Randomized, Double-blind, Placebo-controlled Trial of the Safety, Tolerability, and Efficacy of RV521 in the Treatment of Adult Subjects Who Have Undergone Hematopoietic Cell Transplantation (HCT) With a Documented Upper Respiratory Tract Infection (URTI) With Respiratory Syncytial Virus (RSV)
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- Pfizer
- 主要终点
- Change in RSV nasal viral load (via RT-qPCR)
研究概览
简要总结
RV521 is to being developed to treat RSV infection and disease in susceptible individuals at high risk for complications. This is an international, multicenter, placebo-controlled study. Eligible subjects are adults with a documented symptomatic RSV infection who have undergone HCT transplantation and are moderately to severely immunocompromised. Qualified subjects will be randomized in a 1:1 ratio to receive RV521 or placebo, twice daily for 10 days.
详细描述
The purpose of this study is to compare the viral load, safety, tolerability, and clinical efficacy of RV521 compared to placebo. This is a Phase 2, international, multicenter, randomized, double-blind, placebo-controlled study. Up to 200 adult subjects with a documented symptomatic RSV URTI who have undergone HCT within 1 year of randomization and who are moderately to severely immunocompromised will be randomized.
Qualified subjects will be randomized in a 1:1 ratio to receive RV521 capsules or matching placebo twice daily for 10 days. After the completion of the 10-day double-blind treatment period, subjects will be followed for an additional 28 days. Study drug may be taken on an outpatient or inpatient basis, depending on clinical status and site practices. Randomization will be stratified by type of HCT graft and ALC count. There are 9 clinic visits planned for this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The Investigators, Sponsor, Independent Adjudication Committee members, and any personnel involved in the subject's care, assessment, monitoring, data collection, or analysis will be blinded to the subject treatment assignment throughout the conduct of the study. Exceptions to this are limited to a fire-walled-protected, unblinded Data Safety Monitoring Board (DSMB) statistician at the Contract Research Organization (CRO) who will prepare output for the closed session of all DSMB meetings.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has undergone autologous or allogeneic HCT using any conditioning regimen within 1 year of randomization. Subjects who have undergone HCT more than 1 year before Randomization are eligible if all other inclusion/exclusion criteria are satisfied and under at least one of the following conditions:
- •Diagnosed with Chronic Graft-vs-Host Disease (GVHD), or
- •Has used systemic corticosteroids in the 30 days prior to RSV infection
- •Has moderate to severe immunocompromise, defined as a score ≥ 5 on the ISI-RSV and/or an ALC of ≤ 500 cells/ mm3
- •Documentation of positive RSV infection in the upper airway
排除标准
- •Use of non-marketed investigational agents within 30 days, OR use of an investigational monoclonal anti-RSV antibodies within 4 months or 5 half-lives of screening, whichever is longer, OR use of any investigational RSV vaccines after HCT.
- •Receiving a prescription, OTC, or herbal medication that is a potent inducer or inhibitor of CYP3A4, within 2 weeks of Randomization.
- •Receiving a prescription, OTC, or herbal medication that is a substrate of CYP3A4 with a narrow therapeutic index where monitoring blood levels is not possible.
- •Known chronic infection with hepatitis B, C, or HIV.
- •Is in the pre-engraftment period during RSV infection.
- •Admitted to the hospital primarily for lower respiratory tract disease of any cause as determined by the Investigator.
- •Any condition requiring mechanical ventilation or vasopressor support at the time of randomization.
- •Clinically significant bacteremia or fungemia within 5 days prior to Screening that has not been adequately treated.
- •Clinically significant bacterial, fungal, or viral pneumonia within 2 weeks prior to Screening that has not been adequately treated.
- •Excessive nausea/vomiting at Screening or an inability to swallow capsules.
- •Elevation of hepatic enzymes or renal compromise.
研究组 & 干预措施
RV521 Capsules
RV521 is formulated as a dry powder blend of RV521 drug substance with mannitol as excipient. They are a white, opaque capsule and administered orally.
干预措施: RV521 oral tablet (Drug)
RV521 Placebo Capsules
RV521 placebo capsules will contain mannitol and microcrystalline cellulose only. They are a white, opaque capsule and administered orally.
