Treatment of Patients With Early Septic Shock and Bio-Adrenomedullin(ADM) Concentration > 70 pg/ml With ADRECIZUMAB

NCT03085758 | Completed Phase 2 Results DMC

• 1 other identifier: ADR-02
• Study Type: interventional
• Target: 301
• Locations: 4 countries
• Sites: 30

Brief Summary

This is a double-blind, placebo-controlled, randomized, multicenter proof of concept and dose-finding phase II study using two doses of ADRECIZUMAB in patients with early septic shock and a bio-ADM plasma concentration at admission of \> 70 pg/ml.

Conditions

Septic Shock

Keywords

Early Septic Shock

Outcome Measures

Primary Outcomes (6)

• Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Mortality)

  The endpoints for the primary objective is mortality evaluated over the 90 days study period.

  90 days

• Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Interruption of Infusion)

  The endpoints for the primary objective are to determine over the 90 days study period: Interruption of infusion due to intolerability of ADRECIZUMAB

  90 days

• Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Frequency of TEAEs)

  The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group.

  90 days

• Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Mild Severity

  The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with mild severity treatment emergent events.

  90 days

• Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Moderate Severity

  The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with moderate severity treatment emergent events.

  90 days

• Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Severe Severity

  The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with severe severity treatment emergent events.

  90 days

Secondary Outcomes (27)

• Efficacy to be Determined by Sepsis Support Index (SSI)

  14 days

• Sepsis Support Index (SSI)

  28 days

• Penalized Sepsis Support Index (pSSI) at 14 Day Follow-up

  day 14

• Persistent Organ Dysfunction or Death at 14 and 28 Day Follow-up

  day 14 and day 28

• Mortality Rate

  day 28

Other Outcomes (6)

• In Sub-study Key Pharmacokinetic Parameters Peak Plasma Concentrations (Cmax) Are to be Determined in 80 Patients

  28 days

• In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients

  28 days

• In Sub-study Key Pharmacokinetic Parameter AUC is to be Determined in 80 Patients

  28 days

Study Arms (3)

Treatment Arm A

EXPERIMENTAL

Intravenous infusion over approximately 1 hour of single i.v. dose of 2 mg/kg Adrecizumab (treatment arm A)

Biological: Adrecizumab

Treatment Arm B

EXPERIMENTAL

Intravenous infusion over approximately 1 hour of single i.v. dose of 4 mg/kg Adrecizumab (treatment arm B)

Biological: Adrecizumab

Control group

PLACEBO COMPARATOR

Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab (control group)

Biological: Placebo

Interventions

Adrecizumab BIOLOGICAL

Single i.v. dose of 2 mg/kg (treatment arm A) or 4 mg/kg (treatment arm B)

Treatment Arm A; Treatment Arm B

Placebo BIOLOGICAL

Single i.v. dose of placebo (control group)

Control group

Eligibility Criteria

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

You may qualify if:

• Written informed consent by patient or legal representative (according to country - specific regulations)
• Male and female patient, age ≥ 18 years
• Body weight 50 kg - 120 kg
• Bio-ADM concentration \> 70 pg/ml
• Patient with early septic shock (start of vasopressor therapy \< 12 hours)
• Women of childbearing potential must have a negative serum or urine pregnancy test before randomization
• Highly effective method of contraception must be maintained for 6 months after study start by women of childbearing potential and sexually active men.
• No care limitation

You may not qualify if:

• Moribund
• Pre-existing unstable condition (e.g. a recent cerebral hemorrhage or infarct, a recent acute unstable myocardial infarction (all \< 3 months), congestive heart failure - New York Heart Association (NYHA) Class IV
• Patients that required cardiopulmonary resuscitation in the last 4 weeks prior to evaluation for enrollment
• Severe Chronic Obstructive Pulmonary Disease (COPD) with chronic oxygen need at home (GOLD IV)
• Any organ or bone marrow transplant within the past 24 weeks
• Uncontrolled serious hemorrhage (≥ 2 units of blood / platelets in the previous 24 hrs.). Patients may be considered for enrollment if bleeding has stopped and patient is otherwise qualified
• Uncontrolled hematological / oncological malignancies
• Absolute neutropenia \< 500 per µL
• Severe chronic liver disease (Child-Pugh C)
• Systemic fungal infection or active tuberculosis
• Neuromuscular disorders that impact breathing / spontaneous ventilation
• Burns \> 30% of body surface
• Plasmapheresis
• Breastfeeding women
• Unwilling or unable to be fully evaluated for all follow-up visits

Sponsors & Collaborators

• Adrenomed AG: lead

Study Sites (30)

Clinique Universitaire Saint-Luc (UCL Bruxelles)

