Acute Heart FailurePhase 2ADESTENCT04252937
Adrecizumab Dose Escalation Safety and Tolerability Evaluation (ADESTE)
A Phase 2 study testing Adrecizumab in people with Acute Heart Failure, run by GREAT Network Italy at 2 sites in Indonesia.
Trial summary
This is an open, standard therapy controlled clinical trial using a single intravenous infusion of HAM8101 (Adrecizumab) in patients hospitalized for AHF. This study will serve as a safety trial for HAM8101 (Adrecizumab) in AHF, using a dose escalating design. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Heart Failure
- What is being tested?
- Adrecizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesIndonesia
- Study dates
- 15 Dec 2019to 31 Mar 2022
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years;
- Hospitalization due to the primary diagnosis of AHF, based on ESC 2016 Guidelines;
- NYHA II/III/IV;
- Must be able to be enrolled within 48h from admission to the hospital;
- Body weight 50 - 120 kg;
- Able and willing to provide informed written consent and written documentation of informed consent.
Who cannot join
- NYHA Class I;
- Dyspnea primarily due to non-cardiac causes;
- Clinical diagnosis of acute coronary syndrome, planned PCI, life-threatening arrhythmias, planned ICD/CRT, planned cardiac surgery;
- Recent CABG and PCI in the last 3 months;
- Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy, congenital disease, uncorrected primary valve disease needing cardiac surgery;
- Ongoing or planned treatment with ultrafiltration or dialysis;
Show all 21Show fewer
- Patients that required cardiopulmonary resuscitation in the last 4 weeks prior to enrollment;
- Systolic blood pressure at enrolment <100 mmHg or >180 mmHg;
- Current (within 2h prior to screening) need of cardiac/respiratory mechanical support;
- Severe pulmonary disease with chronic oxygen need at home or history of COPD >GOLD III, IPF or Bronchial Asthma;
- Any condition or therapy, which would make the patient unsuitable for the study, or life expectancy less than 12 months (e.g. active malignancy);
- Impaired renal function with eGFR <30 ml/min/1.73 m² calculated by Modification of Diet in Renal Disease [MDRD] formula;
- Anemia (Hb <9 g/L or hematocrit <25%);
- Temperature >38°C (oral or equivalent) or sepsis or active infection requiring IV antimicrobial treatment;
- Hepatic insufficiency classified as Child-Pugh B or C;
- Any organ transplant recipient, or patient currently listed for transplant or admitted for any transplantation;
- Major surgery within 30 days;
- Unwilling or unable to be fully evaluated for all follow-up assessments;
- Participation in an interventional clinical trial involving another investigational drug or an implantable medical device within 4 weeks prior to inclusion;
- Women of child bearing potential or women who are pregnant or breast-feeding or are not using adequate contraceptive methods [i.e. orally administered hormonal contraceptives, surgical intervention (tubal ligation), intrauterine device (IUD) and sexual abstinence];
- Male patients with reproductive potential who refuse adequate means of contraception during and up to 3 months after end of infusion of HAM8101 (Adrecizumab).
Trial locations and contacts
2 sites in 1 country.
Indonesia2 sites, 2 recruiting
- Recruiting
RSUD Dr. Saiful Anwar Malang
Malang
Saifur Rohman, ippoenk@yahoo.com
- Recruiting
Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada
Yogyakarta, 55281
Anggoro Budi Hartopo, (+62)274 631011, a_bhartopo@ugm.ac.id
About this study
Official title: A Dose Escalation Evaluation of Safety and Tolerability of Adrecizumab - a Humanized Monoclonal Antibody Against Adrenomedullin (ADM) in Patients With Acute Heart Failure Requiring Hospitalization
This is an open, standard therapy controlled clinical trial using a single intravenous infusion of HAM8101 (Adrecizumab) in patients hospitalized for AHF. This study will serve as a safety trial for HAM8101 (Adrecizumab) in AHF, using a dose escalating design.
Acute Heart Failure (AHF), both as deterioration of chronic stable condition or "de novo" onset constitutes a major indication of particular interest and continues to be a major health problem, with millions of people being affected, still associated with high mortality and rehospitalization rates despite numerous attempts to improve the situation.
Read more
It is believed that deteriorated vascular integrity and function, which manifests in various symptoms resulting from extravasation of fluid and solutes, is a key mechanism contributing to development and progression of the disease.
Therefore, it is warranted to start a phase 2 safety and proof of concept study with a new investigational product (IMP) that enhances the plasma concentration of bio-ADM in the circulation to restore and stabilize the vascular integrity and function in patients with AHF after initial stabilization with the current standard of care (SoC).
