Clinical trial NCT05156671: Adrecizumab (HAM8101) to Improve Prognosis and Outcomes in COVID-19 Trial
Official title: Multicenter, Randomized, Double-blind, Biomarker-guided, Phase II Trial With Adrecizumab (HAM 8101) to Improve proGNosis and outcomES in Patients With Moderate to Severe COVID-19
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Keywords: Vascular Integrity
Adrecizumab
Enibarcimab
acute lung injury
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
First posted: 2021-12-14
Enrollment: 16
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 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.


Eligibility criteria: 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

Primary outcomes:
measure: Time to clinical improvement
timeFrame: 90 days
Secondary outcomes:
measure: Clinical status at day 28, as measured on the WHO 8-point ordinal scale
timeFrame: 28 days
measure: Survival (time-to-event) until day 28 and end of follow-up (90 days)
timeFrame: 90 days
measure: Rate of invasive mechanical ventilation until day 28 and day 90
timeFrame: 28 and 90 days
measure: Length of invasive mechanical ventilation until day 28 and day 90
timeFrame: 28 and 90 days
measure: Rate of ECMO therapy until day 28 and day 90
timeFrame: 28 and 90 days
measure: Length of ECMO therapy until day 28 and day 90
timeFrame: 28 and 90 days
measure: Length of stay at ICU after application of IMP up to a total of 90 days
timeFrame: 90 days
measure: Length of hospital stay after application of IMP up to a total of 90 days
timeFrame: 90 days
measure: All-cause rehospitalisation within 90 days
timeFrame: 90 days
measure: Rate of renal replacement therapy until day 28 and day 90
timeFrame: 28 and 90 days
measure: Change in clinical status on the WHO 8-point ordinal scale for COVID-19 at days 7, 28, and 90
timeFrame: 7, 28 and 90 days
measure: 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
timeFrame: 24 hours, 48 hours and 7 days post-infusion
measure: Between-group difference in life quality as assessed by EQ-5D-5L at discharge, day 28, day 90
timeFrame: 28 and 90 days
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
city: Hamburg
country: Germany
facility: University Medical Center Hamburg Eppendorf
city: Hanover
country: Germany
facility: Medical School Hanover
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim
city: München
country: Germany
facility: Klinikum rechts der Isar TU München
city: München
country: Germany
facility: LMU München
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
Study officials:
affiliation: University Medical Center Hamburg-Eppendorf - Department of Intensive Care Medicine
name: Stefan Kluge, MD
role: PRINCIPAL_INVESTIGATOR
References: