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

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)

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 Overview

• Status: Unknown
• Conditions: Acute Respiratory Distress Syndrome Due to SARS-CoV-2 Infection (Severe COVID19)
• Intervention / Treatment: Drug: AMY-101; Other: WFI 5% glucose

• Study Type: Interventional
• Enrollment (Anticipated): 144
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: WFI 5% glucose; Placebo
Experimental: AMY-101	Drug: AMY-101; C3 complement inhibitor

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Amyndas Pharmaceuticals S.A.

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2021
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: May 19, 2020
• First Submitted That Met QC Criteria: May 19, 2020
• First Posted (Actual): May 20, 2020

Study Record Updates

• Last Update Posted (Actual): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 19, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: AMY-101_SAVE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No