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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 5
- 主要终点
- Proportion of participants requiring ≥ 2 liters/minute of oxygen for ≥ 24 consecutive hours
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
- •Receiving treatment for a refractory or relapsed hematologic malignancy, or received a hematopoietic cell transplant (HCT), chimeric antigen receptor T cell therapy (CARTx), or bispecific antibody (bsAb) therapy within the past 365 days (relative to RSV diagnosis date)
- •Categorized as moderate-risk (overall score 3-6) or high-risk (overall score 7-10) per an adapted version of the Immunodeficiency Scoring Index (ISI) for RSV, as below, relative to the day of RSV diagnosis:
- •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) 93% 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 ≥ 93%) at screening
- •Willingness to take study drug and complete necessary study procedures
- •Participants of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described
排除标准
- •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, and/or expected to receive anti-RSV direct-acting antiviral therapies for RSV during the course of the study at the time of screening
- •Received or receiving investigational direct-acting antiviral therapies against RSV for the current RSV episode
- •Received any investigational anti-RSV monoclonal antibodies or off-label use of approved anti-RSV monoclonal antibodies within < 4 months or < 5 half-lives, whichever is longer, before screening, or expected to receive anti-RSV monoclonal antibodies during the course of the study at the time of 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) ≥ 5 times the upper limit of normal within 7 days prior to screening
- •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 < 93% at rest < 24 hours prior to study drug administration
- •Previous infection or treatment for RSV, or previous treatment or hospitalization for another respiratory viral infection, < 28 days before 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
研究组 & 干预措施
Treatment (remdesivir)
Patients receive remdesivir 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.
干预措施: Survey Administration (Other)
Treatment (remdesivir)
Patients receive remdesivir 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.
干预措施: Biospecimen Collection (Procedure)
Treatment (remdesivir)
Patients receive remdesivir 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.
干预措施: Nasal Swab (Procedure)
Treatment (remdesivir)
Patients receive remdesivir 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.
干预措施: Remdesivir (Drug)
结局指标
主要结局
Proportion of participants requiring ≥ 2 liters/minute of oxygen for ≥ 24 consecutive hours
时间窗: Up to day 29
Will be estimated with 95% Wilson confidence intervals.
次要结局
- Incidence of treatment-emergent adverse events (AEs) and laboratory abnormalities(Up to day 29)
- Incidence of serious adverse events and AEs leading to study drug discontinuation(Up to day 29)
- Proportion of participants with RSV-related hospitalization (if not hospitalized at the time of first dose) or death(Up to day 29)
- Supplemental oxygen free days(Up to day 29)
- Proportion of participants who develop new or worsening pulmonary infiltrates(Up to day 29)
- Proportion of participants requiring high-flow nasal cannula, non-invasive ventilation, or invasive mechanical ventilation for ≥ 24 consecutive hours(Up to day 29)
- Proportion of participants admitted to intensive care unit(Up to day 29)
- Proportion of participants who die(Up to day 29)
- Change from baseline in RSV nasal swab viral load(From baseline through day 3 and 5)
- Maximum daily Respiratory Infection Intensity and Impact Questionnaire (RiiQ) score(From baseline to day 29)