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

• ClinicalTrials.gov Identifier: NCT04395456
• Recruitment Status: Unknown
• First Posted: May 20, 2020
• Last Update Posted: February 21, 2021
• Sponsor: Amyndas Pharmaceuticals S.A.
• Information provided by (Responsible Party): Amyndas Pharmaceuticals S.A.

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.

Condition or disease	Intervention/treatment	Phase
Acute Respiratory Distress Syndrome Due to SARS-CoV-2 Infection (Severe COVID19)	Drug: AMY-101; Other: WFI 5% glucose	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 144 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• 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)
• Estimated Study Start Date: September 2021
• Estimated Primary Completion Date: September 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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 ]
2. 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.

Secondary Outcome Measures :

1. 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.
2. Proportion of patients surviving [ Time Frame: Through to day 44 ]
3. 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.
4. Cumulative incidence of resolution of ARDS (defined as PaO2/FiO2 ≥200 in room air) [ Time Frame: Through day 44 ]
5. Cumulative incidence of freedom from oxygen requirement [ Time Frame: Through day 44 ]
6. Proportion of patients requiring invasive mechanical ventilation due to worsening of ARDS [ Time Frame: Within 14 days after inclusion in the study ]
7. Proportion of patients requiring non-invasive mechanical ventilation (NIV) due to worsening of ARDS [ Time Frame: Within 14 days after inclusion in the study ]
8. Proportion of patients developing thrombotic microangiopathies [ Time Frame: Through day 44 ]
9. Changes in PaO2 and PaO2/FIO2 [ Time Frame: Through day 44 ]
10. Changes in quick Sequential Organ Failure Assessment Score (qSOFA: respiratory rate, systolic blood pressure, Glasgow Coma Scale (GCS) [ Time Frame: Through day 44 ]
11. Changes in maximal and minimal cardiovascular parameters: Respiratory rate [ Time Frame: Through day 44 ]
12. Changes in maximal and minimal cardiovascular parameters: Heart Rate [ Time Frame: Through day 44 ]
13. 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 ]
14. Length of stay in ICU [ Time Frame: Through day 44 ]
15. Cumulative incidence of discharge from hospital [ Time Frame: Through day 44 ]
16. Number of adverse events [ Time Frame: Through day 44 ]
17. Changes in levels of anti-drug antibodies [ Time Frame: On day 0 , 14 and 44 ]
18. 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 ]
19. 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 ]
20. 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 ]
21. Changes in levels of AMY-101 plasma level [ Time Frame: On days 1, 2, 4, 7, 10, 14, 15, 21 ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

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.

• Responsible Party: Amyndas Pharmaceuticals S.A.
• ClinicalTrials.gov Identifier: NCT04395456
• Other Study ID Numbers: AMY-101_SAVE
• First Posted: May 20, 2020
• Last Update Posted: February 21, 2021
• Last Verified: February 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Syndrome; Disease; Pathologic Processes; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury