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Acute Kidney InjuryPhase 2AKITANCT05126303

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

A Phase 2 study testing RMC-035 in people with Acute Kidney Injury, run by Guard Therapeutics AB at 29 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 84 years
Conditions the study is for
Acute Kidney Injury
What is being tested?
RMC-035
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
177 participants
Where
29 sitesin 5 countries
Study dates
31 Mar 2022to 12 Jul 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 84 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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)
Show all 17Show fewer
  • 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
  • Received an investigational medicinal product within the last 90 days (or within 5 half-lives of the investigational drug, whichever is longer)
  • Subject has a known allergy to RMC-035 or one of its constituents, or has previously received RMC-035

Trial locations and contacts

29 sites in 5 countries.

29 sites in 5 countries

United States8 sites
  • University of Virginia (UVA) Health - University Hospital

    Charlottesville, Virginia, 22908

  • Baylor Scott and White Research Institute - Dallas

    Dallas, Texas, 75226

  • Duke University Hospital

    Durham, North Carolina, 27710

  • Indiana Ohio Heart

    Fort Wayne, Indiana, 48604

  • Bryan Heart

    Lincoln, Nebraska, 68506

  • University of Wisconsin

    Madison, Wisconsin, 53706

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

    Milwaukee, Wisconsin, 53215

  • Rochester Regional Health - Rochester General Hospital

    Rochester, New York, 14621

Other trials in United States

Germany8 sites
  • Herz- und Diabeteszentrum Nordrhein-Westfalen (NRW)

    Bad Oeynhausen

  • Universitätsklinikum Köln

    Cologne

  • Herzzentrum Dresden GmbH

    Dresden

  • Westdeutsches Herzzentrum Essen

    Essen

  • Universitätsklinikum Giessen und Marburg - Standort Giessen

    Giessen

  • Universitätsklinikum Halle (Saale)

    Halle

  • Deutsches Herzzentrum München

    München

  • Münster University Hospital

    Münster, DE-481 49

Other trials in Germany

Canada6 sites
  • Hamilton Health Sciences

    Hamilton

  • CHUM

    Montreal

  • MUHC - Royal Victoria Hospital

    Montreal

  • Institut Universitaire de Cardiologie et de Pneumologie de Québec

    Québec

  • St. John Regional Hospital

    Saint John

  • Saint Michael's Hospital

    Toronto

Other trials in Canada

Spain5 sites
  • Hospital Sant Pau

    Barcelona

  • Reina Sofia University Hospital

    Córdoba

  • Hospital de La Princesa

    Madrid

  • Hospital Universitario Central de Asturias

    Oviedo

  • Complejo Hospitalario Universitario de Santiago (CHUS)

    Santiago de Compostela

Other trials in Spain

Czechia2 sites
  • University Hospital Hradec Kralove

    Hradec Králové

  • University Hospital Motol - Charles University Prague

    Prague

Other trials in Czechia

About this study

Official title: A Phase 2, Randomized, Placebo-Controlled, Double-Blind, Adaptive, Parallel Group Clinical Study to Evaluate the Efficacy and Safety of RMC-035 in Subjects at High Risk for Acute Kidney Injury Following Open-Chest Cardiac Surgery

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.

Read the 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.

Being tested
RMC-035, Placebo
Medical subject headings
Acute Kidney Injury

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RMC-035Drug

    Also called ROSgard

    Concentrate for Solution for Infusion

  • PlaceboDrug

    Concentrate for Solution for Infusion

Study groups in NCT05126303
Study groupRoleWhat they receive
RMC-035ExperimentalRMC-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.
Receives: Drug: RMC-035
PlaceboPlacebo comparatorIdentical to RMC-035 arm except that the placebo contains no active ingredient.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 72 hours

Secondary outcomes (21)
  1. Area Under the Curve (AUC) of Serum Creatinine (SCr)

    Time-corrected area under the curve (AUC) of serum creatinine calculated as follows:

    The area under the SCr concentration versus time curve following drug administration were calculated using timepoints at Day 1 (12 hour), Day 2 (24 hour), Day 3 (48 hour) and Day 4 (72 hour). The individual log-transformed SCr values were determined, and the AUC (utilizing planned times) were calculated using the right Riemann sum: AUC = 0.5 x SCr(12h) + 0.5 x SCr(24h) + 1 x SCr(48h) + 1 x SCr(72h) The time-corrected AUC (log-scale) was then calculated as AUC/3

    Measured: 72 hours

  2. Duration of AKI

    Duration of AKI defined as the number of days meeting the definition of AKI (KDIGO definition) starting within 72 hours after first dose of IMP until resolution

    Measured: 90 days

  3. Change in SCr Values Over Time

    SCr at 12, 24, 48, and 72 hours, respectively, and at Day 7/discharge, Day 30 and Day 90

