Efficacy and Safety of RMC-035 in Subjects at High Risk for Acute Kidney Injury Following Open-Chest Cardiac Surgery

NCT ID: NCT05126303

Last Updated: 2024-05-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 177 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-31
• Study Completion Date: 2023-07-12

Brief Summary

This study evaluates RMC-035 compared to placebo for the prevention of acute kidney injury (AKI) in subjects who are at high risk for AKI following cardiac surgery. Half of the subjects will receive RMC-035 and the other half will receive placebo.

Detailed Description

This is a Phase 2, randomized, double-blind, adaptive, parallel group clinical study that will evaluate RMC-035 compared to placebo in subjects at high risk for acute kidney injury (AKI) following cardiac surgery. Subjects are randomized in a 1:1 ratio.

Conditions

Acute Kidney Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

RMC-035

RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration.

Dosing will be based on renal function at Day -1: Subjects with eGFR ≥60 mL/min/1.73m2 will receive 1.3 mg/kg (per dose) for the first and second dose, followed by 0.65 mg/kg (per dose) for the third, fourth and fifth dose, while subjects with eGFR >30 and <60 mL/min/1.73m2 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours.

Group Type: EXPERIMENTAL

RMC-035

Intervention Type: DRUG

Concentrate for Solution for Infusion

Placebo

Identical to RMC-035 arm except that the placebo contains no active ingredient.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Concentrate for Solution for Infusion

Interventions

RMC-035

Concentrate for Solution for Infusion

Intervention Type: DRUG

Placebo

Concentrate for Solution for Infusion

Intervention Type: DRUG

Other Intervention Names

ROSgard

Eligibility Criteria

Inclusion Criteria

1. Institutional Review Board/ International Ethics Committee approved Informed Consent obtained

2. Ability to understand and comply with the study requirements and able to provide written informed consent

3. Age ≥18 and <85 years

4. Estimated glomerular filtration rate (eGFR) is ≥30 mL/min/1.73 m2

5. Subject is scheduled for non-emergent coronary artery bypass grafting (CABG) surgery and/or valve surgery and/or ascending aorta aneurysm surgery with use of cardiopulmonary bypass (CPB), and AKI risk factors are present at screening

6. Female subject is not of child-bearing potential, or agreeing not to become pregnant

7. Female subject must not be breastfeeding

8. Female subject must not donate ova

9. Male subject and their female spouse/partner(s) who are of childbearing potential must be using a highly effective form of birth control

10. Male subjects must not donate sperm

11. Subject agrees not to participate in another interventional study

Exclusion Criteria

1. Medical condition that makes the subject unsuitable for study participation

2. Scheduled for emergent surgeries (eg, aortic dissection)

3. Scheduled for CABG and/or valve surgery and/or ascending aorta aneurysm surgery combined with additional non-emergent cardiac surgeries (eg, congenital heart defects)

4. Scheduled to undergo transcatheter aortic valve implantation (TAVI) or transcatheter aortic valve replacement (TAVR), or off-pump surgeries or left ventricular assist device (LVAD) implantation

5. Experiences a cardiogenic shock or hemodynamic instability which require inotropes or vasopressors or other mechanical devices within 24 hours prior to surgery

6. Requirement for defibrillator or permanent pacemaker, mechanical ventilation, intraaortic balloon pumping (IABP), LVAD, or other forms of mechanical circulatory support (MCS)

7. Diagnosed with AKI (as defined by KDIGO criteria) within 3 months prior to surgery

8. Required cardiopulmonary resuscitation within 14 days prior to cardiac surgery

9. Ongoing sepsis or an untreated diagnosed clinically significant infection (viral or bacterial)

10. Total bilirubin or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2 times the upper limit of normal (ULN)

11. History of solid organ transplantation

12. History of renal replacement therapy (RRT)

13. Medical condition which requires active immunosuppressive treatment

14. Severe allergic asthma

15. Ongoing chemotherapy or radiation therapy for malignancy that may have an impact on kidney function

16. Received an investigational medicinal product within the last 90 days (or within 5 half-lives of the investigational drug, whichever is longer)

