A Phase 2 Clinical Trial to Assess the Safety and Efficacy of Complement 3 Inhibitor, AMY-101, in Patients With Acute Respiratory Distress Syndrome Due to COVID-19 (SAVE)
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 144
- 主要终点
- The proportion of patients who are alive, without evidence of ARDS (i.e. PaO2/FIO2 >300 mm Hg), who do not require any oxygen support (in room air).
研究概览
简要总结
The study is a prospective, randomized, placebo-controlled, single-blind phase 2 clinical study of the efficacy and safety of AMY-101, a potent C3 inhibitor, for the management of patients with ARDS caused by SARS-CoV-2 infection.
We will assess the efficacy and safety, as well as pharmacokinetics (PK), and pharmacodynamics (PD). The study will assess the impact of AMY-101 in patients with severe COVID19; specifically, it will assess the impact of AMY-101 1) on survival without ARDS and without oxygen requirement at day 21 and 2) on the clinical status of the patients at day 21.
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
- Single (Participant)
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
- •Diagnosed with Acute Respiratory Distress Syndrome due to SARS-CoV-2 infection (severe Covid-19), according to the following criteria:
- •Demonstration of SARS-CoV-2 RNAemia in nasopharyngeal swap or bronchio-alveolar lavage (BAL)
- •A ratio of the partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2), PaO2/FIO2, ≤300 mmHg
- •Mild ARDS (PaO2/FIO2, ≤300 and >200 mm Hg);
- •Moderate ARDS (PaO2/FIO2, ≤200 and >100 mm Hg);
- •Severe ARDS (PaO2/FIO2, ≤100 mm Hg);
- •Pulmonary infiltrates suggestive of SARS-COV-2-related ARDS: e.g., bilateral infiltrates at chest X-ray or B-lines at lung US scan.
- •Dated and signed informed consent from patient or legal represantative.
排除标准
- •Intubated patients
- •Demonstrated or suspected uncontrolled systemic severe infection, such as sepsis (e.g.: positive blood culture, or procalcitonin ≥0.25 µg/L)
- •Demonstrated local extrapulmonary abscess
- •ARDS due to cardiac failure or fluid overload
- •Concomitant treatment with immunomodulatory /immunosuppressive drugs , which have potential activity against the disease
- •Multi Organ Failure (MOF)
- •Severe renal failure (CKD, by defition glomerular filtration rate <30 ml/min)
- •Neisseria meningitidis infection that is not resolved
- •Current treatment with a complement inhibitor
- •Intravenous immunoglobulin (IVIg) within 3 weeks prior to Screening
- •Participation in another interventional treatment study within 30 days before initiation of the study treatment (Day 1 in this study) or within 5 half-lives of that investigational product, whichever is greater.
- •Chemotherapy for less than 3months
- •Pregnancy
- •Age <18.
研究组 & 干预措施
AMY-101
干预措施: AMY-101 (Drug)
Placebo
干预措施: WFI 5% glucose (Other)
结局指标
主要结局
The proportion of patients who are alive, without evidence of ARDS (i.e. PaO2/FIO2 >300 mm Hg), who do not require any oxygen support (in room air).
时间窗: 21 days
The proportion of patients assigned to each category, of a six-category ordinal scale.
时间窗: 21 days
The clinical status is based on the following six-category ordinal scale: * 1: not hospitalised; * 2: hospitalised, not requiring supplemental oxygen; * 3: hospitalised, requiring supplemental oxygen; * 4: hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both; * 5: hospitalised, requiring ECMO, invasive mechanical ventilation, or both; and * 6: death.
次要结局
- Changes in maximal and minimal cardiovascular parameters: Respiratory rate(Through day 44)
- Proportion of respiratory failure-free survival(Day 44)
- Cumulative incidence of freedom from oxygen requirement(Through day 44)
- Proportion of patients developing thrombotic microangiopathies(Through day 44)
- Changes in PaO2 and PaO2/FIO2(Through day 44)
- Changes in quick Sequential Organ Failure Assessment Score (qSOFA: respiratory rate, systolic blood pressure, Glasgow Coma Scale (GCS)(Through day 44)
- Changes in maximal and minimal cardiovascular parameters: Heart Rate(Through day 44)
- Changes in levels of biomarkers of inflammation (CBC, CRP, Ferritin, Procalcitonin, D-dimers, LDH)(On days 0, 1, 2, 4, 7, 10, 14, 21 and 44)
- Length of stay in ICU(Through day 44)
- Cumulative incidence of discharge from hospital(Through day 44)
- Number of adverse events(Through day 44)
- Changes in levels of anti-drug antibodies(On day 0 , 14 and 44)
- Changes in levels of biomarkers of complement activity: C3, C3a, C5a, sC5b-9(On days 0, 1, 2, 4, 7, 10, 14, 21 and 44)
- Proportion of patients surviving(Through to day 44)
- The proportion of patients assigned to each category, of a six-category ordinal scale.(On days 7, 14, and 44)
- Cumulative incidence of resolution of ARDS (defined as PaO2/FiO2 ≥200 in room air)(Through day 44)
- Proportion of patients requiring invasive mechanical ventilation due to worsening of ARDS(Within 14 days after inclusion in the study)
- Changes in levels of AMY-101 plasma level(On days 1, 2, 4, 7, 10, 14, 15, 21)
- Proportion of patients requiring non-invasive mechanical ventilation (NIV) due to worsening of ARDS(Within 14 days after inclusion in the study)
- Changes in levels of biomarkers of cytokine release syndrome: IL-1, IL-6, IL-12(On days 0, 1, 2, 4, 7, 10, 14, 21 and 44)
- Changes in levels of Club Cell protein CC16 (biomarker of lung damage )(On days 0, 1, 2, 4, 7, 10, 14, 21 and 44)