Efficacy and Safety of PUL-042 Inhalation Solution in Reducing Lower Respiratory Tract Complications in Patients With Hematologic Malignancies and Recipients of Hematopoietic Stem Cell Transplantation (HSCT) With Documented Viral Infections With PIV, hMPV or RSV
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 22
- 主要终点
- Efficacy of PUL-042 Inhalation Solution on Lower Respiratory Tract Complications (LRTC)
研究概览
简要总结
The purpose of this research study is to try to see whether an experimental drug, PUL 042 Inhalation Solution (PUL 042), is effective in reducing the severity of lung infections in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation with documented viral infections due to PIV, hMPV, or RSV. PUL-042 or a placebo will be administered 3 times over a 6-day period. The total duration of the study will be approximately 30 days.
详细描述
A total of up to 100 participants will be enrolled in this research study, at up to 15 centers. Participants in the study will receive either PUL-042 or a placebo (an inactive agent that appears identical to PUL-042). Patients will be randomized 1:1 for PUL-042 or placebo.
The first 50 patients will either be low dose PUL-042 or placebo. After review of the safety data from the initial patients, the PUL-042 dose may be increased. Subjects will be evaluated by chest x-ray and clinical status for respiratory complications.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Subjects will be eligible for entry into the study if a nasopharyngeal swab is positive for PIV, RSV, or hMPV (as a single pathogen or a mixed infection with rhinovirus) by molecular assay by a local laboratory AND subjects must fulfill the following inclusion criteria to be eligible for participation in the study:
- •Subjects with hematologic malignancies (i.e., leukemia, lymphoma, or multiple myeloma) or recipients of an allogeneic or autologous hematopoietic stem cell transplantation for one of the following diagnoses: leukemia, lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma, and myelodysplastic and myeloproliferative disorder.
- •Subjects who have undergone active cytotoxic chemotherapy within 6 months or subjects who are on an immunosuppressive therapy (e.g., alemtuzumab, ibrutinib, mycophenolate mofetil, corticosteroids ≥1mg/kg prednisone equivalent).
- •Subjects who are recipients of an allogeneic hematopoietic stem cell transplant (HSCT) must be deemed high risk with an Immunodeficiency Scoring Index (ISI) , of greater or equal to
- •Subjects who are recipients of an autologous HSCT must be within 3 months of the transplant procedure.
- •Subjects must be symptomatic with upper or lower respiratory tract symptoms such as rhinorrhea, sore throat or cough and must be dosed within 6 days from the onset of symptoms.
- •Chest X-ray with a Radiologic Severity Index (RSI) score of 6 or lower.
- •Subjects must have pulse oximetry of hemoglobin saturation ≥ 93% on room air.
- •Spirometry (forced expiratory volume in one second [FEV1] and forced vital capacity [FVC]) ≥70% of predicted value.
- •Adult (≥ 18 years of age).
- •If female, must be either post-menopausal (one year or greater without menses), surgically sterile, or, for female subjects of child-bearing potential who are capable of conception must be: practicing two effective methods of birth control (acceptable methods include intrauterine device, spermicide, barrier, male partner surgical sterilization, and hormonal contraception) during the study and through 30 days after completion of the study. Abstinence is not classified as an effective method of birth control.
- •If female, must not be pregnant, plan to become pregnant, or nurse a child during the study and through 30 days after completion of the study. A pregnancy test must be negative at the Screening Visit, prior to dosing on Day
- •If male, must be surgically sterile or willing to practice two effective methods of birth control (acceptable methods include barrier, spermicide, or female partner surgical sterilization) during the study and through 30 days after completion of the study. Abstinence is not classified as an effective method of birth control.
- •Ability to understand and give informed consent.
排除标准
- •Subjects will be excluded if they fulfill any of the following exclusion criteria:
- •Patients with a pulse oximetry of hemoglobin saturation less than 93% on room air.
