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

Primary Purpose

COVID-19

Status
Recruiting
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Adrecizumab (HAM 8101)
Placebo
Sponsored by
Universitätsklinikum Hamburg-Eppendorf
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring Vascular Integrity, Adrecizumab, Enibarcimab, acute lung injury

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Hospitalization for moderate to severe COVID-19, defined as ful-filling 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 ≤50 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
  • 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

Sites / Locations

  • Charité
  • Universitätsklinikum EssenRecruiting
  • Universitätsklinikum FrankfurtRecruiting
  • Universitätsklinikum Freiburg
  • Universitätsmedizin GöttingenRecruiting
  • University Medical Center Hamburg EppendorfRecruiting
  • Medical School HanoverRecruiting
  • Universitätsklinikum Mannheim
  • Klinikum rechts der Isar TU München
  • LMU MünchenRecruiting
  • Universitätsklinikum Regensburg
  • Universitätsklinikum Tübingen
  • Universitätsklinikum Ulm

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Adrecizumab (HAM 8101)

Placebo/ control substance (NaCl 0.9%)

Arm Description

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.

100 mL saline as single dose infusion

Outcomes

Primary Outcome Measures

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 -

Secondary Outcome Measures

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
Survival (time-to-event) until day 28 and end of follow-up (90 days)
Rate of invasive mechanical ventilation until day 28 and day 90
defined as use of endotracheal or tracheostomy tube assisted ventilation
Length of invasive mechanical ventilation until day 28 and day 90
defined as use of endotracheal or tracheostomy tube assisted ventilation
Rate of ECMO therapy until day 28 and day 90
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, and 90
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
Between-group difference in life quality as assessed by EQ-5D-5L at discharge, day 28, day 90

Full Information

First Posted
December 2, 2021
Last Updated
July 17, 2023
Sponsor
Universitätsklinikum Hamburg-Eppendorf
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1. Study Identification

Unique Protocol Identification Number
NCT05156671
Brief Title
Adrecizumab (HAM8101) to Improve Prognosis and Outcomes in COVID-19 Trial
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 6, 2022 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitätsklinikum Hamburg-Eppendorf

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
Vascular Integrity, Adrecizumab, Enibarcimab, acute lung injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Adrecizumab (HAM 8101)
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo/ control substance (NaCl 0.9%)
Arm Type
Placebo Comparator
Arm Description
100 mL saline as single dose infusion
Intervention Type
Biological
Intervention Name(s)
Adrecizumab (HAM 8101)
Intervention Description
Drip infusion over 60 minutes.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Saline
Intervention Description
Drip infusion over 60 minutes
Primary Outcome Measure Information:
Title
Time to clinical improvement
Description
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 -
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Clinical status at day 28, as measured on the WHO 8-point ordinal scale
Description
Please see Outcome 1 for details on WHO 8-point ordinal scale
Time Frame
28 days
Title
Survival (time-to-event) until day 28 and end of follow-up (90 days)
Time Frame
90 days
Title
Rate of invasive mechanical ventilation until day 28 and day 90
Description
defined as use of endotracheal or tracheostomy tube assisted ventilation
Time Frame
28 and 90 days
Title
Length of invasive mechanical ventilation until day 28 and day 90
Description
defined as use of endotracheal or tracheostomy tube assisted ventilation
Time Frame
28 and 90 days
Title
Rate of ECMO therapy until day 28 and day 90
Time Frame
28 and 90 days
Title
Length of ECMO therapy until day 28 and day 90
Time Frame
28 and 90 days
Title
Length of stay at ICU after application of IMP up to a total of 90 days
Time Frame
90 days
Title
Length of hospital stay after application of IMP up to a total of 90 days
Time Frame
90 days
Title
All-cause rehospitalisation within 90 days
Time Frame
90 days
Title
Rate of renal replacement therapy until day 28 and day 90
Time Frame
28 and 90 days
Title
Change in clinical status on the WHO 8-point ordinal scale for COVID-19 at days 7, 28, and 90
Description
Please see Outcome 1 for Details in WHO 8-point ordinal scale
Time Frame
7, 28 and 90 days
Title
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
Title
Between-group difference in life quality as assessed by EQ-5D-5L at discharge, day 28, day 90
Time Frame
28 and 90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mahir Karakas, MD, MBA
Phone
+4915222817493
Email
m.karakas@uke.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stefan Kluge, MD
Organizational Affiliation
University Medical Center Hamburg-Eppendorf - Department of Intensive Care Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charité
City
Berlin
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Universitätsklinikum Essen
City
Essen
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marc Moritz Berger, Prof.
Facility Name
Universitätsklinikum Frankfurt
City
Frankfurt
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kai Zacharowski, Prof. Dr. Dr.
Facility Name
Universitätsklinikum Freiburg
City
Freiburg
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Universitätsmedizin Göttingen
City
Göttingen
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Onnen Mörer, Prof. Dr. med.
Facility Name
University Medical Center Hamburg Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mahir Karakas
Phone
+4915222817493
Email
m.karakas@uke.de
Facility Name
Medical School Hanover
City
Hanover
ZIP/Postal Code
30625
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tobias Welte, Prof.
Email
Welte.Tobias@mh-hannover.de
Facility Name
Universitätsklinikum Mannheim
City
Mannheim
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Klinikum rechts der Isar TU München
City
München
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
LMU München
City
München
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandra Frank, PD Dr. med.
Facility Name
Universitätsklinikum Regensburg
City
Regensburg
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Universitätsklinikum Tübingen
City
Tübingen
Country
Germany
Individual Site Status
Active, not recruiting
Facility Name
Universitätsklinikum Ulm
City
Ulm
Country
Germany
Individual Site Status
Active, not recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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

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