Read the detailed description
The objectives of this study are to determine the safety/tolerability together with PD parameters of an intravenous slow infusion of 3 increasing doses of HAM8101 (Adrecizumab) in patients with AHF in a Phase IIa safety clinical trial. Efficacy of HAM8101 (Adrecizumab) will be explored secondarily.
The primary objective of this trial is to evaluate safety and tolerability of increasing doses of HAM8101 (Adrecizumab) in patients with AHF. Treatment emergent SAEs will be collected and carefully monitored on a continuous basis during the in-hospital stay and the 3-month follow-up after discharge. Treatment emergent AEs will be collected and monitored on a continuous basis during the in-hospital stay. Plasma and urine specimens will be collected daily from the first day of treatment until hospital discharge for routine safety assessments and to evaluate renal function.
All subjects will receive phone calls 30 (±7) days from start of study drug infusion to assess the occurrence of adverse events and serious adverse events, mortality and hospital readmission for HF or renal dysfunction. Patients will be contacted again 60 (±14) days and 90 (±14) days after infusion of HAM8101 (Adrecizumab) to document survival and episodes of re-hospitalization.
The study is designed primarily to understand the safety and tolerability of increasing doses of HAM8101 (Adrecizumab) in AHF patients (NYHA class II-IV) already in treatment and hemodynamically stabilized with a therapy that represents the standard of care (SoC) as recommended by international ESC 2016 Guidelines and it comprises 3 different patient "cohorts" with each cohort receiving one of 3 escalating doses of HAM8101 (Adrecizumab).
In addition, the study will provide a PD profile of HAM8101 (Adrecizumab) in AHF, in this acute condition.
After signing an Institutional Review Board approved Informed Consent Form, subjects will be asked to undergo screening procedures for study eligibility. Patients will be prescreened by site staff based on potential entry criteria as soon as possible after admission. Upon confirmation of eligibility and informed consent signature, the patient will receive the study drug within 48h from hospital admission. All patients will be evaluated daily during the hospitalization. In-hospital assessments of symptoms and signs of residual congestion (as composite congestion score) will be made daily from start of study drug infusion and up to Day 7, unless a patient is discharged earlier or later or dies earlier than Day 7. After discharge patients will be followed up for an additional 3 months for safety assessments with telephone contacts at months 1, 2, and 3, to document survival and episodes of re-hospitalization.
Thirty (30) patients with AHF (NYHA class II-IV) will be enrolled into 3 sequential experimental cohorts during the inpatient setting: 0.5 mg/kg, 2 mg/kg and 8 mg/kg of HAM8101 (Adrecizumab).
A control group of 10 patients with AHF will receive only standard of care treatment and will be monitored during the inpatient and outpatient settings.
- Conditions
- Acute Heart Failure
- Being tested
- Adrecizumab
- Keywords
- Acute heart failure treatment Adrecizumab Safety
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdrecizumabDrug
Also called HAM8101 (Adrecizumab)
HAM8101 (Adrecizumab) is a humanized IgG1 monoclonal antibody (mAb).
| Study group | Role | What they receive |
|---|---|---|
| HAM8101 (Adrecizumab) : 0.5 mg/kg | Experimental | HAM8101 (Adrecizumab) : 0.5 mg/kg Receives: Drug: Adrecizumab |
| HAM8101 (Adrecizumab) : 2 mg/kg | Experimental | HAM8101 (Adrecizumab) : 2 mg/kg Receives: Drug: Adrecizumab |
| HAM8101 (Adrecizumab) : 8 mg/kg | Experimental | HAM8101 (Adrecizumab) : 8 mg/kg Receives: Drug: Adrecizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-emergent Serious Adverse Events (SAEs) during the hospitalization period
Measured: 7 days
Secondary outcomes (1)
In-hospital assessment of AHF
Change in signs and symptoms of AHF assessed at 30min, 1h, 6h, 12h, 24h from onset of test dose and daily through day 7 - or until discharge from hospital if this occurs earlier or later than 7 days. For "change" is intended a change in severity of considered signs and symptoms (e.g. shift from moderate to mild or vice versa, etc) symptoms (such as breathlessness, ankle swelling, and fatigue) and signs (e.g. raised jugular venous pressure, pulmonary crackles, peripheral edema, heart gallop sounds and or murmurs, oliguria)
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start15 Dec 2019
- Primary completion31 Dec 2021 (estimated)
- Study completion31 Mar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Heart FailureStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- GREAT Network Italy
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Salvatore Di Somma, Study director, GREAT Network Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04252937
- Sponsor's protocol ID
- Adeste Study
- Acronym
- ADESTE
- Status last verified
- Mar 2021
- First submitted
- 20 Jan 2020
- Last updated
- 9 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to make IPD available
Publications
Geven C, Pickkers P. The mechanism of action of the adrenomedullin-binding antibody adrecizumab. Crit Care. 2018 Jun 13;22(1):159. doi: 10.1186/s13054-018-2074-1. No abstract available.
PubMed 29895302Geven C, van Lier D, Blet A, Peelen R, Ten Elzen B, Mebazaa A, Kox M, Pickkers P. Safety, tolerability and pharmacokinetics/pharmacodynamics of the adrenomedullin antibody adrecizumab in a first-in-human study and during experimental human endotoxaemia in healthy subjects. Br J Clin Pharmacol. 2018 Sep;84(9):2129-2141. doi: 10.1111/bcp.13655. Epub 2018 Jul 3.
PubMed 29856470Ambrosy AP, Pang PS, Khan S, Konstam MA, Fonarow GC, Traver B, Maggioni AP, Cook T, Swedberg K, Burnett JC Jr, Grinfeld L, Udelson JE, Zannad F, Gheorghiade M; EVEREST Trial Investigators. Clinical course and predictive value of congestion during hospitalization in patients admitted for worsening signs and symptoms of heart failure with reduced ejection fraction: findings from the EVEREST trial. Eur Heart J. 2013 Mar;34(11):835-43. doi: 10.1093/eurheartj/ehs444. Epub 2013 Jan 4.
PubMed 23293303
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Escalation Evaluation of Safety and Tolerability of Adrecizumab - a Humanized Monoclonal Antibody Against Adrenomedullin (ADM) in Patients With Acute Heart Failure Requiring Hospitalization
- ClinicalTrials.gov ID
- NCT04252937
- Acronym / sponsor ID
- ADESTE / Adeste Study
- Conditions
- Acute Heart Failure
- Keywords
- Acute heart failure treatment Adrecizumab Safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- GREAT Network ItalyResearch network
- Study start
- 15 Dec 2019 (actual)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 31 Mar 2022 (estimated)
- First posted
- 5 Feb 2020 (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.
This is an open, standard therapy controlled clinical trial using a single intravenous infusion of HAM8101 (Adrecizumab) in patients hospitalized for AHF. This study will serve as a safety trial for HAM8101 (Adrecizumab) in AHF, using a dose escalating design.
Acute Heart Failure (AHF), both as deterioration of chronic stable condition or "de novo" onset constitutes a major indication of particular interest and continues to be a major health problem, with millions of people being affected, still associated with high mortality and rehospitalization rates despite numerous attempts to improve the situation.
It is believed that deteriorated vascular integrity and function, which manifests in various symptoms resulting from extravasation of fluid and solutes, is a key mechanism contributing to development and progression of the disease.
Therefore, it is warranted to start a phase 2 safety and proof of concept study with a new investigational product (IMP) that enhances the plasma concentration of bio-ADM in the circulation to restore and stabilize the vascular integrity and function in patients with AHF after initial stabilization with the current standard of care (SoC).
Detailed description
The objectives of this study are to determine the safety/tolerability together with PD parameters of an intravenous slow infusion of 3 increasing doses of HAM8101 (Adrecizumab) in patients with AHF in a Phase IIa safety clinical trial. Efficacy of HAM8101 (Adrecizumab) will be explored secondarily.
The primary objective of this trial is to evaluate safety and tolerability of increasing doses of HAM8101 (Adrecizumab) in patients with AHF. Treatment emergent SAEs will be collected and carefully monitored on a continuous basis during the in-hospital stay and the 3-month follow-up after discharge. Treatment emergent AEs will be collected and monitored on a continuous basis during the in-hospital stay. Plasma and urine specimens will be collected daily from the first day of treatment until hospital discharge for routine safety assessments and to evaluate renal function.
All subjects will receive phone calls 30 (±7) days from start of study drug infusion to assess the occurrence of adverse events and serious adverse events, mortality and hospital readmission for HF or renal dysfunction. Patients will be contacted again 60 (±14) days and 90 (±14) days after infusion of HAM8101 (Adrecizumab) to document survival and episodes of re-hospitalization.
The study is designed primarily to understand the safety and tolerability of increasing doses of HAM8101 (Adrecizumab) in AHF patients (NYHA class II-IV) already in treatment and hemodynamically stabilized with a therapy that represents the standard of care (SoC) as recommended by international ESC 2016 Guidelines and it comprises 3 different patient "cohorts" with each cohort receiving one of 3 escalating doses of HAM8101 (Adrecizumab).
In addition, the study will provide a PD profile of HAM8101 (Adrecizumab) in AHF, in this acute condition.
After signing an Institutional Review Board approved Informed Consent Form, subjects will be asked to undergo screening procedures for study eligibility. Patients will be prescreened by site staff based on potential entry criteria as soon as possible after admission. Upon confirmation of eligibility and informed consent signature, the patient will receive the study drug within 48h from hospital admission. All patients will be evaluated daily during the hospitalization. In-hospital assessments of symptoms and signs of residual congestion (as composite congestion score) will be made daily from start of study drug infusion and up to Day 7, unless a patient is discharged earlier or later or dies earlier than Day 7. After discharge patients will be followed up for an additional 3 months for safety assessments with telephone contacts at months 1, 2, and 3, to document survival and episodes of re-hospitalization.
Thirty (30) patients with AHF (NYHA class II-IV) will be enrolled into 3 sequential experimental cohorts during the inpatient setting: 0.5 mg/kg, 2 mg/kg and 8 mg/kg of HAM8101 (Adrecizumab).
A control group of 10 patients with AHF will receive only standard of care treatment and will be monitored during the inpatient and outpatient settings.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| HAM8101 (Adrecizumab) : 0.5 mg/kg | Experimental | Drug: AdrecizumabHAM8101 (Adrecizumab) : 0.5 mg/kg |
| HAM8101 (Adrecizumab) : 2 mg/kg | Experimental | Drug: AdrecizumabHAM8101 (Adrecizumab) : 2 mg/kg |
| HAM8101 (Adrecizumab) : 8 mg/kg | Experimental | Drug: AdrecizumabHAM8101 (Adrecizumab) : 8 mg/kg |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥ 18 years;
- Hospitalization due to the primary diagnosis of AHF, based on ESC 2016 Guidelines;
- NYHA II/III/IV;
- Must be able to be enrolled within 48h from admission to the hospital;
- Body weight 50 - 120 kg;
Key exclusion criteria (21 listed)
- NYHA Class I;
- Dyspnea primarily due to non-cardiac causes;
- Clinical diagnosis of acute coronary syndrome, planned PCI, life-threatening arrhythmias, planned ICD/CRT, planned cardiac surgery;
- Recent CABG and PCI in the last 3 months;
- Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy, congenital disease, uncorrected primary valve disease needing cardiac surgery;
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 |
|---|---|---|
| AdrecizumabAlso: HAM8101 (Adrecizumab)HAM8101 (Adrecizumab) is a humanized IgG1 monoclonal antibody (mAb). | Drug | HAM8101 (Adrecizumab) : 0.5 mg/kg, HAM8101 (Adrecizumab) : 2 mg/kg, HAM8101 (Adrecizumab) : 8 mg/kg |
Primary outcome
Incidence of Treatment-emergent Serious Adverse Events (SAEs) during the hospitalization period
Time frame: 7 days
1 secondary outcome
In-hospital assessment of AHF
Time frame: 7 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2021.
- Background: PubMed 29895302Geven C, Pickkers P. The mechanism of action of the adrenomedullin-binding antibody adrecizumab. Crit Care. 2018 Jun 13;22(1):159. doi: 10.1186/s13054-018-2074-1. No abstract available.
- Background: PubMed 29856470Geven C, van Lier D, Blet A, Peelen R, Ten Elzen B, Mebazaa A, Kox M, Pickkers P. Safety, tolerability and pharmacokinetics/pharmacodynamics of the adrenomedullin antibody adrecizumab in a first-in-human study and during experimental human endotoxaemia in healthy subjects. Br J Clin Pharmacol. 2018 Sep;84(9):2129-2141. doi: 10.1111/bcp.13655. Epub 2018 Jul 3.
- Background: PubMed 23293303Ambrosy AP, Pang PS, Khan S, Konstam MA, Fonarow GC, Traver B, Maggioni AP, Cook T, Swedberg K, Burnett JC Jr, Grinfeld L, Udelson JE, Zannad F, Gheorghiade M; EVEREST Trial Investigators. Clinical course and predictive value of congestion during hospitalization in patients admitted for worsening signs and symptoms of heart failure with reduced ejection fraction: findings from the EVEREST trial. Eur Heart J. 2013 Mar;34(11):835-43. doi: 10.1093/eurheartj/ehs444. Epub 2013 Jan 4.
- Individual participant dataSharing planned: No. There is no plan to make IPD available
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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.
Salvatore Di Somma study director
GREAT Network Italy
2 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 in people with Acute Heart Failure, run by GREAT Network Italy at 2 sites in Indonesia.
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 21 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: status not confirmed, as of the sponsor's last update on 9 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Indonesia. 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. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Salvatore Di Somma (00393483316131, salvatore.disomma@uniroma1.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-emergent Serious Adverse Events (SAEs) during the hospitalization period (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04252937, which also lists 3 linked publications.
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 9 Mar 2021.