Acute Respiratory Distress Syndrome Due to SARS-CoV-2 Infection (Severe COVID19) Clinical Trial
— SAVEOfficial title:
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)
| Verified date | February 2021 |
| Source | Amyndas Pharmaceuticals S.A. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Not yet recruiting |
| Enrollment | 144 |
| Est. completion date | December 2022 |
| Est. primary completion date | September 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| n/a | |||
| Lead Sponsor | Collaborator |
|---|---|
| Amyndas Pharmaceuticals S.A. |
Mastaglio S, Ruggeri A, Risitano AM, Angelillo P, Yancopoulou D, Mastellos DC, Huber-Lang M, Piemontese S, Assanelli A, Garlanda C, Lambris JD, Ciceri F. The first case of COVID-19 treated with the complement C3 inhibitor AMY-101. Clin Immunol. 2020 Jun;215:108450. doi: 10.1016/j.clim.2020.108450. Epub 2020 Apr 29. — View Citation
Risitano AM, Mastellos DC, Huber-Lang M, Yancopoulou D, Garlanda C, Ciceri F, Lambris JD. Complement as a target in COVID-19? Nat Rev Immunol. 2020 Jun;20(6):343-344. doi: 10.1038/s41577-020-0320-7. Epub 2020 Apr 23. Erratum in: Nat Rev Immunol. 2020 Jul;20(7):448. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | ||
| Primary | 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 | 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 | |
| Secondary | Proportion of patients surviving | Through to day 44 | ||
| Secondary | 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 | |
| Secondary | Cumulative incidence of resolution of ARDS (defined as PaO2/FiO2 =200 in room air) | Through day 44 | ||
| Secondary | Cumulative incidence of freedom from oxygen requirement | Through day 44 | ||
| Secondary | Proportion of patients requiring invasive mechanical ventilation due to worsening of ARDS | Within 14 days after inclusion in the study | ||
| Secondary | Proportion of patients requiring non-invasive mechanical ventilation (NIV) due to worsening of ARDS | Within 14 days after inclusion in the study | ||
| Secondary | Proportion of patients developing thrombotic microangiopathies | Through day 44 | ||
| Secondary | Changes in PaO2 and PaO2/FIO2 | Through day 44 | ||
| Secondary | Changes in quick Sequential Organ Failure Assessment Score (qSOFA: respiratory rate, systolic blood pressure, Glasgow Coma Scale (GCS) | Through day 44 | ||
| Secondary | Changes in maximal and minimal cardiovascular parameters: Respiratory rate | Through day 44 | ||
| Secondary | Changes in maximal and minimal cardiovascular parameters: Heart Rate | Through day 44 | ||
| Secondary | 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 | ||
| Secondary | Length of stay in ICU | Through day 44 | ||
| Secondary | Cumulative incidence of discharge from hospital | Through day 44 | ||
| Secondary | Number of adverse events | Through day 44 | ||
| Secondary | Changes in levels of anti-drug antibodies | On day 0 , 14 and 44 | ||
| Secondary | 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 | ||
| Secondary | 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 | ||
| Secondary | Changes in levels of Club Cell protein CC16 (biomarker of lung damage ) | On days 0, 1, 2, 4, 7, 10, 14, 21 and 44 | ||
| Secondary | Changes in levels of AMY-101 plasma level | On days 1, 2, 4, 7, 10, 14, 15, 21 |