A Phase 2, Randomized, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of Brilacidin in Hospitalized Participants With COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Time to Sustained Recovery Through Day 29
研究概览
简要总结
The study assessed the efficacy and safety of Brilacidin for the treatment of COVID-19 in hospitalized participants
详细描述
This Phase 2 study was a randomized, blinded, placebo-controlled, parallel group design.
The target population treated were patients with moderate to severe COVID-19, active SARS-CoV-2 infection confirmed by positive standard polymerase chain reaction (PCR) test (or equivalent/ other approved diagnostic test) within 4 days prior to starting study treatment, and were hospitalized with respiratory distress but not yet requiring high-level respiratory support (as defined in exclusion criterion #2). See inclusion/exclusion criteria.
For each participant, the study was comprised of three parts:
- Screening/ Baseline visit (Day -1 to 1): Lasting up to 24-48 hours and comprised screening/ baseline assessments. This visit was to confirm that study inclusion and exclusion criteria were met by participants prior to randomization.
- Treatment period (Day 1-3 or Day 1-5): Randomized subjects received blinded study treatment once daily for 3 or 5 days by IV infusion, in addition to Standard of Care (SoC).
- Follow-up period (Day 4 or 6 through Day 60): Subjects were assessed daily while hospitalized. Discharged patients were asked to attend study visits at Days 15 and 29. A follow-up visit at Day 60(±10), by telephone call, was performed to confirm patient status.
All participants had a series of efficacy and safety assessments performed, including laboratory assays. Additional blood samples and nasopharyngeal (NP) swabs were also obtained (oropharyngeal (OP) swabs were to be collected only in exceptional circumstances).
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)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed and dated written Informed Consent Form (ICF) to participate in the clinical study by patient capable of giving consent, or, when the patient is not capable of giving consent, by his or her legal/authorized representative.
- •Male or non-pregnant female adults between 18 and 80 years of age, inclusive, at time of informed consent.
- •SARS-CoV-2 infection confirmed by positive standard polymerase chain reaction (PCR) test (or equivalent/ other approved diagnostic test) ≤ 4 days before randomization.
- •Currently hospitalized and requiring medical care for COVID-
- •Moderate OR severe COVID-19, defined by respiratory function at screening, as below:
- •Moderate, meets at least one of the following criteria:
- •Peripheral oxygen saturation SpO2 > 93% on room air;
- •Respiratory rate ≥ 20 to < 30 breaths per minute.
- •Severe, meets at least one of the following criteria:
- •Peripheral oxygen saturation SpO2 ≤ 93% on room air OR arterial oxygen partial pressure (PaO2) / fraction of inspired oxygen (FiO2) < 300mmHg (1mmHg=0.133kPa) [corrective formulation should be used for higher altitude regions (over 1000m)];
- •Respiratory rate ≥ 30 breaths per minute.
- •Body mass index (BMI) of ≥18 to <40kg/m2 at screening.
- •Agrees to the collection of nasopharyngeal (NP) swabs and venous blood per protocol.
- •In the opinion of the investigator, willing and able to comply with the study protocol assessments, and is committed to the study and the study follow up visits.
排除标准
- •Participation in any other clinical trial of an experimental agent treatment.
- •Requiring invasive mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) at the time of randomization.
- •Has explicitly expressed the wish not to receive intensive care support (Do not resuscitate or Do not intubate order) should this become necessary.
- •In the opinion of the investigator, progression to death is imminent and inevitable within the next 72 hours, irrespective of the provision of treatment, such as rapidly progressive multiorgan failure.
- •Requiring systemic anti-infective therapy for suspected or confirmed active bacterial/fungal/viral systemic infection other than COVID-
- •Hypertensive urgency (e.g., SBP >220 mmHg or DBP >120 mmHg) or hypertensive emergency within the last 72 hours, as assessed by the investigator following local guidelines.
- •If has a history of hypertension in the last 3 months, must have been receiving appropriate anti-hypertensive therapy in accordance with local guidelines.
- •Evidence of moderate or severe hepatic impairment (Child-Pugh Class B or C).
- •Estimated GFR (eGFR) <30 mL/min/1.73m2 (based on CKD-EPI formula).
- •Prior to a participant's study entry, known allergies or intolerance to Brilacidin or formulation excipients.
- •Any serious medical or psychiatric condition or test abnormality(ies) that, in the investigator's judgment, puts the participant at significant risk, could confound the study results, or may interfere significantly with the subject's safe participation in and completion of the study.
- •Pregnancy or breast-feeding, or positive urine or serum pregnancy test in a pre-dose assessment.
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception throughout the study and for up to 30 days after stopping treatment.
- •Sexually active males with female partners of childbearing potential unwilling to use a condom when engaging in intercourse of reproductive potential throughout the study and for up to 30 days after stopping treatment.
研究组 & 干预措施
Brilacidin + SoC
Brilacidin IV infusion, 3 days and up to 5 days, in addition to Standard of Care
干预措施: Brilacidin (Drug)
Brilacidin + SoC
Brilacidin IV infusion, 3 days and up to 5 days, in addition to Standard of Care
干预措施: Standard of Care (SoC) (Drug)
Placebo + SoC
Placebo IV infusion, 3 days and up to 5 days, in addition to Standard of Care
干预措施: Placebo (Drug)
Placebo + SoC
Placebo IV infusion, 3 days and up to 5 days, in addition to Standard of Care
干预措施: Standard of Care (SoC) (Drug)
结局指标
主要结局
Time to Sustained Recovery Through Day 29
时间窗: Day 1 through Day 29
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the clinical status ordinal scale with response sustained through Day 29: 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care (other than for per protocol dosing or assessments, as appropriate); 7. Not hospitalized, limitation on activities and/or requiring home oxygen; 8. Not hospitalized, no limitations on activities
Percentage of Participants With Sustained Recovery Through Day 29
时间窗: Day 5, Day 8, Day 11, Day 15, Day 29
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the clinical status ordinal scale with response sustained through Day 29: 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care (other than for per protocol dosing or assessments, as appropriate); 7. Not hospitalized, limitation on activities and/or requiring home oxygen; 8. Not hospitalized, no limitations on activities
次要结局
- Time to at Least Two Category Improvement in Clinical Status(Day 1 through Day 29)
- Subject Clinical Status(Day 1, Day 8, Day 15, Day 29)
- Number and Percentage of Participants Achieving Recovery Status Scores at Day 29(Day 29)
- Number and Percentage of Participants Who Die or Develop Respiratory Failure by Day 29(Day 1 through Day 29)
- Number and Percentage of Participants Achieving at Least One Category Improvement in Clinical Status(Day 8, Day 15, Day 29)
- Number and Percentage of Participants Achieving at Least Two Category Improvement in Clinical Status(Day 8, Day 15, Day 29)
- Number and Percentage of Participants With Treatment-Emergent Adverse Events(Day 1 through Day 60)
- Number and Percentage of Participants With Treatment-Emergent Adverse Events of Special Interest(Day 1 through Day 60)
- Time to at Least One Category Improvement in Clinical Status(Day 1 through Day 29)
- Time to a National Early Warning Score 2 (NEWS2) of <= 2 Maintained for 24 Hours(Day 1 through Day 29)
- Percentage of Participants Achieving a National Early Warning Score 2 (NEWS2) of <= 2 Maintained for 24 Hours(Day 5, Day 8, Day 11, Day 15)
- Change From Baseline in National Early Warning Score 2 (NEWS2)(Day 1 through Day 29)