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

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ClinicalTrials.gov Identifier: NCT05156671
Recruitment Status : Not yet recruiting
First Posted : December 14, 2021
Last Update Posted : March 16, 2022
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
COVID-19 Biological: Adrecizumab (HAM 8101) Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 218 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : March 2022
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : June 2023


Arm Intervention/treatment
Experimental: Adrecizumab (HAM 8101)
Adrecizumab (HAM 8101) on top of standard of care. Adrecizumab (HAM8101) is a humanized IgG1 monoclonal antibody (mAb). 4 mg/kg body weight Adrecizumab diluted in up to 100 mL saline as single dose infusion.
Biological: Adrecizumab (HAM 8101)
Drip infusion over 60 minutes.

Placebo Comparator: Placebo/ control substance (NaCl 0.9%)
100 mL saline as single dose infusion
Drug: Placebo
Drip infusion over 60 minutes
Other Name: Saline




Primary Outcome Measures :
  1. Time to clinical improvement [ Time Frame: 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 :
  1. Clinical status at day 28, as measured on the WHO 8-point ordinal scale [ Time Frame: 28 days ]
    Please see Outcome 1 for details on WHO 8-point ordinal scale

  2. Survival (time-to-event) until day 28 and end of follow-up (90 days) [ Time Frame: 90 days ]
  3. Rate of invasive mechanical ventilation until day 28 and day 90 [ Time Frame: 28 and 90 days ]
    defined as use of endotracheal or tracheostomy tube assisted ventilation

  4. Length of invasive mechanical ventilation until day 28 and day 90 [ Time Frame: 28 and 90 days ]
    defined as use of endotracheal or tracheostomy tube assisted ventilation

  5. Rate of ECMO therapy until day 28 and day 90 [ Time Frame: 28 and 90 days ]
  6. Length of ECMO therapy until day 28 and day 90 [ Time Frame: 28 and 90 days ]
  7. Length of stay at ICU after application of IMP up to a total of 90 days [ Time Frame: 90 days ]
  8. Length of hospital stay after application of IMP up to a total of 90 days [ Time Frame: 90 days ]
  9. All-cause rehospitalisation within 90 days [ Time Frame: 90 days ]
  10. Rate of renal replacement therapy until day 28 and day 90 [ Time Frame: 28 and 90 days ]
  11. Change in clinical status on the WHO 8-point ordinal scale for COVID-19 at days 7, 28, and 90 [ Time Frame: 7, 28 and 90 days ]
    Please see Outcome 1 for Details in WHO 8-point ordinal scale

  12. 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 ]
  13. Between-group difference in life quality as assessed by EQ-5D-5L at discharge, day 28, day 90 [ Time Frame: 28 and 90 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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]
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05156671


Contacts
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Contact: Mahir Karakas, MD, MBA +4915222817493 m.karakas@uke.de

Sponsors and Collaborators
Universitätsklinikum Hamburg-Eppendorf
Investigators
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Principal Investigator: Stefan Kluge, MD University Medical Center Hamburg-Eppendorf - Department of Intensive Care Medicine
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Responsible Party: Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier: NCT05156671    
Other Study ID Numbers: AGNES-19
First Posted: December 14, 2021    Key Record Dates
Last Update Posted: March 16, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Universitätsklinikum Hamburg-Eppendorf:
Vascular Integrity
Adrecizumab
Enibarcimab
acute lung injury
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases