Multicenter, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study of LSALT Peptide as Prevention of Acute Respiratory Distress Syndrome (ARDS) and Acute Kidney Injury in Patients Infected With SARS-CoV-2 (COVID-19)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 7
- 主要终点
- To Evaluate the Proportion of Subjects Alive and Free of Respiratory Failure and Free of the Need for Continued Renal Replacement Therapy (RRT) on Day 28 (as Per Protocol AB002 - Version 1, Dated 09JUNE2020)
研究概览
简要总结
To evaluate the proportion of subjects alive and free of respiratory failure (e.g. need for non-invasive or invasive mechanical ventilation, high flow oxygen, or ECMO) and free of the need for continued renal replacement therapy (RRT) on Day 28. The need for continued RRT at Day 28 will be defined as either dialysis in the past 3 days (Day 26, 27, or 28) or an eGFR on Day 28 <10 mL/min/1.73 m2.
详细描述
This study is a parallel group, randomized, third-party blinded, multicenter study to assess safety and efficacy of LSALT peptide versus placebo in hospitalized patients with confirmed infection or recent confirmed infection with complications associated with COVID-19. Following screening and after establishing baseline parameters such as lung and renal function, clinical chemistries, coagulation, hematology, and urinalysis, and satisfying all inclusion and exclusion criteria, patients will be randomized to one of two blinded treatment regimens:
- 100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily
- 100 mL drug-free IV saline infusion over 2 hours daily.
Thirty (30) patients will be randomized to active drug (LSALT peptide) and 30 patients will be randomized to matching placebo. This study will be third-party blind with only the Pharmacist at the site unblinded for the purpose of preparing drug/placebo for injection.
Patients will be followed for safety and efficacy up to Day 28, with Day 1 being the day of randomization to assess safety. After assessing the risk of ARDS and satisfying all inclusion and exclusion criteria, the patient will be randomized to 5 mg LSALT peptide or blinded placebo to be given intravenously once daily for a maximum of 14 days. Physical and respiratory examinations, vital signs, and adverse events will be recorded throughout the study, including Day 28 (EOS). Blood chemistries, hematology, coagulation, urinalysis, ECG, SARS-CoV-2 tests, eGFR, and chest x-ray (CXR) will be assessed at Day 1 (Screening/Baseline) prior to initiation of study drug, and on Day 3, EOT, and at EOS, as well as when clinically indicated. The ECG at EOS will only be obtained if clinically indicated. An additional CXR will be obtained at time of clinical improvement. Cytokines/biomarkers and pharmacokinetics (PK) will be assessed at Day 1 (Screening/Baseline) prior to initiation of study drug, at 1 (mid-dose) and 2 hours (end of infusion) of drug therapy on Days 1, 3, EOT, and a single blood sample at EOS for cytokines/biomarkers only. Where applicable, a urinary pregnancy test will be obtained at Screening in women of childbearing potential. Questionnaires (APACHE II, SOFA) will be obtained at Baseline, Day 3, EOT, and EOS; venous blood gas (VBG) or HCO3 (bicarbonate) levels may be substituted for arterial blood gas (ABG) if it is considered standard-of-care (SOC) or in the patient's best interest, and results in comparable APACHE II and SOFA scores. Other questionnaires (Berlin Definition and modified Medical Research Council Dyspnea Scale) will be assessed at Baseline, Day 3, EOT, and EOS. IgG, IgA, and IgM antiviral antibodies will be collected at Baseline and EOS. Patients will be maintained on the SOC per institutional guidelines, including prophylaxis or treatment of VTE, throughout the study.
A Data and Safety Monitoring Board (DSMB) will evaluate patients on a continuing basis for primarily safety assessments. Per the DSMB Charter, the DSMB will meet at least monthly if not more frequently based upon enrollment throughout the study period.
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
- 未提供
排除标准
- •Known sensitivity, allergy, or previous exposure to LSALT peptide.
- •Exposure to any investigational drug or device <90 days prior to entry into study.
- •Treatment with immunomodulators or immunosuppressant drugs, including but not limited to IL-6 inhibitors, TNF inhibitors, anti-IL-1 immunomodulators, and JAK inhibitors within five half-lives or 30 days (whichever is longer) prior to randomization and throughout the study period. However, should any of these treatments become standard-of-care and incorporated into clinical treatment guidelines (e.g. those of WHO or NIH), the treatment is permitted. Further, low-dose oral prednisone (<20 mg/day) and inhaled steroids (e.g. treatment of asthma) are allowed in the study.