干预措施: Placebo oral tablet (Drug)
结局指标
主要结局
Change in RSV nasal viral load (via RT-qPCR)
时间窗: Pre-dose baseline (Day 1) through study completion; up to Visit 8 (Day 28)
RSV change measured by the time-weighted average (DAVG) viral load using RT qPCR
Proportion of subjects with a progression to Lower Respiratory Tract Complication (LRTC) during the study
时间窗: Pre-dose baseline (Day 1) through Visit 8 (Day 28)
Progression to LRTC during the study defined as one of the following: * Primary LRTI caused by RSV * Secondary bacterial LRTI * LRTI caused by another pathogen * LRTC of unknown etiology
次要结局
- Evaluate safety and tolerability of RV521 by assessing changes from baseline in pulse/heart rate (vital sign parameters)(Baseline through Visit 8 (Day 28))
- Proportion of subjects who require hospitalization during the study(Baseline (Day 1) through Visit 8 (Day 28))
- Mean number of days of hospitalization during the study(Baseline (Day 1) through Visit 8 (Day 28))
- Proportion of subjects requiring ICU(Baseline (Day 1) through Visit 8 (Day 28))
- Mean number of days in ICU(Baseline (Day 1) through Visit 8 (Day 28))
- Proportion of subjects requiring mechanical ventilation(Baseline (Day 1) through Visit 8 (Day 28))
- Number of subjects who experience death (all-cause mortality)(First dose of study drug through Visit 8 (Day 28))
- Number of subjects who experience death attributable to LRTC(First dose of study drug through Visit 8 (Day 28))
- Evaluate safety and tolerability of RV521 by assessing changes from baseline in systolic and diastolic BP (vital sign parameters)(Baseline through Visit 8 (Day 28))
- Evaluate safety and tolerability of RV521 by assessing changes from baseline in body temperature (vital sign parameters)(Baseline through Visit 8 (Day 28))
- Relationship between plasma exposures of RV521 and RSV viral loads measured in nasal swabs by RT-qPCR(Pre-dose baseline (Day 1) and every visit through Visit 8 (Day 28))
- Mean change in RSV viral load assessed via CBIA(Pre-dose baseline (Day 1) through study completion; up to Visit 8 (Day 28))
- Percent of participants who experience AEs, TEAEs, SAEs and withdrawals due to TEAEs(First dose of study drug through Visit 8 (Day 28))
- Evaluate safety and tolerability of RV521 by assessing changes from baseline in respiration rate (vital sign parameters)(Baseline through Visit 8 (Day 28))
- Evaluate safety and tolerability of RV521 by assessing changes from baseline weight/BMI(Baseline through Visit 8 (Day 28))
- Mean change from baseline in viral RNA shedding(Pre-dose baseline (Day 1) through study completion; up to Visit 8 (Day 28))
- Evaluate the proportion of subjects with changes in ECG measurements and changes in clinical impression from baseline(Measurements will be taken at Day 1/Visit 2 (pre-dose and at 5-hours post-dose), on Day 3/Visit 4 (at 5 hours post-dose), and at Visit 6 (Day 14))
- Relationship between plasma exposures of RV521 and RSV viral loads measured in nasal swabs by CBIA(Pre-dose baseline (Day 1) and every visit through Visit 8 (Day 28))
- Proportion of subjects who no longer shed RSV assessed by both RT-qPCR and CBIA at each timepoint(Pre-dose baseline (Day 1) through study completion; up to Visit 8 (Day 28))
- Evaluate the proportion of subjects with changes and shifts in hematology/clinical chemistry/urinalysis laboratory values (laboratory tests read by a central lab) from baseline.(Collected at Visit 2/Day 1 (pre-dose), Visit 4/Day 3, Visit 6/Day 14 and Visit 8/Day 28)
- Time to total resolution of all RSV-related symptoms(Daily from baseline (Day 1) through Visit 8 (Day 28))
- Proportion of days with lowest daily SpO2 ≥ 90% on room air(Daily from baseline (Day 1) through Visit 8 (Day 28))
- Time to improvement in RSV-related symptoms(Daily from baseline (Day 1) through Visit 8 (Day 28))
- Number of days where supplementary oxygen was required(Baseline (Day 1) through Visit 8 (Day 28))