RMC-035 for Acute Kidney Injury

(POINTER Trial)

No longer recruiting at 44 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a new medicine, RMC-035 (Recombinant Alpha-1-Microglobulin), in protecting kidneys after heart surgery. The study compares high and low doses of RMC-035 to a placebo (a harmless substance with no active ingredient) to determine if either dose improves kidney function. Individuals undergoing specific types of heart surgery with risk factors for kidney injury may be suitable candidates. Participants will receive the treatment during and after surgery, with additional checkups in the hospital and at follow-up visits. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that RMC-035 is likely to be safe for humans?

Research has shown that RMC-035 has been tested for safety in patients undergoing heart surgery. Results indicated that RMC-035 was generally well-tolerated, with most patients experiencing no serious side effects. However, some studies noted it did not significantly reduce kidney injury after surgery, suggesting its effects might vary.

These studies carefully monitored the safety of RMC-035. While specific side effects were not listed, researchers typically check for major health issues. As this trial is in an early stage and RMC-035 is not yet approved for other uses, its safety continues to be studied.

Participants in this trial will receive either a low or high dose of RMC-035 or a placebo (a substance with no active drug). This setup allows for a comparison of the effects and safety of different doses. The study will monitor any health problems that occur with RMC-035 to ensure its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for acute kidney injury, which often involve supportive care such as managing fluid balance and avoiding nephrotoxic drugs, RMC-035 offers a novel approach. Researchers are excited about RMC-035 because it targets the underlying cellular mechanisms directly involved in kidney injury. This treatment works by modulating oxidative stress pathways, potentially reducing damage at a molecular level. By addressing these fundamental processes, RMC-035 could not only protect kidney function more effectively but also speed up recovery times compared to existing options.

What evidence suggests that RMC-035 might be an effective treatment for acute kidney injury?

This trial will compare different dosages of RMC-035 with a placebo to evaluate its effectiveness for acute kidney injury. Research has shown mixed results regarding RMC-035's ability to aid kidney function after surgery. One study found that RMC-035 did not significantly reduce the risk of sudden kidney problems within 72 hours after heart surgery. However, other studies have demonstrated positive effects on kidney function post-surgery. These studies suggest that RMC-035 might be beneficial in situations involving stress on the body and reduced blood flow to the kidneys. While there is some promise, results have varied, and further research is needed to confirm its efficacy. ^{1 3 5 6 7}

Who Is on the Research Team?

Michael Reusch, MD

Principal Investigator

Guard Therapeutics

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

Citations

1. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00409-7/fulltext

Efficacy and safety of therapeutic alpha-1-microglobulin ... In this proof-of-concept study, RMC-035 did not reduce AKI 72 h after cardiac surgery. Evaluations may have been confounded by a drug-induced ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41014235/

Recombinant alpha-1 microglobulin to improve outcomes ... Although a Phase 2 trial in cardiac surgery patients did not meet its primary endpoint of reducing the rate of AKI within 72 hours after surgery ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05126303

Efficacy and Safety of RMC-035 in Subjects at High Risk for ... 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 ...

4. guardtherapeutics.com guardtherapeutics.com/en/press-releases/guard-therapeutics-announces-new-positive-efficacy-results-from-secondary-analyses-of-the-phase-2a-akita-study

Press release The previously reported primary results demonstrated a robust improvement in kidney function following open-heart surgery. The new analyses ...

5. academic.oup.com academic.oup.com/ndt/advance-article-abstract/doi/10.1093/ndt/gfaf194/8266817

Recombinant alpha-1 microglobulin to improve outcomes in ... Collectively, these studies seek to answer whether RMC-035 may improve kidney outcomes in settings characterized by oxidative and ischemia- ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10166741/

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

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39318788/

Efficacy and safety of therapeutic alpha-1-microglobulin ... The AKITA study evaluated the efficacy and safety of RMC-035, a novel analogue of alpha-1-microglobulin, for reducing cardiac surgery-associated kidney injury.