- •Anticipated transfer to another hospital or medical center within 72 hours, which is not a study site.
- •Uncontrolled of poorly treated active hepatitis B (HBV), hepatitis C (HepC), or HIV infection. Those subjects who are positive for HBV, HepC, or HIV but are well-controlled with low viral loads are allowed to participate in this study:
- •HBV low viral load defined as <20,000 IU/mL
- •HepC low viral load defined as <800,000 IU/mL
- •HIV low viral load defined as <5000 copies/mL
- •Participation in another drug or device study at any time during this study, for example:
- •Ulinastatin 200,000 IU or greater
- •High dose intravenous Vitamin C
- •Budesonide and formoterol
- •Bevacizumab to prevent ARDS
- •Dornase alfa to reduce hypoxemia in ventilated trauma patients.
- •As indicated in the inclusion criteria, pregnant female patients are excluded from study. Further, female patients who are nursing are excluded from study.
- •Has any medical condition considered to be clinically significant and could potentially affect patient safety or study outcome, including but not limited to:
- •Acute or chronic kidney disease (stage-4 or -5 renal impairment; eGFR<30 mL/min/1.73 m2 or hemodialysis)
- •End-stage malignancy undergoing treatment
- •Immunocompromised patients or those with medical/surgical conditions (e.g., solid organ transplantation) which require chronic immunosuppression
- •Chronic hematologic disease which, in the opinion of the PI, prohibits the patient from entering into study
- •Acute liver injury with AST and/or ALT levels greater than 3x ULN unless recent injury (within 2 weeks) likely due to COVID-19 infection
- •History of coagulopathy within the last year as defined by abnormal ACT, aPTT, and/or PT/INR values at least 2-fold outside normal limits, and currently present at screening, and/or
- •End-stage lung disease, acute lung injury, severe chronic obstructive pulmonary disease (COPD) as assessed by the GOLD criteria (GOLD Stage IV), or mechanical ventilation.
研究组 & 干预措施
Placebo
100 mL drug-free IV saline infusion over 2 hours daily
干预措施: Placebo (Drug)
LSALT
100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily
干预措施: LSALT peptide (Drug)
结局指标
主要结局
To Evaluate the Proportion of Subjects Alive and Free of Respiratory Failure and Free of the Need for Continued Renal Replacement Therapy (RRT) on Day 28 (as Per Protocol AB002 - Version 1, Dated 09JUNE2020)
时间窗: 28 days
Respiratory failure is defined as the need for non-invasive or invasive mechanical ventilation, high flow oxygen \[≥ 6 L/minute\], or ECMO. The need for continued RRT at Day 28 will be defined as either dialysis in the past 3 days (Day 26, 27, or 28) or an eGFR on Day 28 \<10 mL/min/1.73 m2.
次要结局
- All-cause Mortality(28 days)
- The Presence of and Severity of ARDS as an Ordinal Outcome of the Proportion of Patients Who Have None, Mild, Moderate, or Severe ARDS(28 days)
- Time to Each of Mild, Moderate, or Severe ARDS(28 days)
- The Number of Ventilation-free Days(28 days)
- Time on Nasal Cannula or Oxygen Mask(28 days)
- Length of Stay in ICU and Hospital (Admission to Discharge)(28 days)
- Virologic Clearance Rate(28 days)
- Worst PaO2/FiO2 Ratio Following Enrollment(28 days)
- Change in PaO2/FiO2 Ratio(28 days)
- Change in Baseline Modified Medical Research Council (mMRC) Score(28 days)
- Change in Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II Score(28 days)
- Change in Daily Sequential Organ Failure Assessment (SOFA) Score From Baseline in Patients With Extrapulmonary Organ Dysfunction(28 days)
- Change in Liver Function by Alanine Aminotransferase (ALT) Test(28 days)
- Change in Liver Function by Aspartate Transferase (AST) Test(28 days)
- Change in Liver Function by Total Bilirubin Test(28 days)
- Change in Renal Function by Serum Creatinine (SCr) Test(28 days)
- Change in Activated Coagulation Time (ACT)(28 days)
- Change in Activated Partial Thromboplastin Time (aPTT)(28 days)
- Change in Prothrombin International Normalized Ratio (INR)(28 days)
- Vasopressor-free Days(28 days)
- Change From Maximal Radiographic Damage to EOT(28 days)
- Change in Renal Function by Estimated Glomerular Filtration Rate (eGFR) Test(28 days)
- Change in Hs-troponin Levels(28 days)
- Change in Antiviral IgG, IgA, and IgM Levels(28 days)