COVID-19 MedDRA version: 23.0 Level: PT Classification code 10084268 Term: COVID-19 System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Adrecizumab
Product Code: HAM8101
Pharmaceutical Form: Solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous
Sponsors
University Medical Centre Hamburg-Eppendorf
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Hospitalization for moderate to severe COVID-19, defined as fulfilling at a minimum the following clinical status category on the WHO 8-point ordinal scale (corresponds to RKI score “severe” and “critical”): (i) “score 4” [oxygen via mask or nasal] • Bio-ADM =50 pg/mL or =30% increase until the end of the next day (with a minimum of 35 pg/mL at all) • DPP3 = 50 ng/mL • Age above 18 years at time of screening • Body weight below 150 kg at time of screening Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 109 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 109
Exclusion criteria
Exclusion criteria: • Life expectancy less than 3 months before COVID-19 at the discretion of the investigator • Invasive mechanical ventilation =72 hours at time-point of randomization • History of severe asthma, atopic allergy, severe immune or chronic inflammatory conditions (e.g. systemic lupus erythematosus) • Resuscitation > 45 minutes • Hypersensitivity to the active substance, to Adrecizumab or any of its excipients, or known serious hypersensitivity to other monoclonal antibodies • Currently receiving systemic chemotherapy and/or radiotherapy • Pre-existing severe chronic liver disease (i.e. Child-Pugh C) before COVID-19 hospitalization • Pre-existing dialysis therapy before COVID-19 hospitalization Note: RRT and/ or ECMO (initiated during COVID-19 hospitalization) are not an exclusion criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the AGNES-19 trial is to evaluate if improvement of vascular integrity with Adrecizumab on top of standard of care (SOC) is superior to placebo/ control substance (NaCl 0.9%) on top of SOC in reduction of the endpoint ”time to clinical improvement” until day 28 in patients with moderate to severe COVID-19. ;Secondary Objective: The secondary objectives of the AGNES-19 trial intend to evaluate the effect of Adrecizumab in com-parison to placebo, with respect to safety and tolerability of Adrecizumab on top of SOC in patients with moderate to severe COVID-19, clinical status at day 28, all-cause mortality, rate of new invasive mechanical ventilation, length of invasive mechanical ventilation, length of initial stay at ICU, rate of renal replacement therapy, change in SOFA score, clinical status according to ordinal WHO scale for COVID-19, and life quality as assessed by EQ5D.;Primary end point(s): Time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on the WHO 8-point ordinal scale or live discharge from the hospital, whichever came first. ;Timepoint(s) of evaluation of this end point: up to day 90 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy objectives are to compare the active treatment and placebo/ control sub-stance (NaCl 0.9%) groups with respect to: • Clinical status at day 28, as measured on the WHO 8-point ordinal scale • Survival (time-to-event) until day 28, and until end of follow-up (90 days) • Rate and length of invasive mechanical ventilation until day 28 and day 90, defined as use of endotracheal or tracheostomy tube assisted ventilation • Rate and length of ECMO therapy until day 28 and day 90 • Length of stay at ICU after application of IMP up to a total of 90 days • Length of hospital stay after application of IMP up to a total of 90 days • All-cause rehospitalisation within 90 days • Rate of renal replacement therapy until day 28 and day 90 • Change in clinical status on the WHO 8-point ordinal scale for COVID-19 at days 7, 28, 90 • Change in SOFA score sum (only during hospitalisation on ICU) within 24 hours of IMP administration (start of infusion), 48h, day 7 post-infusion • Between-group difference in life quality as assessed by EQ5D at discharge, day 28, day 90 Primary safety endpoint • Frequency and severity of SAEs/ AEs/SUSARs in both arms within 28 days • Mortality related to Adrecizumab • Interruption of infusion due to intolerability to Adrecizumab • New treatment-emergent adverse events (and changes in severity and frequency in these) related to Adrecizumab ;Timepoint(s) of evaluation of this end point: - day 28 and / or day 90 - days 7, 28, and 90 for change in clinical status on the WHO 8-point ordinal scale for COVID-19 - within 24 hours of IMP administration (start of infusion), 48h, day 7 post-infusion for change in SOFA score sum | — |
Countries
Germany
Contacts
Public ContactStefan Kluge
University Medical Centre Hamburg-Eppendorf
Outcome results
None listed