsening pulmonary infiltrates
timeFrame: Up to day 29
measure: Proportion of participants requiring high-flow nasal cannula, non-invasive ventilation, or invasive mechanical ventilation for ≥ 24 consecutive hours
timeFrame: Up to day 29
measure: Proportion of participants admitted to intensive care unit
timeFrame: Up to day 29
measure: Proportion of participants who die
timeFrame: Up to day 29
measure: Change from baseline in RSV nasal swab viral load
timeFrame: From baseline through day 3 and 5
measure: Maximum daily Respiratory Infection Intensity and Impact Questionnaire (RiiQ) score
timeFrame: From baseline to day 29
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Joshua Hill, MD
role: PRINCIPAL_INVESTIGATOR
References: