Clinical trial NCT04395456: A Study of the C3 Inhibitor AMY-101 in Patients With ARDS Due to COVID-19 (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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Respiratory Distress Syndrome Due to SARS-CoV-2 Infection (Severe COVID19)
Lead sponsor: Amyndas Pharmaceuticals S.A.
Sponsor class: INDUSTRY
First posted: 2020-05-20
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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).
timeFrame: 21 days
measure: The proportion of patients assigned to each category, of a six-category ordinal scale.
timeFrame: 21 days
Secondary outcomes:
measure: The proportion of patients assigned to each category, of a six-category ordinal scale.
timeFrame: On days 7, 14, and 44
measure: Proportion of patients surviving
timeFrame: Through to day 44
measure: Proportion of respiratory failure-free survival
timeFrame: Day 44
measure: Cumulative incidence of resolution of ARDS (defined as PaO2/FiO2 ≥200 in room air)
timeFrame: Through day 44
measure: Cumulative incidence of freedom from oxygen requirement
timeFrame: Through day 44
measure: Proportion of patients requiring invasive mechanical ventilation due to worsening of ARDS
timeFrame: Within 14 days after inclusion in the study
measure: Proportion of patients requiring non-invasive mechanical ventilation (NIV) due to worsening of ARDS
timeFrame: Within 14 days after inclusion in the study
measure: Proportion of patients developing thrombotic microangiopathies
timeFrame: Through day 44
measure: Changes in PaO2 and PaO2/FIO2
timeFrame: Through day 44
measure: Changes in quick Sequential Organ Failure Assessment Score (qSOFA: respiratory rate, systolic blood pressure, Glasgow Coma Scale (GCS)
timeFrame: Through day 44
measure: Changes in maximal and minimal cardiovascular parameters: Respiratory rate
timeFrame: Through day 44
measure: Changes in maximal and minimal cardiovascular parameters: Heart Rate
timeFrame: Through day 44
measure: Changes in levels of biomarkers of inflammation (CBC, CRP, Ferritin, Procalcitonin, D-dimers, LDH)
timeFrame: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44
measure: Length of stay in ICU
timeFrame: Through day 44
measure: Cumulative incidence of discharge from hospital
timeFrame: Through day 44
measure: Number of adverse events
timeFrame: Through day 44
measure: Changes in levels of anti-drug antibodies
timeFrame: On day 0 , 14 and 44
measure: Changes in levels of biomarkers of complement activity: C3, C3a, C5a, sC5b-9
timeFrame: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44
measure: Changes in levels of biomarkers of cytokine release syndrome: IL-1, IL-6, IL-12
timeFrame: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44
measure: Changes in levels of Club Cell protein CC16 (biomarker of lung damage )
timeFrame: On days 0, 1, 2, 4, 7, 10, 14, 21 and 44
measure: Changes in levels of AMY-101 plasma level
timeFrame: On days 1, 2, 4, 7, 10, 14, 15, 21
Other outcomes:
Locations:
Study officials:
References:
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.
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.