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

COVID-19 Clinical Trial

— AGNES-19  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05156671
• Other study ID #: AGNES-19
• Status: Terminated
• Phase: Phase 2
• Start date: October 6, 2022
• Est. completion date: November 15, 2023

Study information

• Verified date: December 2023
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: November 15, 2023
• Est. primary completion date: August 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

Biological:
• Adrecizumab (HAM 8101)
Drip infusion over 60 minutes.

Drug:
• Placebo
Drip infusion over 60 minutes

Locations

Country	Name	City	State
Germany	Charité	Berlin
Germany	Universitätsklinikum Essen	Essen
Germany	Universitätsklinikum Frankfurt	Frankfurt
Germany	Universitätsklinikum Freiburg	Freiburg
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	Universitätsklinikum Regensburg	Regensburg
Germany	Universitätsklinikum Tübingen	Tübingen
Germany	Universitätsklinikum Ulm	Ulm

Sponsors (1)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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; Ambulatory No limitation of activities; Ambulatory Limitation of activities; Hospitalized, mild disease No oxygen therapy; Hospitalized, mild disease Oxygen by mask or nasal cannulae; Hospitalized, severe disease Non-invasive ventilation on high-flow oxygen; Hospitalized, severe disease Intubation and invasive mechanical ventilation; Hospitalized, severe disease Invasive mechanical ventilation and additional organ support; Death -	90 days
Secondary	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	28 days
Secondary	Survival (time-to-event) until day 28 and end of follow-up (90 days)		90 days
Secondary	Rate of invasive mechanical ventilation until day 28 and day 90	defined as use of endotracheal or tracheostomy tube assisted ventilation	28 and 90 days
Secondary	Length of invasive mechanical ventilation until day 28 and day 90	defined as use of endotracheal or tracheostomy tube assisted ventilation	28 and 90 days
Secondary	Rate of ECMO therapy until day 28 and day 90		28 and 90 days
Secondary	Length of ECMO therapy until day 28 and day 90		28 and 90 days
Secondary	Length of stay at ICU after application of IMP up to a total of 90 days		90 days
Secondary	Length of hospital stay after application of IMP up to a total of 90 days		90 days
Secondary	All-cause rehospitalisation within 90 days		90 days
Secondary	Rate of renal replacement therapy until day 28 and day 90		28 and 90 days
Secondary	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	7, 28 and 90 days
Secondary	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
Secondary	Between-group difference in life quality as assessed by EQ-5D-5L at discharge, day 28, day 90		28 and 90 days