Phase 2 Clinical Platform Trial Investigating Multiple Therapeutic Options for the Treatment of Hospitalized Patients With Acute Respiratory Distress Syndrome (ARDS)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 64
- 主要终点
- All-cause mortality (ACM) rate at Day 28
研究概览
简要总结
This is a Phase 2 multicenter, randomized, double-blinded, placebo-controlled study that will evaluate the safety and efficacy of host-directed therapeutics in hospitalized adults diagnosed with Acute Respiratory Distress Syndrome (ARDS) utilizing a platform trial design.
Cohort C: Participants will be randomized to receive either a placebo or bevacizumab.
This record describes the default procedures and analyses for Cohort C. Please see NCT06703073 for information on the BP-ARDS-P2-001 Master Protocol.
详细描述
This is a master protocol for a Phase 2 platform clinical trial to evaluate host-directed therapeutic candidates (i.e., investigational product, IP) for the treatment of hospitalized participants diagnosed with ARDS. The safety and efficacy of each IP will be studied within its own cohort (IP versus Placebo). All patients will continue to receive standard treatments for ARDS as per the investigator. An individual participant will complete the study in approximately 90 days. The study will include a screening period (<24 hours from providing informed consent to treatment), in-hospital treatment period with IP/placebo starting on Day 1 through discharge from the hospital, and a follow-up period after discharge from the hospital through the end of study (Day 90 + 2 weeks). Outcome data will be assembled for each patient over time (such as ventilatory status, oxygenation, and survival). Functional status using the WHO Ordinal scale and Karnofsky scale will be collected. Resource utilization will be calculated (length of stay in a critical care setting, days intubated, and survival).
All participants will undergo a series of physical exams, laboratory assessments/biomarker collections, ECG, Chest X-ray or CT scan, and questionnaires through Day 90. Exploratory biomarkers will be evaluated over time to facilitate clinical learning. This record only includes information relevant to the bevacizumab cohort.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
The overall 2-step randomization scheme will be implemented.
- Randomization Level 1 will be open-label, assigning an eligible patient to one of the available treatment cohorts.
- Randomization Level 2 will be double-blinded and will randomize participants at a 1:1 ratio to receive either IP or placebo within a specific cohort. Thus, the PPD blinded team, site blinded staff members, and participants/legal authorized representative will be considered blinded to study treatment assignment (either IP or placebo) throughout the course of the study.
To preserve the integrity of the study blind, an unblinded pharmacist at each site will be responsible for the reconstitution and dispensation of all study drugs and placebos and will endeavor to ensure that there are no observable differences between the treatment groups (IP or placebo) when dispensing the study materials.
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
- •The following inclusion criteria are in addition to the
排除标准
- •specified in the Master Protocol NCT
- •ARDS Severity of mild, moderate or severe, based on PaO2/FiO2 or SpO2/FiO2 assessment at the time of randomization.
- •Exclusion Criteria:
- •The following exclusion criteria are in addition to the exclusion criteria specified in the Master Protocol NCT
- •Participant has a known allergy or hypersensitivity to the active substance/excipients, or Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies
- •Participant with established cirrhosis and a modified Child-Pugh Score of 7 or greater
- •Participant was dialysis-dependent prior to hospitalization. Participant must have a urine dipstick for proteinuria < 2+
- •The hospitalized participant has a history or currently experiencing the following:
- •Participant must not have an international normalized ratio (INR) >1.5 and/or aPTT >1.5 × upper limit of normal (ULN) within 7 days prior to initiation of study treatment for participants not receiving anticoagulation. For participants on full dose oral or parenteral anticoagulants for therapeutic purposes the INR and/or activated partial thromboplastin time (aPTT) must be within therapeutic limits (according to institution standards) within 7 days prior to initiation of study treatment and the participant on a stable dose of anticoagulants for ≥ 2 weeks prior to initiation of study treatment.
- •Participant with recent serious hemorrhage or history of recent hemoptysis > 2 episodes (defined as ≥2.5 mL of bright red blood per episode) within 1 month of screening.