17. Subject has a known allergy to RMC-035 or one of its constituents, or has previously received RMC-035

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 84 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guard Therapeutics AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tobias Agervald, MD

Role: STUDY_DIRECTOR

Guard Therapeutics

Alexander Zarbock, MD

Role: PRINCIPAL_INVESTIGATOR

Muenster University Hospital

Locations

Indiana Ohio Heart

Fort Wayne, Indiana, United States

Bryan Heart

Lincoln, Nebraska, United States

Rochester Regional Health - Rochester General Hospital

Rochester, New York, United States

Duke University Hospital

Durham, North Carolina, United States

Baylor Scott and White Research Institute - Dallas

Dallas, Texas, United States

University of Virginia (UVA) Health - University Hospital

Charlottesville, Virginia, United States

University of Wisconsin

Madison, Wisconsin, United States

Aurora Health Care - Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Hamilton Health Sciences

Hamilton, , Canada

CHUM

Montreal, , Canada

MUHC - Royal Victoria Hospital

Montreal, , Canada

Institut Universitaire de Cardiologie et de Pneumologie de Québec

Québec, , Canada

St. John Regional Hospital

Saint John, , Canada

Saint Michael's Hospital

Toronto, , Canada

University Hospital Hradec Kralove

Hradec Králové, , Czechia

University Hospital Motol - Charles University Prague

Prague, , Czechia

Herz- und Diabeteszentrum Nordrhein-Westfalen (NRW)

Bad Oeynhausen, , Germany

Universitätsklinikum Köln

Cologne, , Germany

Herzzentrum Dresden GmbH

Dresden, , Germany

Westdeutsches Herzzentrum Essen

Essen, , Germany

Universitätsklinikum Giessen und Marburg - Standort Giessen

Giessen, , Germany

Universitätsklinikum Halle (Saale)

Halle, , Germany

Deutsches Herzzentrum München

München, , Germany

Münster University Hospital

Münster, , Germany

Hospital Sant Pau

Barcelona, , Spain

Reina Sofia University Hospital

Córdoba, , Spain

Hospital de La Princesa

Madrid, , Spain

Hospital Universitario Central de Asturias

Oviedo, , Spain

Complejo Hospitalario Universitario de Santiago (CHUS)

Santiago de Compostela, , Spain

Countries

United States; Canada; Czechia; Germany; Spain

References

Zarbock A, Larsson TE, Noiseux N, Mazer CD, Bohm J, Laflamme M, Matschke K, Burkert J, de Varennes B, Myjavec A, Boning A, Koyner JL, Engelman D, Reusch M, Thielmann M; AKITA investigators. Efficacy and safety of therapeutic alpha-1-microglobulin RMC-035 in reducing kidney injury after cardiac surgery: a multicentre, randomised, double-blind, parallel group, phase 2a trial. EClinicalMedicine. 2024 Sep 16;76:102830. doi: 10.1016/j.eclinm.2024.102830. eCollection 2024 Oct.

Reference Type: DERIVED

PMID: 39318788 (View on PubMed)

Mazer CD, Siadati-Fini N, Boehm J, Wirth F, Myjavec A, Brown CD, Koyner JL, Boening A, Engelman DT, Larsson TE, Renfurm R, de Varennes B, Noiseux N, Thielmann M, Lamy A, Laflamme M, von Groote T, Ronco C, Zarbock A. Study protocol of a phase 2, randomised, placebo-controlled, double-blind, adaptive, parallel group clinical study to evaluate the efficacy and safety of recombinant alpha-1-microglobulin in subjects at high risk for acute kidney injury following open-chest cardiac surgery (AKITA trial). BMJ Open. 2023 Apr 6;13(4):e068363. doi: 10.1136/bmjopen-2022-068363.

Reference Type: DERIVED

PMID: 37024249 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

21-ROS-05

Identifier Type: -

Identifier Source: org_study_id