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

NCT05156671 | Terminated Phase 2 DMC

• 1 other identifier: AGNES-19
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 13

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.

Conditions

COVID-19

Keywords

Vascular Integrity; Adrecizumab; Enibarcimab; acute lung injury

Outcome Measures

Primary Outcomes (1)

• 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 -

  90 days

Secondary Outcomes (13)

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

  28 days

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

  90 days

• Rate of invasive mechanical ventilation until day 28 and day 90

  28 and 90 days

• Length of invasive mechanical ventilation until day 28 and day 90

  28 and 90 days

• Rate of ECMO therapy until day 28 and day 90

  28 and 90 days

Study Arms (2)

Adrecizumab (HAM 8101)

EXPERIMENTAL

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.

Biological: Adrecizumab (HAM 8101)

Placebo/ control substance (NaCl 0.9%)

PLACEBO COMPARATOR

100 mL saline as single dose infusion

Drug: Placebo

Interventions

Adrecizumab (HAM 8101) BIOLOGICAL

Drip infusion over 60 minutes.

Adrecizumab (HAM 8101)

Placebo DRUG

Drip infusion over 60 minutes

Also known as: Saline

Placebo/ control substance (NaCl 0.9%)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead

Study Sites (13)

Charité

Berlin, Germany

Location

Universitätsklinikum Essen

Essen, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany

Location

Universitätsmedizin Göttingen

Göttingen, Germany

Location

University Medical Center Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Medical School Hanover

Hanover, 30625, Germany

Location

Universitätsklinikum Mannheim

Mannheim, Germany

Location

Klinikum rechts der Isar TU München

München, Germany

Location

LMU München

München, Germany

Location

Universitätsklinikum Regensburg

Regensburg, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Germany

Location

Universitätsklinikum Ulm

Ulm, Germany

Location

MeSH Terms

Conditions

COVID-19; Acute Lung Injury

Interventions

enibarcimab; Sodium Chloride

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Lung Injury

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Stefan Kluge, MD

  University Medical Center Hamburg-Eppendorf - Department of Intensive Care Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2021
• First Posted: December 14, 2021
• Study Start: October 6, 2022
• Primary Completion: August 25, 2023
• Study Completion: November 15, 2023
• Last Updated: January 3, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (13)