Adrecizumab Dose Escalation Safety and Tolerability Evaluation (ADESTE)

NCT04252937 | Unknown Phase 2 DMC

• 1 other identifier: Adeste Study
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Acute Heart Failure

Keywords

Acute heart failure treatment Adrecizumab Safety

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-emergent Serious Adverse Events (SAEs) during the hospitalization period

  7 days

Secondary Outcomes (1)

• In-hospital assessment of AHF

  7 days

Study Arms (3)

HAM8101 (Adrecizumab) : 0.5 mg/kg

EXPERIMENTAL

HAM8101 (Adrecizumab) : 0.5 mg/kg

Drug: Adrecizumab

HAM8101 (Adrecizumab) : 2 mg/kg

EXPERIMENTAL

HAM8101 (Adrecizumab) : 2 mg/kg

Drug: Adrecizumab

HAM8101 (Adrecizumab) : 8 mg/kg

EXPERIMENTAL

HAM8101 (Adrecizumab) : 8 mg/kg

Drug: Adrecizumab

Interventions

Adrecizumab DRUG

HAM8101 (Adrecizumab) is a humanized IgG1 monoclonal antibody (mAb).

Also known as: HAM8101 (Adrecizumab)

HAM8101 (Adrecizumab) : 0.5 mg/kg; HAM8101 (Adrecizumab) : 2 mg/kg; HAM8101 (Adrecizumab) : 8 mg/kg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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;

Sponsors & Collaborators

• GREAT Network Italy: lead

Study Sites (2)

RSUD Dr. Saiful Anwar Malang

Malang, Indonesia

RECRUITING

Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada

Yogyakarta, 55281, Indonesia

RECRUITING

Related Publications (3)

• 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.

  PMID: 29895302 BACKGROUND

• Geven 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.

  PMID: 29856470 BACKGROUND

• Ambrosy 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.

  PMID: 23293303 BACKGROUND

MeSH Terms

Interventions

enibarcimab

Study Officials

• Salvatore Di Somma

  GREAT Network Italy

  STUDY DIRECTOR

Central Study Contacts

Salvatore Di Somma

CONTACT

00393483316131; salvatore.disomma@uniroma1.it

Paola Vietti

CONTACT

00393316703662; paola.vietti@greatnetwork.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2020
• First Posted: February 5, 2020
• Study Start: December 15, 2019
• Primary Completion: December 31, 2021
• Study Completion: March 31, 2022
• Last Updated: March 9, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

ID (2)