RMC-035 for Acute Kidney Injury

(POINTER Trial)

Recruiting at 39 trial locations

Overseen By Sara Thuresson

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Guard Therapeutics AB

Disqualifiers: Emergent surgeries, Cardiogenic shock, Sepsis, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 week

170 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug RMC-035 for treating acute kidney injury?

RMC-035, a modified version of alpha-1-microglobulin, has shown potential in preventing acute kidney injury in cardiac surgery patients due to its antioxidant and tissue-protective properties. It was found to be safe and well-tolerated in early clinical studies, suggesting it could help protect the kidneys during surgery. ^{1 2 3 4 5}

Is RMC-035 safe for humans?

RMC-035, also known as Recombinant Alpha-1-Microglobulin, was found to be safe and generally well tolerated in four phase 1 clinical studies. ^{1 2 3 5 6}

How is the drug RMC-035 different from other treatments for acute kidney injury?

RMC-035 is unique because it is a modified version of alpha-1-microglobulin, a natural protein with antioxidant and protective properties, designed to prevent kidney injury after cardiac surgery. Unlike other treatments, it specifically targets and protects kidney cells from damage during surgery. ^{1 3 4 5 7}

What is the purpose of this trial?

The goal of this clinical trial is to identify the optimal dose of RMC-035 for protection of long-term renal function in adult patients undergoing cardiac surgery who are at high risk of kidney injury. It will also learn about the safety of RMC-035. The main question it aims to answer is: * Does RMC-035 protect the function of kidneys after surgery? * Is RMC-035 safe? Researchers will compare RMC-035 in high dose, RMC-035 in low dose and placebo to see if * Kidney function better for participants treated with any of the RMC-035 doses? * What medical problems do participants have when receiving RMC-035? Participants will * Receive 3 doses of RMC-035 or placebo: at the beginning of surgery, end of surgery and 24h after surgery * Have extra checkups and tests during their hospital stay * Visit the clinic at two extra occasions at 60 days and 90 days after surgery for checkups and tests

Research Team

Michael Reusch, MD

Principal Investigator

Guard Therapeutics

Eligibility Criteria

This trial is for adult patients undergoing open-chest cardiac surgery who are at high risk of acute kidney injury. Participants will receive three doses of either RMC-035 or a placebo during and after their surgery, with additional checkups and tests during their hospital stay and follow-up visits at 60 and 90 days post-surgery.

Inclusion Criteria

Participant capable of providing written informed consent

Participant agrees to study restrictions such as not to take part in another interventional study, use contraception and not donate ova or sperm

My kidney function is at a safe level for treatment.

Exclusion Criteria

Any medical condition that makes the participant unsuitable

I am scheduled for an urgent surgery.

I am scheduled for heart surgery, including for blocked arteries, valve issues, or an aorta aneurysm.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 3 doses of RMC-035 or placebo: at the beginning of surgery, end of surgery, and 24h after surgery

1 week

In-hospital stay with multiple checkups and tests

Follow-up

Participants are monitored for safety and effectiveness after treatment, with clinic visits at 60 and 90 days post-surgery

90 days

2 visits (in-person) at 60 and 90 days

Long-term monitoring

Monitoring of renal function and safety outcomes, including eGFR and ADA presence

90 days

Treatment Details

Interventions

• RMC-035

Trial Overview The study is testing the effectiveness of two different doses of RMC-035 compared to a placebo in protecting long-term kidney function after cardiac surgery. It aims to determine the optimal dose for renal protection and assess the safety profile of RMC-035.

Participant Groups

Group I: RMC-035 low-dose Experimental Treatment 1 Intervention

RMC-035 30 mg

Group II: RMC-035 high-dose Experimental Treatment 1 Intervention

RMC-035 60 mg

Group III: Placebo Placebo Group 1 Intervention

Placebo (tris-buffer)

RMC-035 is already approved in United States, European Union, Canada for the following indications:

Approved in United States as RMC-035 for:

• None approved; Investigational New Drug (IND) clearance for clinical studies

Approved in European Union as RMC-035 for:

• None approved; under clinical investigation

Approved in Canada as RMC-035 for:

• None approved; under clinical investigation

Who Is Running the Clinical Trial?

Guard Therapeutics AB

Lead Sponsor

Trials

3

Recruited

350+

Findings from Research

In a study of 20 patients with severely impaired kidney function after extracorporeal circulation, those with higher preoperative levels of alpha 1-microglobulin (alpha 1-m I) were more likely to require postoperative hemodialysis, indicating a correlation between tubular damage and the need for dialysis.

