A Study of the C3 Inhibitor AMY-101 in Patients With ARDS Due to COVID-19 (SAVE)

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Acute Respiratory Distress Syndrome Due to SARS-CoV-2 Infection (Severe COVID19)

Intervention / Treatment
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* Drug: AMY-101
* Other: WFI 5% glucose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMY-101<br> | Drug: AMY-101<br>* C3 complement inhibitor<br>|
| Placebo Comparator: Placebo<br> | Other: WFI 5% glucose<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients assigned to each category, of a six-category ordinal scale. | 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. | On days 7, 14, and 44 | 
| Proportion of patients surviving |  | Through to day 44 | 
| Proportion of respiratory failure-free survival | With respiratory failure defined as any of the following: 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), Persistent respiratory distress while receiving oxygen (persistent marked dyspnea,use of accessory respiratory muscles, paradoxical respiratory movements), Transfer to the intensive care unit for intubation, Death. | Day 44 | 
| 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 | 
| 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 | 
| 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 |