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

Amyndas Pharmaceuticals S.A.144 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

144

Conditions

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

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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).

Time frame: 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.

Time frame: 21 days

Secondary Outcomes

The proportion of patients assigned to each category, of a six-category ordinal scale.

Time frame: On days 7, 14, and 44

Proportion of patients surviving

Time frame: Through to day 44

Proportion of respiratory failure-free survival

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.

Time frame: Day 44

Cumulative incidence of resolution of ARDS (defined as PaO2/FiO2 ≥200 in room air)

Time frame: Through day 44

Cumulative incidence of freedom from oxygen requirement

Time frame: Through day 44

Proportion of patients requiring invasive mechanical ventilation due to worsening of ARDS

Time frame: Within 14 days after inclusion in the study

Proportion of patients requiring non-invasive mechanical ventilation (NIV) due to worsening of ARDS

Time frame: Within 14 days after inclusion in the study

Proportion of patients developing thrombotic microangiopathies

Time frame: Through day 44

Changes in PaO2 and PaO2/FIO2

Time frame: Through day 44

Changes in quick Sequential Organ Failure Assessment Score (qSOFA: respiratory rate, systolic blood pressure, Glasgow Coma Scale (GCS)

Time frame: Through day 44

Changes in maximal and minimal cardiovascular parameters: Respiratory rate

Time frame: Through day 44

Changes in maximal and minimal cardiovascular parameters: Heart Rate

Time frame: Through day 44

Changes in levels of biomarkers of inflammation (CBC, CRP, Ferritin, Procalcitonin, D-dimers, LDH)

Time frame: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44

Length of stay in ICU

Time frame: Through day 44

Cumulative incidence of discharge from hospital

Time frame: Through day 44

Number of adverse events

Time frame: Through day 44

Changes in levels of anti-drug antibodies

Time frame: On day 0 , 14 and 44

Changes in levels of biomarkers of complement activity: C3, C3a, C5a, sC5b-9

Time frame: 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

Time frame: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44

Changes in levels of Club Cell protein CC16 (biomarker of lung damage )

Time frame: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44

Changes in levels of AMY-101 plasma level

Time frame: On days 1, 2, 4, 7, 10, 14, 15, 21