320 Participants Needed

TIN816 for Acute Kidney Injury

(CLEAR-AKI Trial)

Recruiting at 108 trial locations
NP
Overseen ByNovartis Pharmaceuticals
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

The purpose of this Ph2b study is to characterize the dose-response relationship and to evaluate the safety and efficacy of three different single doses of TIN816 in hospitalized adult participants in an intensive care setting with a diagnosis of sepsis-associated acute kidney injury (SA-AKI).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressant treatments or certain nephrotoxic drugs, you might not be eligible to participate. It's best to discuss your specific medications with the trial team.

What makes the drug TIN816 unique for treating 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.12345

Research Team

NP

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for adults aged 18-85 in intensive care with sepsis-associated acute kidney injury (SA-AKI). Participants must have a suspected or confirmed infection, an increase in SOFA score by 2 points excluding the renal component, and a significant rise in creatinine levels. They need to provide informed consent before joining.

Inclusion Criteria

My kidney function was stable before my recent AKI diagnosis.
I am between 18 and 85 years old.
I am currently in an ICU or a high dependency care unit.
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Timeline

Screening

Participants are screened for eligibility to participate in the trial

24-48 hours
1 visit (in-person)

Treatment

Participants receive a one-time intravenous infusion of TIN816 or placebo

1 day
1 visit (in-person)

Post-treatment

Participants are monitored for safety and efficacy assessments

90 days
Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • TIN816
Trial OverviewThe study tests three single doses of TIN816 against a placebo to see which is safer and more effective for SA-AKI patients. It's given as lyophilisate powder, aiming to understand how different amounts affect recovery from kidney injury due to sepsis.
Participant Groups
4Treatment groups
Experimental Treatment
Placebo Group
Group I: TIN816 Dose CExperimental Treatment1 Intervention
Administered as a one time intravenous dose
Group II: TIN816 Dose BExperimental Treatment1 Intervention
Administered as a one time intravenous dose
Group III: TIN816 Dose AExperimental Treatment1 Intervention
Administered as a one time intravenous dose
Group IV: PlaceboPlacebo Group1 Intervention
0.9% sterile saline administered as a one time intravenous dose

Find a Clinic Near You

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 profile image

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye profile image

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

References

Double-Negative T Cells Attenuate Cisplatin-Induced Acute Kidney Injury via Upregulating IL-10/AT2R Axis. [2023]
Increased urinary excretion of albumin, hemopexin, transferrin and VDBP correlates with chronic sensitization to gentamicin nephrotoxicity in rats. [2015]
Mouse models and methods for studying human disease, acute kidney injury (AKI). [2014]
Early diagnostic biomarkers for acute kidney injury using cisplatin-induced nephrotoxicity in rat model. [2023]
Double-Negative αβ T Cells Are Early Responders to AKI and Are Found in Human Kidney. [2020]