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

Primary Purpose

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

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
AMY-101
WFI 5% glucose
Sponsored by
Amyndas Pharmaceuticals S.A.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Respiratory Distress Syndrome Due to SARS-CoV-2 Infection (Severe COVID19)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    AMY-101

    Placebo

    Arm Description

    Outcomes

    Primary Outcome Measures

    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).
    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.

    Secondary Outcome Measures

    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.
    Proportion of patients surviving
    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.
    Cumulative incidence of resolution of ARDS (defined as PaO2/FiO2 ≥200 in room air)
    Cumulative incidence of freedom from oxygen requirement
    Proportion of patients requiring invasive mechanical ventilation due to worsening of ARDS
    Proportion of patients requiring non-invasive mechanical ventilation (NIV) due to worsening of ARDS
    Proportion of patients developing thrombotic microangiopathies
    Changes in PaO2 and PaO2/FIO2
    Changes in quick Sequential Organ Failure Assessment Score (qSOFA: respiratory rate, systolic blood pressure, Glasgow Coma Scale (GCS)
    Changes in maximal and minimal cardiovascular parameters: Respiratory rate
    Changes in maximal and minimal cardiovascular parameters: Heart Rate
    Changes in levels of biomarkers of inflammation (CBC, CRP, Ferritin, Procalcitonin, D-dimers, LDH)
    Length of stay in ICU
    Cumulative incidence of discharge from hospital
    Number of adverse events
    Changes in levels of anti-drug antibodies
    Changes in levels of biomarkers of complement activity: C3, C3a, C5a, sC5b-9
    Changes in levels of biomarkers of cytokine release syndrome: IL-1, IL-6, IL-12
    Changes in levels of Club Cell protein CC16 (biomarker of lung damage )
    Changes in levels of AMY-101 plasma level

    Full Information

    First Posted
    May 19, 2020
    Last Updated
    February 19, 2021
    Sponsor
    Amyndas Pharmaceuticals S.A.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04395456
    Brief Title
    A Study of the C3 Inhibitor AMY-101 in Patients With ARDS Due to COVID-19 (SAVE)
    Acronym
    SAVE
    Official 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)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2021
    Overall Recruitment Status
    Unknown status
    Study Start Date
    September 2021 (Anticipated)
    Primary Completion Date
    September 2022 (Anticipated)
    Study Completion Date
    December 2022 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Amyndas Pharmaceuticals S.A.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Acute Respiratory Distress Syndrome Due to SARS-CoV-2 Infection (Severe COVID19)

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    Participant
    Allocation
    Randomized
    Enrollment
    144 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    AMY-101
    Arm Type
    Experimental
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Intervention Type
    Drug
    Intervention Name(s)
    AMY-101
    Intervention Description
    C3 complement inhibitor
    Intervention Type
    Other
    Intervention Name(s)
    WFI 5% glucose
    Intervention Description
    Placebo
    Primary Outcome Measure Information:
    Title
    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
    Title
    The proportion of patients assigned to each category, of a six-category ordinal scale.
    Description
    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 Outcome Measure Information:
    Title
    The proportion of patients assigned to each category, of a six-category ordinal scale.
    Description
    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
    On days 7, 14, and 44
    Title
    Proportion of patients surviving
    Time Frame
    Through to day 44
    Title
    Proportion of respiratory failure-free survival
    Description
    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.
    Time Frame
    Day 44
    Title
    Cumulative incidence of resolution of ARDS (defined as PaO2/FiO2 ≥200 in room air)
    Time Frame
    Through day 44
    Title
    Cumulative incidence of freedom from oxygen requirement
    Time Frame
    Through day 44
    Title
    Proportion of patients requiring invasive mechanical ventilation due to worsening of ARDS
    Time Frame
    Within 14 days after inclusion in the study
    Title
    Proportion of patients requiring non-invasive mechanical ventilation (NIV) due to worsening of ARDS
    Time Frame
    Within 14 days after inclusion in the study
    Title
    Proportion of patients developing thrombotic microangiopathies
    Time Frame
    Through day 44
    Title
    Changes in PaO2 and PaO2/FIO2
    Time Frame
    Through day 44
    Title
    Changes in quick Sequential Organ Failure Assessment Score (qSOFA: respiratory rate, systolic blood pressure, Glasgow Coma Scale (GCS)
    Time Frame
    Through day 44
    Title
    Changes in maximal and minimal cardiovascular parameters: Respiratory rate
    Time Frame
    Through day 44
    Title
    Changes in maximal and minimal cardiovascular parameters: Heart Rate
    Time Frame
    Through day 44
    Title
    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
    Title
    Length of stay in ICU
    Time Frame
    Through day 44
    Title
    Cumulative incidence of discharge from hospital
    Time Frame
    Through day 44
    Title
    Number of adverse events
    Time Frame
    Through day 44
    Title
    Changes in levels of anti-drug antibodies
    Time Frame
    On day 0 , 14 and 44
    Title
    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
    Title
    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
    Title
    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
    Title
    Changes in levels of AMY-101 plasma level
    Time Frame
    On days 1, 2, 4, 7, 10, 14, 15, 21

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    32327719
    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.
    Results Reference
    background
    PubMed Identifier
    32360516
    Citation
    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.
    Results Reference
    background

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

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