- •Participant with inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg). Antihypertensive therapy is permitted to achieve these parameters.
- •Participant with a history of hypertensive crisis or hypertensive encephalopathy.
- •Participant with a history of Grade ≥ 4 venous thromboembolisms.
- •Participant with significant vascular disease (eg, aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 3 months of study drug treatment.
- •Participant with history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or active gastrointestinal bleeding within 6 months of study drug treatment.
- •Participant with serious, non-healing wound, active ulcer, or untreated bone fracture.
- •Participant with history or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (ie, in the absence of therapeutic anticoagulation).
- •Participant with clinically significant cardiovascular disease including cerebrovascular accident or myocardial infarction within previous 6 months, unstable angina, congestive heart failure, or serious cardiac arrhythmia uncontrolled by medication.
- •Participant with a platelet count of <75×109/L.
- •Participant with current or recent (<10 days prior to initiation of study treatment) use of aspirin (>325 mg/day) or clopidogrel (>75 mg/day).
- •Participant is receiving a direct anticoagulant (DOAC) such as dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) without the availability of a reversal agent at the site.
- •Participant is receiving a DOAC such as betrixaban (Bevyxxa®) and edoxaban (Lixiana®) for which there is no approved reversal agent.
- •Participant has urine dipstick for proteinuria ≥ 2+
研究组 & 干预措施
Cohort C: bevacizumab
干预措施: Cohort C: bevacizumab (Drug)
Cohort C: placebo
干预措施: Cohort C: placebo (Drug)
结局指标
主要结局
All-cause mortality (ACM) rate at Day 28
时间窗: Day 28
次要结局
- ACM at Day 60 and Day 90(Day 60 and Day 90)
- Ventilator-free days up to and including Day 28(Up to and including Day 28)
- Improvements in oxygenation measured as change from baseline in PaO2/FiO2 ratio up to and including Day 28 (or discharge, whichever is earlier)(Up to and including Day 28 or until Discharge (whichever is earlier))
- Incidence of new invasive mechanical ventilation use during the study up to and including Day 28(Up to and including Day 28)
- Proportion of participants alive and free of mechanical ventilation at Days 28, 60, and 90(Days 28, 60, and 90)
- Time to recover gas exchange to a PaO2/FiO2 ≥ 300 measured on 2 consecutive days during the first 28 days after informed consent(Up to and including Day 28)
- Extracorporeal Membrane Oxygenation (ECMO) free days up to and including Day 28(up to and including Day 28)
- Incidence of participants with new ECMO use during the study up to and including Day 28.(up to and including Day 28)
- Proportion of participants alive and free of ECMO at Days 28, 60, and 90(Days 28, 60, and 90)
- Proportion of participants achieving a ≥2-point improvement from baseline in the World Health Organization (WHO) 8-levels ordinal scale (from 0-8)(While Hospitalized (up to 90 days))
- Time to an improvement of one category and two categories from baseline using the WHO 8-levels ordinal scale (from 0-8) at Days 28, 60, and 90 (while hospitalized)(While Hospitalized (up to 90 days))
- Mean change in the WHO 8-levels ordinal scale from baseline through Day 90 (while hospitalized)(While Hospitalized (up to 90 days))
- Proportion of participants who improve clinical status as measured by the Karnofsky scale(Post hospitalization through Day 90)
- Change in Short Form Health Survey (SF-12) from hospital discharge to Day 60 and to Day 90(from hospital discharge to Day 60 and to Day 90from hospital discharge to Day 60 and to Day 90)
- Change in St. George's Respiratory Questionnaire (SGRQ) from hospital discharge to Day 60 and to Day 90(From hospital discharge to Day 60 and to Day 90)
- Days of hospitalization up to and including Day 28(up to and including Day 28)
- Days of ICU stay up to and including Day 28(up to and including Day 28)
- Incidence and severity of adverse events (AEs) /adverse event of special interest (AESI) / serious adverse event (SAEs)(Through Day 90)
- ACM+ at Day 28, Day 60, and Day 90(Time Frame: Day 28, Day 60, and Day 90)