- •Known history of chronic pulmonary disease (e.g., asthma [including atopic asthma, exercise-induced asthma, or asthma triggered by respiratory infection], chronic pulmonary disease, pulmonary fibrosis, COPD), pulmonary hypertension, or heart failure.
- •Subjects treated for fungal, viral, or bacterial pneumonia in the previous 30 days.
- •Exposure to any investigational agent (defined as any non-FDA-approved agent) within 30 days, or 5 half-lives of the investigational agent, whichever is longer, prior to the Screening Visit.
- •Allogeneic HSCT recipients with an ISI of 3 or less.
- •Autologous HSCT recipients more than 3 months after the transplant procedure.
- •Patients with a relapsed and/or refractory underlying hematologic malignancy with a life expectancy of less than 2 months.
- •HSCT recipients in the pre-engraftment period.
- •Chest X-ray with an RSI of >
- •Patients documented to be positive for other respiratory viruses (limited to influenza, SARS-CoV-2, adenovirus, or coronavirus) within 7 days prior to the Screening Visit, as determined by local testing (additional screening testing is not required).
- •Clinically significant bacteremia or fungemia within 7 days prior to the Screening Visit that has not been adequately treated, as determined by the Principal Investigator.
- •Any condition which, in the opinion of the Principal Investigator, would prevent full participation in this trial or would interfere with the evaluation of the trial endpoints.
- •Previous exposure to PUL-042 Inhalation Solution.
研究组 & 干预措施
PUL-042
PUL-042 Inhalation Solution
干预措施: PUL-042 (Drug)
Sterile Saline for Inhalation
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Efficacy of PUL-042 Inhalation Solution on Lower Respiratory Tract Complications (LRTC)
时间窗: 28 days
Determine efficacy of PUL-042 Inhalation Solution on lower respiratory tract complications (LRTC) using the peak post-treatment radiologic severity index (RSI) score in subjects with hematologic malignancies (HM \[lymphoma, multiple myeloma and leukemia\]) and hematopoietic stem cell transplant (HSCT) recipients with documented parainfluenza virus (PIV), human metapneumovirus (hMPV), or respiratory syncytial virus (RSV) infection. The RSI is a quantitative score based on the presence of pulmonary infiltrates in three zones in both lungs, a total of six zones. Normal in all zones would be a score of zero with a maximum score of 72, which represents total consolidation in all six zones.
次要结局
- Change from Pre-Treatment through 28 days(28 days)
- Post-Treatment Viral RNA Titers (copies/mL)(28 days)
- Duration of ICU Care (Days)(28 days)
- Adverse Events(28 days)
- Proportion of Subjects Positive for Each Virus at Each Sampling Timepoint(28 days)
- Oxygenation Requirements (Days)(28 days)
- Change in Viral RNA Shedding Relative to Baseline (copies/mL)(28 days)
- Respiratory Symptom Scores(28 days)
- Mortality (Incidence)(28 days)
- Incidence of ICU Admission(28 days)
- Duration of hospitalization (Days)(28 days)
- Incidence of Hospitalization(28 days)
- Incidence of Pneumonia (Clinical Diagnosis)(28 days)
- Dose/Response(28 days)
- Incidence of Hospitalization(28 days)
- Respiratory Symptom Scores(28 days)
- Incidence of Pneumonia (Clinical Diagnosis)(28 days)
- Change from Pre-Treatment through 28 days(28 days)
- Proportion of Subjects Positive for Each Virus at Each Sampling Timepoint(28 days)
- Change in Viral RNA Shedding Relative to Baseline (copies/mL)(28 days)
- Post-Treatment Viral RNA Titers (copies/mL)(28 days)
- Mortality (Incidence)(28 days)
- Oxygenation Requirements (Days)(28 days)
- Duration of ICU Care (Days)(28 days)
- Incidence of ICU Admission(28 days)
- Duration of hospitalization (Days)(28 days)
- Dose/Response(28 days)