Adrecizumab (HAM8101) to Improve Prognosis and Outcomes in COVID-19 Trial

Phase 2TerminatedNCT05156671

Universitätsklinikum Hamburg-Eppendorf16 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

COVID-19

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 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 * 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

Locations (13)

Charité

Berlin, Germany

Universitätsklinikum Essen

Essen, Germany

Universitätsklinikum Frankfurt

Frankfurt, Germany

Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany

Universitätsmedizin Göttingen

Göttingen, Germany

University Medical Center Hamburg Eppendorf

Hamburg, Germany

Medical School Hanover

Hanover, Germany

Universitätsklinikum Mannheim

Mannheim, Germany

Klinikum rechts der Isar TU München

München, Germany

LMU München

München, Germany

...and 3 more locations

Outcomes

Primary Outcomes

Time to clinical improvement

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 -

Time frame: 90 days

Secondary Outcomes

Clinical status at day 28, as measured on the WHO 8-point ordinal scale

Please see Outcome 1 for details on WHO 8-point ordinal scale

Time frame: 28 days

Survival (time-to-event) until day 28 and end of follow-up (90 days)

Time frame: 90 days

Rate of invasive mechanical ventilation until day 28 and day 90

defined as use of endotracheal or tracheostomy tube assisted ventilation

Time frame: 28 and 90 days

Length of invasive mechanical ventilation until day 28 and day 90

defined as use of endotracheal or tracheostomy tube assisted ventilation

Time frame: 28 and 90 days

Rate of ECMO therapy until day 28 and day 90

Time frame: 28 and 90 days

Length of ECMO therapy until day 28 and day 90

Time frame: 28 and 90 days

Length of stay at ICU after application of IMP up to a total of 90 days

Time frame: 90 days

Length of hospital stay after application of IMP up to a total of 90 days

Time frame: 90 days

All-cause rehospitalisation within 90 days

Time frame: 90 days

Rate of renal replacement therapy until day 28 and day 90

Time frame: 28 and 90 days

Change in clinical status on the WHO 8-point ordinal scale for COVID-19 at days 7, 28, and 90

Please see Outcome 1 for Details in WHO 8-point ordinal scale

Time frame: 7, 28 and 90 days

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

Time frame: 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

Time frame: 28 and 90 days