Brussels, 1200, Belgium

Location

Antwerp University Hospital (UZA), Critical Care Medicine

Edegem, 2650, Belgium

Location

Groupe Jolimont, Hospitalier de Jolimont

Haine-Saint-Paul, 7100, Belgium

Location

Clinique St. Pierre, Intensive Care

Ottignies, 1340, Belgium

Location

Medical Intensive Care Medicine, Centre hospital - universitaire

Angers, Cedex, 49933, France

Location

CH Victor Dupouy

Argenteuil, Cedex, 95107, France

Location

Hopital Beaujon; Anesthesie Reanimation

Clichy, Cedex, 92118, France

Location

CHU de Limoges

Limoges, Cedex, 87042, France

Location

CHU de Nantes; Medicine Intensive Reanimation

Nantes, Cedex, 44093, France

Location

CHRU Bretonneau, Medecine Intensive Réanimation

Tours, Cedex, 37044, France

Location

University Hospital of Clermont-Ferrand, Dept. of Perioperative Medicine

Clermont-Ferrand, 63003, France

Location

AP-HP, Hopital Louis Mourier, Réanimation Médicale

Colombes, 92700, France

Location

CHD-Vendée

La Roche-sur-Yon, 85000, France

Location

Hôpital de Bicêtre, Service d'anesthésie-réanimation chirurgicale

Le Kremlin-Bicêtre, 94270, France

Location

Hôpital Lariboisière, Dept. d'Anesthesie

Paris, 75010, France

Location

Hôpital Lariboisière, Réanimation Médicale et Traumatologique

Paris, 75010, France

Location

Hôpital Saint-Louis, Service d'Anesthésie-Réanimation

Paris, 75010, France

Location

Hôpital Européen Georges Pompidou, Service d'Anesthésie-Réanimation Chirurgicale, Université Paris Descartes

Paris, 75015, France

Location

Nouvel Hopital Civil

Strasbourg, 67091, France

Location

Hôpital de Hautepierre , Hôpitaux Universitaires de Strasbourg, Unité de Réanimation Chirurgicale, Service d'Anesthésie-Réanimation Chirurgicale

Strasbourg, 67200, France

Location

Universitätsklinikum Aachen, Klinik für Operative Intensivmedizin

Aachen, 52074, Germany

Location

Universitätsklinikum Hamburg-Eppendorf Klinik für Intensivmedizin

Hamburg, 20246, Germany

Location

Universitätsklinikum Jena Klinik für Anästhesiologie und Intensivmedizin

Jena, 07747, Germany

Location

Universitätsklinikum Münster Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie

Münster, 48149, Germany

Location

Universitätsmedizin Rostock Klinik und Poliklinik für Anästhesiologie und Intensivtherapie

Rostock, 18057, Germany

Location

Gelderse Vallei Hospital, Department of Intensive Care

Ede, 6716 RP, Netherlands

Location

Medisch Spectrum Twente, Department of Intensive Care

Enschede, 7512 KZ, Netherlands

Location

Zuyderland Medical Center, Department of Intensive Care

Heerlen, 6401 CX, Netherlands

Location

Radboud UMC Intensive Care

Nijmegen, 6525 GA, Netherlands

Location

Canisius-Wilhelmina-Ziekenhuis (CWZ), Intensive Care

Nijmegen, 6532 SZ, Netherlands

Location

Related Publications (2)

• Laterre PF, Pickkers P, Marx G, Wittebole X, Meziani F, Dugernier T, Huberlant V, Schuerholz T, Francois B, Lascarrou JB, Beishuizen A, Oueslati H, Contou D, Hoiting O, Lacherade JC, Chousterman B, Pottecher J, Bauer M, Godet T, Karakas M, Helms J, Bergmann A, Zimmermann J, Richter K, Hartmann O, Pars M, Mebazaa A; AdrenOSS-2 study participants. Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial. Intensive Care Med. 2021 Nov;47(11):1284-1294. doi: 10.1007/s00134-021-06537-5. Epub 2021 Oct 4.

  PMID: 34605947 DERIVED

• Geven C, Blet A, Kox M, Hartmann O, Scigalla P, Zimmermann J, Marx G, Laterre PF, Mebazaa A, Pickkers P. A double-blind, placebo-controlled, randomised, multicentre, proof-of-concept and dose-finding phase II clinical trial to investigate the safety, tolerability and efficacy of adrecizumab in patients with septic shock and elevated adrenomedullin concentration (AdrenOSS-2). BMJ Open. 2019 Feb 19;9(2):e024475. doi: 10.1136/bmjopen-2018-024475.

  PMID: 30782906 DERIVED

MeSH Terms

Conditions

Shock, Septic

Interventions

enibarcimab

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Results Point of Contact

• Title: Jens Zimmermann
• Organization: Adrenomed AG

jzimmermann@adrenomed.com

+49 (0) 3302 20 77 810

Study Officials

• Jens Zimmermann, Dr.

  Adrenomed AG

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double Blind, Placebo-Controlled, Randomized, Multicenter Proof of Concept and Dose-Finding Phase II Clinical Trial

Study Record Dates

• First Submitted: February 22, 2017
• First Posted: March 21, 2017
• Study Start: December 12, 2017
• Primary Completion: December 20, 2019
• Study Completion: December 20, 2019
• Last Updated: February 21, 2024
• Results First Posted: March 24, 2021

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (5); BE (4); DE (5); FR (16)