Specifically, 6 out of 13 patients in the group with abnormal tubular and glomerular function (Group I) needed hemodialysis, while none in the group with normal function (Group III) did, suggesting that preoperative kidney damage can lead to prolonged or irreversible issues post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of highly damaged renal function following extracorporeal circulation--usefulness of alpha 1-microglobulin index]. Narisawa, T., Murakami, A., Aiba, M., et al.[2019]

In a study of 1,464 adults undergoing cardiac surgery, higher preoperative levels of urine alpha-1-microglobulin (Uα1m) were linked to an increased risk of acute kidney injury (AKI), chronic kidney disease (CKD) progression, and all-cause mortality, indicating its potential as a predictive biomarker.

Postoperative Uα1m levels did not show any significant association with AKI, CKD incidence or progression, cardiovascular events, or mortality, suggesting that only preoperative measurements are valuable for assessing risk in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urine Alpha-1-Microglobulin Levels and Acute Kidney Injury, Mortality, and Cardiovascular Events following Cardiac Surgery. Amatruda, JG., Estrella, MM., Garg, AX., et al.[2022]

In a phase 1b clinical study involving 12 cardiac surgery patients, RMC-035, a recombinant variant of alpha-1-microglobulin, was found to be well tolerated with no serious adverse events related to the drug, indicating its safety for use in this population.

Treatment with RMC-035 resulted in reduced levels of established urine biomarkers for acute kidney injury, suggesting it may effectively protect against kidney cell injury during cardiac surgery and warrants further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant Alpha-1-Microglobulin (RMC-035) to Prevent Acute Kidney Injury in Cardiac Surgery Patients: Phase 1b Evaluation of Safety and Pharmacokinetics. Weiss, R., Meersch, M., Wempe, C., et al.[2023]

In a study of 77 bone marrow transplant recipients, elevated levels of alpha-1 microglobulin (alpha 1m) and beta-2 microglobulin (beta 2m) were significantly associated with renal impairment, particularly during nephrotoxic drug treatment, indicating their potential as biomarkers for kidney function.

Alpha 1m levels were less affected by infections and acute graft-versus-host disease compared to beta 2m, suggesting that alpha 1m could serve as a complementary measure alongside serum creatinine for monitoring renal function post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum levels of alpha-1 microglobulin and beta-2 microglobulin in bone marrow transplant recipients treated with cyclosporin A. Duraj, FF., Bäckman, L., Dati, F., et al.[2019]

RMC-035, a modified variant of the protein alpha-1-microglobulin, is being tested in a phase 2 clinical trial involving approximately 268 cardiac surgery patients to see if it can reduce the incidence of acute kidney injury (AKI) after surgery.

The study is designed to evaluate both the safety and efficacy of RMC-035, with an independent monitoring committee overseeing the trial, ensuring that the treatment is well-tolerated and potentially beneficial for improving kidney function post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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). Mazer, CD., Siadati-Fini, N., Boehm, J., et al.[2023]

A BALB/c mouse was successfully immunized with a mixture of alpha 1-microglobulin from multiple species, leading to the generation of nine unique monoclonal antibodies that specifically target this glycoprotein.

These monoclonal antibodies demonstrated efficacy in various assays, including solid-phase radioimmunoassays and Western blots, indicating their potential as valuable tools for further research on alpha 1-microglobulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross-reacting monoclonal anti-alpha 1-microglobulin antibodies produced by multi-species immunization and using protein G for the screening assay. Nilson, B., Akerström, B., Lögdberg, L.[2019]

Urine alpha1-microglobulin (α1m) levels can serve as an early predictor for the development of sepsis-associated acute kidney injury (SAAKI) in critically ill patients, with a sensitivity of 87.5% and specificity of 62.07%.

In a study of 286 ICU patients, those with elevated urine α1m levels 24 hours before SAAKI onset showed a significant correlation, and combining α1m levels with serum creatinine and APACHE II scores improved prediction accuracy to an AUC of 0.944.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha1-microglobulin as an early biomarker of sepsis-associated acute kidney injury: a prospective cohort study. Terzi, I., Papaioannou, V., Papanas, N., et al.[2020]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Evaluation of highly damaged renal function following extracorporeal circulation--usefulness of alpha 1-microglobulin index]. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Urine Alpha-1-Microglobulin Levels and Acute Kidney Injury, Mortality, and Cardiovascular Events following Cardiac Surgery. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Recombinant Alpha-1-Microglobulin (RMC-035) to Prevent Acute Kidney Injury in Cardiac Surgery Patients: Phase 1b Evaluation of Safety and Pharmacokinetics. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Serum levels of alpha-1 microglobulin and beta-2 microglobulin in bone marrow transplant recipients treated with cyclosporin A. [2019]

5. England pubmed.ncbi.nlm.nih.gov

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). [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Cross-reacting monoclonal anti-alpha 1-microglobulin antibodies produced by multi-species immunization and using protein G for the screening assay. [2019]

7. Greece pubmed.ncbi.nlm.nih.gov

Alpha1-microglobulin as an early biomarker of sepsis-associated acute kidney injury: a prospective cohort study. [2020]