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

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ClinicalTrials.gov Identifier: NCT04395456
Recruitment Status : Not yet recruiting
First Posted : May 20, 2020
Last Update Posted : February 21, 2021
Sponsor:
Information provided by (Responsible Party):
Amyndas Pharmaceuticals S.A.

Tracking Information
First Submitted Date  ICMJE May 19, 2020
First Posted Date  ICMJE May 20, 2020
Last Update Posted Date February 21, 2021
Estimated Study Start Date  ICMJE September 2021
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 19, 2020)
  • 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. [ Time Frame: 21 days ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2020)
  • The proportion of patients assigned to each category, of a six-category ordinal scale. [ Time Frame: On days 7, 14, and 44 ]
    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 [ Time Frame: Through to day 44 ]
  • Proportion of respiratory failure-free survival [ Time Frame: Day 44 ]
    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.
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the C3 Inhibitor AMY-101 in Patients With ARDS Due to COVID-19 (SAVE)
Official Title  ICMJE 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)
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Acute Respiratory Distress Syndrome Due to SARS-CoV-2 Infection (Severe COVID19)
Intervention  ICMJE
  • Drug: AMY-101
    C3 complement inhibitor
  • Other: WFI 5% glucose
    Placebo
Study Arms  ICMJE
  • Experimental: AMY-101
    Intervention: Drug: AMY-101
  • Placebo Comparator: Placebo
    Intervention: Other: WFI 5% glucose
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 19, 2020)
144
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04395456
Other Study ID Numbers  ICMJE AMY-101_SAVE
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Amyndas Pharmaceuticals S.A.
Study Sponsor  ICMJE Amyndas Pharmaceuticals S.A.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Amyndas Pharmaceuticals S.A.
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP