COVID-19Phase 2AGNES-19NCT05156671
Adrecizumab (HAM8101) to Improve Prognosis and Outcomes in COVID-19 Trial
A Phase 2 study testing Adrecizumab (HAM 8101) in people with COVID-19, run by Universitätsklinikum Hamburg-Eppendorf at 13 sites in Germany.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Adrecizumab (HAM 8101)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 13 sitesGermany
- Study dates
- 6 Oct 2022to 15 Nov 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Germany13 sites
Charité
Berlin
Universitätsklinikum Essen
Essen
Universitätsklinikum Frankfurt
Frankfurt
Universitätsklinikum Freiburg
Freiburg im Breisgau
Universitätsmedizin Göttingen
Göttingen
University Medical Center Hamburg Eppendorf
Hamburg, 20246
Medical School Hanover
Hanover, 30625
Universitätsklinikum Mannheim
Mannheim
Klinikum rechts der Isar TU München
München
LMU München
München
Universitätsklinikum Regensburg
Regensburg
Universitätsklinikum Tübingen
Tübingen
Universitätsklinikum Ulm
Ulm
About this study
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
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
- Being tested
- Adrecizumab (HAM 8101), Placebo
- Keywords
- Vascular Integrity, Adrecizumab, Enibarcimab, acute lung injury
- Medical subject headings
- COVID-19, Acute Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adrecizumab (HAM 8101)Biological
Drip infusion over 60 minutes.
PlaceboDrug
Also called Saline
Drip infusion over 60 minutes
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Adrecizumab (HAM 8101) |
| Placebo/ control substance (NaCl 0.9%) | Placebo comparator | 100 mL saline as single dose infusion Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 -
Measured: 90 days
Secondary outcomes (13)
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
Measured: 28 days
Survival (time-to-event) until day 28 and end of follow-up (90 days)
Measured: 90 days
Rate of invasive mechanical ventilation until day 28 and day 90
defined as use of endotracheal or tracheostomy tube assisted ventilation
Measured: 28 and 90 days
Length of invasive mechanical ventilation until day 28 and day 90
defined as use of endotracheal or tracheostomy tube assisted ventilation
Measured: 28 and 90 days
Rate of ECMO therapy until day 28 and day 90
Measured: 28 and 90 days
Length of ECMO therapy until day 28 and day 90
Measured: 28 and 90 days
Length of stay at ICU after application of IMP up to a total of 90 days
Measured: 90 days
Length of hospital stay after application of IMP up to a total of 90 days
Measured: 90 days
All-cause rehospitalisation within 90 days
Measured: 90 days
Rate of renal replacement therapy until day 28 and day 90
Measured: 28 and 90 days
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
Measured: 7, 28 and 90 days
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
Measured: 24 hours, 48 hours and 7 days post-infusion
Between-group difference in life quality as assessed by EQ-5D-5L at discharge, day 28, day 90
Measured: 28 and 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2021
- Study start6 Oct 2022
- Primary completion25 Aug 2023
- Study completion15 Nov 2023
Why it stopped: Due to poor recruitment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Universitätsklinikum Hamburg-EppendorfThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitätsklinikum Hamburg-Eppendorf
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stefan Kluge, MD, Principal investigator, University Medical Center Hamburg-Eppendorf - Department of Intensive Care Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05156671
- Sponsor's protocol ID
- AGNES-19
- Acronym
- AGNES-19
- Status last verified
- Dec 2023
- First submitted
- 2 Dec 2021
- Last updated
- 3 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05156671
- Acronym / sponsor ID
- AGNES-19 / AGNES-19
- Conditions
- COVID-19
- Keywords
- Vascular Integrity, Adrecizumab, Enibarcimab, acute lung injury
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to poor recruitment.
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Universitätsklinikum Hamburg-EppendorfUniversity, hospital or other
- Study start
- 6 Oct 2022 (actual)
- Primary completion
- 25 Aug 2023 (actual)
- Study completion
- 15 Nov 2023 (actual)
- First posted
- 14 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adrecizumab (HAM 8101) | Experimental | Biological: Adrecizumab (HAM 8101)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. |
| Placebo/ control substance (NaCl 0.9%) | Placebo comparator | Drug: Placebo100 mL saline as single dose infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adrecizumab (HAM 8101)Drip infusion over 60 minutes. | Biological | Adrecizumab (HAM 8101) |
| PlaceboAlso: SalineDrip infusion over 60 minutes | Drug | Placebo/ control substance (NaCl 0.9%) |
Primary outcome
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 -
13 secondary outcomes
Clinical status at day 28, as measured on the WHO 8-point ordinal scale
Time frame: 28 days
Survival (time-to-event) until day 28 and end of follow-up (90 days)
Time frame: 90 days
Rate of invasive mechanical ventilation until day 28 and day 90
Time frame: 28 and 90 days
Length of invasive mechanical ventilation until day 28 and day 90
Time frame: 28 and 90 days
Rate of ECMO therapy until day 28 and day 90
Time frame: 28 and 90 days
Length of ECMO therapy until day 28 and day 90
Time frame: 28 and 90 days
Length of stay at ICU after application of IMP up to a total of 90 days
Time frame: 90 days
Length of hospital stay after application of IMP up to a total of 90 days
Time frame: 90 days
All-cause rehospitalisation within 90 days
Time frame: 90 days
Rate of renal replacement therapy until day 28 and day 90
Time frame: 28 and 90 days
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
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
Between-group difference in life quality as assessed by EQ-5D-5L at discharge, day 28, day 90
Time frame: 28 and 90 days
Results and safety
The study was stopped early (reason given: Due to poor recruitment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefan Kluge, MD principal investigator
University Medical Center Hamburg-Eppendorf - Department of Intensive Care Medicine
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Adrecizumab (HAM 8101) in people with COVID-19, run by Universitätsklinikum Hamburg-Eppendorf at 13 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Due to poor recruitment.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to clinical improvement (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2024.