Acute Respiratory Distress Syndrome Due to SARS-CoV-2 Infection (Severe COVID19)
Conditions
Brief summary
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.
Interventions
DRUGAMY-101
C3 complement inhibitor
OTHERWFI 5% glucose
Placebo
Sponsors
Amyndas Pharmaceuticals S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with Acute Respiratory Distress Syndrome due to SARS-CoV-2 infection (severe Covid-19), according to the following criteria: 1. Demonstration of SARS-CoV-2 RNAemia in nasopharyngeal swap or bronchio-alveolar lavage (BAL) 2. 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); 3. 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). | 21 days | — |
| The proportion of patients assigned to each category, of a six-category ordinal scale. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of respiratory failure-free survival | Day 44 | With respiratory failure defined as any of the following: 1. Worsening of severe gas transfer deficit, accounting for a shift in ARDS disease category (PaO2/FiO2 ≤200 for patients with PaO2/FiO2 \>200 at baseline; PaO2/FiO2 ≤100 for patients with PaO2/FiO2 \>100 at baseline), 2. Persistent respiratory distress while receiving oxygen (persistent marked dyspnea,use of accessory respiratory muscles, paradoxical respiratory movements), 3. Transfer to the intensive care unit for intubation, 4. Death. |
| Cumulative incidence of resolution of ARDS (defined as PaO2/FiO2 ≥200 in room air) | Through day 44 | — |
| Cumulative incidence of freedom from oxygen requirement | Through day 44 | — |
| Proportion of patients requiring invasive mechanical ventilation due to worsening of ARDS | Within 14 days after inclusion in the study | — |
| Proportion of patients requiring non-invasive mechanical ventilation (NIV) due to worsening of ARDS | Within 14 days after inclusion in the study | — |
| 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: Respiratory rate | Through day 44 | — |
| The proportion of patients assigned to each category, of a six-category ordinal scale. | On days 7, 14, and 44 | 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. |
| 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 | — |
| 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 | — |
| Changes in levels of AMY-101 plasma level | On days 1, 2, 4, 7, 10, 14, 15, 21 | — |
| Changes in maximal and minimal cardiovascular parameters: Heart Rate | Through day 44 | — |
| Proportion of patients surviving | Through to day 44 | — |
Outcome results
None listed