Adrecizumab (HAM8101) to Improve Prognosis and Outcomes in COVID-19 Trial
- Conditions
- COVID-19
- Interventions
- Biological: Adrecizumab (HAM 8101)Drug: Placebo
- Registration Number
- NCT05156671
- Lead Sponsor
- Universitätsklinikum Hamburg-Eppendorf
- Brief Summary
The clinical trial is designed as a prospective, multi-center, double-blind, randomised, placebo-controlled, interventional trial to assess safety, tolerability and efficacy of Adrecizumab (on top of SOC) in patients with COVID-19, and to evaluate if improvement of vascular integrity with Adrecizumab on top of SOC is superior to placebo/ control substance (NaCl 0.9%) on top of SOC in reduction of morbidity and mortality endpoints in patients with COVID-19.
The main reason for admission to ICU and need for mechanical ventilation of these patients is acute lung injury within a broad pneumonic spectrum, increased ventricular filling pressures and resulting congestion. It is hypothesized, that Adrenomedullin (ADM) is a key player in the (dys)-regulation of vascular integrity (Figure 2). Adrecizumab is the first-in-class humanized monoclonal anti-Adrenomedullin antibody, and acts as a long-lasting plasma Adrenomedullin enhancer stabilizing barrier function at a reasonable safety profile. The mode of action for the anti-Adrenomedullin antibody Adrecizumab has been developed on the basis of published data, own experimental data and theoretical considerations.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 16
- Hospitalization with moderate to severe COVID-19, defined as fulfilling at a minimum the following clinical status category on the WHO 8-point ordinal scale: (i) "score 4" [oxygen via mask or nasal]
- Laboratory-confirmed SARS-CoV-2 infection at index hospitalisation as determined by PCR or other validated commercial or public health assay
- 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 ≤30 ng/mL
- Age ≥18 years at time of screening
- Body weight ≤ 150 kg at time of screening
- 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
- Resuscitation > 45 minutes
- Hypersensitivity to the active substance, to Adrecizumab or any of its excipients, or known serious hypersensitivity to other monoclonal antibodies
- Uncontrolled haematological/ oncological malignancies
- Pre-existing severe chronic liver disease (i.e. Child-Pugh C) before COVID-19 hospitalization
- Absolute neutropenia <500 per μL
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Adrecizumab (HAM 8101) Adrecizumab (HAM 8101) Adrecizumab (HAM 8101) on top of standard of care. Adrecizumab (HAM8101) is a humanized IgG1 monoclonal antibody (mAb). 2 mg/kg body weight Adrecizumab diluted in up to 100 mL saline as single dose infusion. Placebo/ control substance (NaCl 0.9%) Placebo 100 mL saline as single dose infusion
- Primary Outcome Measures
Name Time Method Time to clinical improvement 90 days Time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on the World Health Organisation 8-point ordinal scale or live discharge from the hospital, whichever came first.
WHO 8-point ordinal scale
1. Ambulatory No limitation of activities
2. Ambulatory Limitation of activities
3. Hospitalized, mild disease No oxygen therapy
4. Hospitalized, mild disease Oxygen by mask or nasal cannulae
5. Hospitalized, severe disease Non-invasive ventilation on high-flow oxygen
6. Hospitalized, severe disease Intubation and invasive mechanical ventilation
7. Hospitalized, severe disease Invasive mechanical ventilation and additional organ support
8. Death -
- Secondary Outcome Measures
Name Time Method Clinical status at day 28, as measured on the WHO 8-point ordinal scale 28 days Please see Outcome 1 for details on WHO 8-point ordinal scale
Rate of invasive mechanical ventilation until day 28 and day 90 28 and 90 days defined as use of endotracheal or tracheostomy tube assisted ventilation
Survival (time-to-event) until day 28 and end of follow-up (90 days) 90 days Length of invasive mechanical ventilation until day 28 and day 90 28 and 90 days defined as use of endotracheal or tracheostomy tube assisted ventilation
Rate of ECMO therapy until day 28 and day 90 28 and 90 days Length of ECMO therapy until day 28 and day 90 28 and 90 days Length of stay at ICU after application of IMP up to a total of 90 days 90 days Length of hospital stay after application of IMP up to a total of 90 days 90 days All-cause rehospitalisation within 90 days 90 days Rate of renal replacement therapy until day 28 and day 90 28 and 90 days Change in clinical status on the WHO 8-point ordinal scale for COVID-19 at days 7, 28, and 90 7, 28 and 90 days Please see Outcome 1 for Details in WHO 8-point ordinal scale
Change in SOFA score sum (only during hospitalization on ICU) with-in 24 hours of IMP administration (start of infusion), 48 hours, day 7 post-infusion 24 hours, 48 hours and 7 days post-infusion Between-group difference in life quality as assessed by EQ-5D-5L at discharge, day 28, day 90 28 and 90 days
Trial Locations
- Locations (13)
Universitätsklinikum Essen
🇩🇪Essen, Germany
Universitätsklinikum Frankfurt
🇩🇪Frankfurt, Germany
Charité
🇩🇪Berlin, Germany
University Medical Center Hamburg Eppendorf
🇩🇪Hamburg, Germany
Universitätsklinikum Freiburg
🇩🇪Freiburg, Germany
Universitätsmedizin Göttingen
🇩🇪Göttingen, Germany
Klinikum rechts der Isar TU München
🇩🇪München, Germany
Medical School Hanover
🇩🇪Hanover, Germany
Universitätsklinikum Mannheim
🇩🇪Mannheim, Germany
LMU München
🇩🇪München, Germany
Universitätsklinikum Regensburg
🇩🇪Regensburg, Germany
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany