Adrecizumab Dose Escalation Safety and Tolerability Evaluation (ADESTE)

  • STATUS
    Recruiting
  • End date
    Mar 31, 2022
  • participants needed
    30
  • sponsor
    GREAT Network Italy
Updated on 17 March 2021

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.

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).

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.

Details
Condition Acute Heart Failure
Treatment Adrecizumab
Clinical Study IdentifierNCT04252937
SponsorGREAT Network Italy
Last Modified on17 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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

Exclusion Criteria

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
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 m calculated by Modification of Diet in Renal Disease [MDRD] formula
Anemia (Hb <9 g/L or hematocrit <25%)
Temperature >38C (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)
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note