Immunomodulation of EA-230 Following On-pump Coronary Artery Bypass Grafting (CABG)

NCT03145220 | Unknown Phase 2 DMC

• 2 other identifiers: EASI-Study2015-005600-28
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

EA-230 is a newly developed synthetic compound with anti-inflammatory properties, it is a linear tetrapeptide derived from the human chorionic gonadotropin hormone (hCG). Recently, its immunomodulatory effects in humans were confirmed in a phase I trial and an optimal dose was established. To establish this anti-inflammatory effect in a selected patient population and assess clinical outcome, a combined phase IIa/IIb trial will be conducted with patients undergoing cardiac surgery.

Conditions

Systemic Inflammatory Response Syndrome; Coronary Artery Bypass Grafting

Keywords

EA-230; Systemic Inflammatory Response Syndrome; Acute Kidney Injury; Interleukin-6; Safety; Tolerability; Phase II; Randomized clinical trial

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability (treatment related (serious) adverse events)

  Safety and tolerability expressed in treatment related (serious) adverse events

  Total (serious) adverse events related to treatment at day 90 after treatment

• Interleukin-6 (IL-6)

  Blood plasma levels IL-6

  1 day: at baseline, start of the cardiopulmonary bypass (CPB), stop of CPB, 2h after stop of CPB, 4h after stop of CPB, 6h after stop of CPB and first post-operative day.

Secondary Outcomes (4)

• Glomerular filtration rate (GFR)

  Up to 3 days. At the day before surgery (baseline) and at the morning of the first post-operative day

• Urine kidney injury markers (KIM-1, NGAL, L-FABP, TIMP-2*IGFBP-7, urinary IL-18, NAG, creatine, urea, albumin)

  Up to1 day: at baseline (before surgery), 2h after stop of CPB, 4h after stop of CPB, 6h after stop of CPB and first post-operative day.

• Other cytokines/chemokines (TNFα, IL-8, IL-10, IL-1RA, MCP-1, MIP1α, MIP1β, VCAM, ICAM, IL-17A)

  Up to 1 day: at baseline, start of the cardiopulmonary bypass (CPB), stop of CPB, 2h after stop of CPB, 4h after stop of CPB, 6h after stop of CPB and first post-operative day.

• Leukocyte counts (differentiated)

  Up to 1 day: at baseline, start of the cardiopulmonary bypass (CPB), stop of CPB, 2h after stop of CPB, 4h after stop of CPB, 6h after stop of CPB and first post-operative day.

Other Outcomes (27)

• Heart rate

  First 24 post-operative hours, mean values per 30 minutes.

• Blood pressure

  First 24 post-operative hours, mean values per 30 minutes.

• body temperature

  First 24 post-operative hours, measured with an interval of 2 hours.

Study Arms (2)

EA-230

ACTIVE COMPARATOR

Intravenous infusion of EA-230, 90 mg/kg/hour. Administered from start of surgical incision until stoppage of the cardio-pulmonary bypass pump, for a maximum of 4 hours.

Drug: EA-230

Placebo

PLACEBO COMPARATOR

Intravenous infusion of NaCl (equivalent osmolarity with active intervention EA-230). Administered from start of surgical incision until stoppage of the cardio-pulmonary bypass pump, for a maximum of 4 hours.

Other: Placebo (NaCl)

Interventions

EA-230 DRUG

Active intervention

Also known as: AQGV

EA-230

Placebo (NaCl) OTHER

Placebo intervention

Also known as: NaCl

Placebo

Eligibility Criteria

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

You may qualify if:

• Patients scheduled for elective on-pump CABG surgery.
• Part 1: 60 patients undergoing CABG surgery, of which circa 40 low risk patients without valve replacement (range: 35-45)
• Part 2: CABG surgery with or without valve replacement
• Written informed consent to participate in this trial prior to any study-mandated procedure.
• Patients aged \>18, both male and female.
• Patients have to agree to use a reliable way of contraception with their partners from study entry until 3 months after study drug administration.

You may not qualify if:

• Immunocompromised
• Solid organ transplantation
• Known HIV
• Pregnancy
• Systemic use of immunosuppressive drugs
• Non-elective/Emergency surgery
• Hematological disorders
• Known disorders from myeloid and/or lymphoid origin
• Leucopenia (leucocyte count \< 4x109/L)
• Known hypersensitivity to any excipients of the drug formulations used
• Treatment with investigational drugs or participation in any other intervention clinical trial within 30 days prior to study drug administration
• Inability to personally provide written informed consent (e.g. for linguistic or mental reasons)
• Known or suspected of not being able to comply with the trial protocol.
• In addition, for part 1 only (to select low-risk patients):
• Euroscore II \<4

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Exponential Biotherapies Inc.: collaborator

Study Sites (1)

Intensive care, research unit, Radboud University Medical Centre

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Related Publications (2)

• van Groenendael R, Beunders R, Hemelaar P, Hofland J, Morshuis WJ, van der Hoeven JG, Gerretsen J, Wensvoort G, Kooistra EJ, Claassen WJ, Waanders D, Lamberts MGA, Buijsse LSE, Kox M, van Eijk LT, Pickkers P. Safety and Efficacy of Human Chorionic Gonadotropin Hormone-Derivative EA-230 in Cardiac Surgery Patients: A Randomized Double-Blind Placebo-Controlled Study. Crit Care Med. 2021 May 1;49(5):790-803. doi: 10.1097/CCM.0000000000004847.

  PMID: 33591006 DERIVED

• van Groenendael R, Beunders R, Hofland J, Morshuis WJ, Kox M, van Eijk LT, Pickkers P. The Safety, Tolerability, and Effects on the Systemic Inflammatory Response and Renal Function of the Human Chorionic Gonadotropin Hormone-Derivative EA-230 Following On-Pump Cardiac Surgery (The EASI Study): Protocol for a Randomized, Double-Blind, Placebo-Controlled Phase 2 Study. JMIR Res Protoc. 2019 Feb 6;8(2):e11441. doi: 10.2196/11441.

  PMID: 30724734 DERIVED

MeSH Terms

Conditions

Systemic Inflammatory Response Syndrome; Acute Kidney Injury

Interventions

alanyl-glutaminyl-glycyl-valine

Condition Hierarchy (Ancestors)

Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: prof. dr.

Study Record Dates

• First Submitted: June 22, 2016
• First Posted: May 9, 2017
• Study Start: June 1, 2016
• Primary Completion: October 1, 2018
• Study Completion: October 1, 2018
• Last Updated: June 26, 2018

Record last verified: 2018-06

Locations

NL (1)