TIN816 for Acute Kidney Injury

Recruiting at 45 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must not be taking: Investigational drugs

Disqualifiers: Renal therapy, Bleeding risk, Sepsis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 days

98 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized, multi-centric, placebo-controlled, participant and investigator-blinded study to evaluate the safety, tolerability and efficacy of TIN816 in adult patients at risk for acute kidney injury following cardiac surgery.

Do I need to stop my current medications for the TIN816 trial?

The trial protocol does not specify if you need to stop taking your current medications. However, your pulse rate should be stable with or without medication, and you cannot use other investigational drugs close to the time of enrollment.

How is the drug TIN816 different from other treatments for acute kidney injury?

TIN816 may be unique in its approach to treating acute kidney injury by potentially involving double-negative T cells, which have been shown to protect kidney cells from damage and have anti-inflammatory properties, unlike traditional treatments that do not target these specific immune cells. ^{1 2 3 4 5}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticasl

Eligibility Criteria

Adults over 45 years old at risk of kidney injury after non-emergency heart surgery can join. They must be able to understand the study, weigh between 50-150 kg with a BMI under 40, and have stable vital signs. They cannot have had a recent significant increase in creatinine levels.

Inclusion Criteria

No known increase in SCr of ≥25% at screening visit compared to a previous value not older than 6 weeks as documented by a local laboratory using standard assay methodology.

I am scheduled for a major heart or lung surgery that will use a heart-lung machine for over an hour.

Signed informed consent must be obtained prior to participation in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive TIN816 or placebo following cardiac surgery

6 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Treatment Details

Interventions

• Placebo
• TIN816

Trial Overview The trial is testing TIN816 against a placebo to see if it's safe and effective in preventing kidney damage following heart surgery. Participants are randomly assigned to either the drug or placebo without knowing which one they receive.

Participant Groups

Group I: TIN816 Experimental Treatment 1 Intervention

TIN816

Group II: Placebo Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

DN T cells help protect renal epithelial cells (HK-2) from cisplatin-induced acute kidney injury (AKI) by enhancing the expression of IL-10, which in turn activates the angiotensin AT2 receptor (AT2R).

The protective effects of DN T cells can be reversed by blocking IL-10 or AT2R, indicating that the IL-10/AT2R pathway is crucial for their protective mechanism against nephrotoxicity caused by cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-Negative T Cells Attenuate Cisplatin-Induced Acute Kidney Injury via Upregulating IL-10/AT2R Axis. Gong, J., Wu, J., Zhang, M., et al.[2023]

Chronic exposure to a subtoxic dose of uranyl nitrate in rats led to increased sensitivity to acute kidney injury (AKI) when subsequently treated with gentamicin, indicating that prior mild kidney damage can worsen the effects of nephrotoxic drugs.

Four urinary proteins (albumin, hemopexin, transferrin, and vitamin D binding protein) were identified as potential markers for chronic predisposition to nephrotoxicity, which could help in early detection and risk stratification for individuals at risk of AKI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased urinary excretion of albumin, hemopexin, transferrin and VDBP correlates with chronic sensitization to gentamicin nephrotoxicity in rats. Vicente-Vicente, L., Ferreira, L., González-Buitrago, JM., et al.[2015]

Acute kidney injury (AKI) remains a significant challenge in hospitalized patients, with high mortality rates and little progress in reducing these rates over the past 50 years, despite advances in understanding its pathology.

The chapter provides detailed protocols for using mouse models of AKI, specifically bilateral renal ischemia-reperfusion and cisplatin-induced nephrotoxicity, which are essential for studying the mechanisms of AKI and testing potential therapeutic drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mouse models and methods for studying human disease, acute kidney injury (AKI). Ramesh, G., Ranganathan, P.[2014]

This study developed a sensitive model for early detection of acute kidney injury (AKI) in male albino rats using a single dose of cisplatin, revealing that kidney injury markers like KIM-1 and IL-18 significantly increased by day 3, even when traditional markers like blood urea nitrogen (BUN) and serum creatinine (sCr) remained normal.

The research demonstrated that a combination of physiological, biochemical, genomic, and histopathological markers can provide a more reliable and earlier diagnosis of AKI compared to current methods, highlighting the importance of these biomarkers in preventing chronic kidney disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early diagnostic biomarkers for acute kidney injury using cisplatin-induced nephrotoxicity in rat model. Jana, S., Mitra, P., Dutta, A., et al.[2023]

In a study of murine kidney cells, CD4(-)CD8(-) double-negative T cells were identified as a significant subset that responds to ischemia-reperfusion injury (IRI) and exhibits anti-inflammatory properties, suggesting their potential role in protecting against acute kidney injury (AKI).

These DN T cells not only proliferate rapidly and produce anti-inflammatory cytokines like IL-10 but also significantly reduce AKI severity in recipient mice through an IL-10-dependent mechanism, highlighting their importance in kidney health and response to injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-Negative αβ T Cells Are Early Responders to AKI and Are Found in Human Kidney. Martina, MN., Noel, S., Saxena, A., et al.[2020]

References

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

Double-Negative T Cells Attenuate Cisplatin-Induced Acute Kidney Injury via Upregulating IL-10/AT2R Axis. [2023]

2. Ireland pubmed.ncbi.nlm.nih.gov

Increased urinary excretion of albumin, hemopexin, transferrin and VDBP correlates with chronic sensitization to gentamicin nephrotoxicity in rats. [2015]

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

Mouse models and methods for studying human disease, acute kidney injury (AKI). [2014]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Early diagnostic biomarkers for acute kidney injury using cisplatin-induced nephrotoxicity in rat model. [2023]

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

Double-Negative αβ T Cells Are Early Responders to AKI and Are Found in Human Kidney. [2020]