    Measured: 90 days

  4. Peak Cystatin C Value

    Change from baseline of peak cystatin C from baseline to Day 7

    Measured: 7 days

  5. AUC of Cystatin C

    Time-corrected AUC of cystatin C for Day 1 to Day 4 (72 hours after first dose of IMP) calculated as follows:

    The area under the cystatin C concentration versus time curve following drug administration were calculated using timepoints at Day 1 (12 hour), Day 2 (24 hour), Day 3 (48 hour) and Day 4 (72 hour). The individual log-transformed cystatin C values were determined, and the AUC (utilizing planned times) were calculated using the right Riemann sum: AUC = 0.5 x cystatin C(12h) + 0.5 x cystatin C(24h) + 1 x cystatin C(48h) + 1 x cystatin C(72h) The time-corrected AUC (log-scale) was then calculated as AUC/3

    Measured: 72 hours

  6. Number of Participants Requiring Renal Replacement Therapy (Dialysis)

    Renal replacement therapy (dialysis treatment) required by any participant for any reason

    Measured: 7 days

  7. Number of Days Without Need for Dialysis

    Number of days that participants were not requiring dialysis

    Measured: 90 days

  8. Major Adverse Kidney Event (MAKE) - SCr

    MAKE at Day 30 and Day 90, defined as death, any dialysis, or ≥25% reduction of eGFR compared to baseline.

    eGFR calculated based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using SCr.

    Measured: 90 days

  9. AKI Within 72 Hours Based on Cystatin C and UO

    AKI based on cystatin C and/or urine output (UO)

    Measured: 72 hours

  10. AKI Within 7 Days

    AKI based on SCr and/or UO criteria, or cystatin C and/or UO criteria

    Measured: 7 days

  11. Persistence of AKI

    AKI persistence, defined as an AKI (KDIGO definition) developing within 72 hours after first dose of IMP and with a duration of ≥72 hours

    Measured: 7 days

  12. Severity of AKI

    AKI severity stage 1, 2 or 3 per KDIGO criteria, with 1 being mildest stage and 3 being most severe stage.

    Reference: KDIGO (2012). "Clinical Practice Guideline for Acute Kidney Injury." JOURNAL OF THE INTERNATIONAL SOCIETY OF NEPHROLOGY 2(1).

    Measured: 7 days

  13. Change in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR)

    Post-baseline changes in UACR and UPCR at Day 4, Day 30, and Day 90

    Measured: 90 days

  14. Pharmacokinetics of RMC-035 (AUC)

    AUC(0-24) of RMC-035 concentrations in plasma (Day 3)

    Measured: 4 days

  15. Pharmacokinetics of RMC-035 (Cmax)

    Cmax of RMC-035 concentrations in plasma Day 3

    Measured: 7 days

  16. Presence of Anti-drug Antibodies (ADA)

    Presence of ADA at Day 1 (pre-surgery), Day 30, and Day 90; positive samples

    Measured: 90 days

  17. Characteristics of ADA (Cross-reactivity)

    Characteristics of ADA developed at Day 30 and Day 90 with regards cross-reactivity with endogenous alpha-1-microglobulin (A1M)

    Measured: 90 days

  18. Peak SCr Value

    Change from baseline of peak SCr from baseline to Day 7

    Measured: 7 days

  19. Major Adverse Kidney Event (MAKE) - Cystatin C

    MAKE at Day 30 and Day 90, defined as death, any dialysis, or ≥25% reduction of eGFR compared to baseline.

    eGFR calculated based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using Cystatin C.

    Measured: 90 days

  20. Major Adverse Kidney Event (MAKE) - SCr and Cystatin C

    MAKE at Day 30 and Day 90, defined as death, any dialysis, or ≥25% reduction of eGFR compared to baseline.

    eGFR calculated based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using SCr and Cystatin C.

    Measured: 90 days

  21. Change in Serum Cystatin C Values Over Time

    Cystatin C measurement in serum at 12, 24, 48, and 72 hours, respectively, and at Day 7/discharge, Day 30 and Day 90

    Measured: 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Nov 2021
  2. Study start31 Mar 2022
  3. Primary completion15 Apr 2023
  4. Study completion12 Jul 2023

Why it stopped: Enrollment discontinued following DMC recommendation based on futility with regards to primary endpoint

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, double-blind, adaptive, parallel group
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
177 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05126303
Sponsor's protocol ID
21-ROS-05
Acronym
AKITA
Status last verified
May 2024
First submitted
8 Nov 2021
Last updated
16 May 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39318788
  • 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.

    PubMed 37024249

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RMC-035 in people with Acute Kidney Injury, run by Guard Therapeutics AB at 29 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States, Germany, Canada, Spain, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Subjects Developing AKI, as Defined Per Kidney Disease Improving Global Outcomes (KDIGO) Criteria (time frame: 72 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05126303, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2024.

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