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

NCT05126303 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 21-ROS-05
• Study Type: interventional
• Target: 177
• Locations: 5 countries
• Sites: 29

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.

Conditions

Acute Kidney Injury

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects Developing AKI, as Defined Per Kidney Disease Improving Global Outcomes (KDIGO) Criteria

  Percentage of subjects developing AKI based on Serum Creatinine and/or Urine Output per KDIGO definition

  72 hours

Secondary Outcomes (21)

• Area Under the Curve (AUC) of Serum Creatinine (SCr)

  72 hours

• Duration of AKI

  90 days

• Change in SCr Values Over Time

  90 days

• Peak Cystatin C Value

  7 days

• AUC of Cystatin C

  72 hours

Study Arms (2)

RMC-035

EXPERIMENTAL

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.

Drug: RMC-035

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

RMC-035 DRUG

Concentrate for Solution for Infusion

Also known as: ROSgard

RMC-035

Placebo DRUG

Concentrate for Solution for Infusion

Placebo

Eligibility Criteria

• Age: 18 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Institutional Review Board/ International Ethics Committee approved Informed Consent obtained
• Ability to understand and comply with the study requirements and able to provide written informed consent
• Age ≥18 and \<85 years
• Estimated glomerular filtration rate (eGFR) is ≥30 mL/min/1.73 m2
• 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
• Female subject is not of child-bearing potential, or agreeing not to become pregnant
• Female subject must not be breastfeeding
• Female subject must not donate ova
• Male subject and their female spouse/partner(s) who are of childbearing potential must be using a highly effective form of birth control
• Male subjects must not donate sperm
• Subject agrees not to participate in another interventional study

You may not qualify if:

• Medical condition that makes the subject unsuitable for study participation
• Scheduled for emergent surgeries (eg, aortic dissection)
• Scheduled for CABG and/or valve surgery and/or ascending aorta aneurysm surgery combined with additional non-emergent cardiac surgeries (eg, congenital heart defects)
• 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
• Experiences a cardiogenic shock or hemodynamic instability which require inotropes or vasopressors or other mechanical devices within 24 hours prior to surgery
• Requirement for defibrillator or permanent pacemaker, mechanical ventilation, intraaortic balloon pumping (IABP), LVAD, or other forms of mechanical circulatory support (MCS)
• Diagnosed with AKI (as defined by KDIGO criteria) within 3 months prior to surgery
• Required cardiopulmonary resuscitation within 14 days prior to cardiac surgery
• Ongoing sepsis or an untreated diagnosed clinically significant infection (viral or bacterial)
• Total bilirubin or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2 times the upper limit of normal (ULN)
• History of solid organ transplantation
• History of renal replacement therapy (RRT)
• Medical condition which requires active immunosuppressive treatment
• Severe allergic asthma
• Ongoing chemotherapy or radiation therapy for malignancy that may have an impact on kidney function

Sponsors & Collaborators

• Guard Therapeutics AB: lead

Study Sites (29)

Indiana Ohio Heart

Fort Wayne, Indiana, 48604, United States

Location

Bryan Heart

Lincoln, Nebraska, 68506, United States

Location

Rochester Regional Health - Rochester General Hospital

Rochester, New York, 14621, United States

Location

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

Baylor Scott and White Research Institute - Dallas

Dallas, Texas, 75226, United States

Location

University of Virginia (UVA) Health - University Hospital

Charlottesville, Virginia, 22908, United States

Location

University of Wisconsin

Madison, Wisconsin, 53706, United States

Location

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

Milwaukee, Wisconsin, 53215, United States

Location

Hamilton Health Sciences

Hamilton, Canada

Location

CHUM

Montreal, Canada

Location

MUHC - Royal Victoria Hospital

Montreal, Canada

Location

Institut Universitaire de Cardiologie et de Pneumologie de Québec

Québec, Canada

Location

St. John Regional Hospital

Saint John, Canada

Location

Saint Michael's Hospital

Toronto, Canada

Location

University Hospital Hradec Kralove

Hradec Králové, Czechia

Location

University Hospital Motol - Charles University Prague

Prague, Czechia

Location

Herz- und Diabeteszentrum Nordrhein-Westfalen (NRW)

Bad Oeynhausen, Germany

Location

Universitätsklinikum Köln

Cologne, Germany

Location

Herzzentrum Dresden GmbH

Dresden, Germany

Location

Westdeutsches Herzzentrum Essen

Essen, Germany

Location

Universitätsklinikum Giessen und Marburg - Standort Giessen

Giessen, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, Germany

Location

Deutsches Herzzentrum München

München, Germany

Location

Münster University Hospital

Münster, DE-481 49, Germany

Location

Hospital Sant Pau

Barcelona, Spain

Location

Reina Sofia University Hospital

Córdoba, Spain

Location

Hospital de La Princesa

Madrid, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Spain

Location

Complejo Hospitalario Universitario de Santiago (CHUS)

Santiago de Compostela, Spain

Location

Related Publications (2)

• 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.

  PMID: 39318788 DERIVED

• 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.

  PMID: 37024249 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Limitations and Caveats

Study was stopped prematurely for futility following Data Monitoring Committee (DMC) recommendation. The early termination lead to smaller numbers than planned, and that not all outcome measures were analyzed.

Results Point of Contact

• Title: Sara Thuresson, Head of Clinical Operations
• Organization: Guard Therapeutics

sara.thuresson@guardtherapeutics.com

+46733319438

Study Officials

• Tobias Agervald, MD

  Guard Therapeutics

  STUDY DIRECTOR

• Alexander Zarbock, MD

  Muenster University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, adaptive, parallel group

Study Record Dates

• First Submitted: November 8, 2021
• First Posted: November 19, 2021
• Study Start: March 31, 2022
• Primary Completion: April 15, 2023
• Study Completion: July 12, 2023
• Last Updated: May 16, 2024
• Results First Posted: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5); DE (8); CA (6); US (8); CZ (2)