TIN816 for Acute Kidney Injury

(CLEAR-AKI Trial)

Recruiting at 136 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must not be taking: NSAIDs, Immunosuppressants, Aminoglycosides, others

Disqualifiers: CKD, Immunosuppression, Active TB, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

320 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a new treatment called TIN816 for individuals with sepsis-associated acute kidney injury (SA-AKI). Researchers aim to determine how different doses of TIN816 impact this condition and assess its safety and efficacy. Participants will receive one of three doses of TIN816 or a placebo, which has no treatment effect. This trial suits those in the ICU with sepsis who have experienced a sudden decline in kidney function. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TIN816 has been tested for safety in people with sepsis-related kidney problems. In earlier studies, TIN816 was generally well-tolerated. Researchers examined the drug's effects and how it worked in the body, finding that it caused few serious side effects.

Most participants in these studies did not experience severe adverse reactions. Any side effects that occurred were uncommon and not serious. This suggests that TIN816 is relatively safe, although further research is needed to confirm these findings.

This information comes from earlier research, and ongoing studies will provide more insights into the safety of TIN816. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute kidney injury?

Researchers are excited about TIN816 for acute kidney injury because it offers a potentially faster-acting solution compared to current options, which often include supportive care like dialysis and medications to manage symptoms. Unlike these treatments, TIN816 is administered as a single intravenous dose, which could simplify treatment logistics and improve patient compliance. Furthermore, the unique formulation of TIN816 might target kidney injury directly, potentially leading to quicker recovery times for patients.

What evidence suggests that TIN816 might be an effective treatment for acute kidney injury?

Research has shown that TIN816 could help treat kidney problems caused by sepsis. In earlier studies, patients who received TIN816 demonstrated better kidney function than those who did not, suggesting that TIN816 might speed up kidney healing in these cases. In this trial, participants will receive TIN816 as a one-time dose through an IV, with varying doses tested to determine the most effective amount. Early results indicate it is safe and could be beneficial, offering hope for people with this condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

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 currently in an ICU or a high dependency care unit.

A relative increase of at least 0.3 mg/dL (26.5 µmol/L) in serum or plasma creatinine levels within the preceding 48 hours, as compared to a reference value for same.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• TIN816

Trial Overview The 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.

How Is the Trial Designed?

Group I: TIN816 Dose C Experimental Treatment 1 Intervention

Administered as a one time intravenous dose

Group II: TIN816 Dose B Experimental Treatment 1 Intervention

Administered as a one time intravenous dose

Group III: TIN816 Dose A Experimental Treatment 1 Intervention

Administered as a one time intravenous dose

Group IV: Placebo Placebo Group 1 Intervention

0.9% sterile saline administered as a one time intravenous dose

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05996835

NCT05996835 | Phase 2b Study to Investigate the Safety ... Phase 2b Study to Investigate the Safety and Efficacy of TIN816 in Sepsis-associated Acute Kidney Injury (CLEAR-AKI) (CLEAR-AKI). ClinicalTrials.gov ID ...

2. novartis.com novartis.com/clinicaltrials/study/nct05996835

Phase 2b Study to Investigate the Safety and Efficacy ... 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 TIN ...

3. medcommshydhosting.com medcommshydhosting.com/CRM/Renal//ASN/presentations/2024/posters/ASN2024_A_multicenter_randomized_Poster.pdf

A multicenter, randomized, double-blind, placebo initial efficacy and safety of multiple dose levels of TIN816 in the treatment of SA-AKI. (NCT05996835). Scan to obtain: • Poster https://www.

4. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/acute-kidney-injury

UCSF Acute Kidney Injury Clinical Trials for 2025 TIN816 in Sepsis-associated Acute Kidney Injury (CLEAR-AKI) ... The purpose of this Ph2b study is to characterize the dose-response relationship ...

5. medcommshydhosting.com medcommshydhosting.com/CRM/Renal/ERA/presentations/2025/communication/ERA2025_Pharmacokinetics-Pharmacodynamics_FreeCommunication.pdf

Pharmacokinetics, Pharmacodynamics, and Safety of TIN816 ... Safety of TIN816 in Patients With Sepsis-Associated. Acute Kidney Injury: Results From a Randomized. Phase 2a Study. Julien Demiselle1,2, Nicolas De Schryver3 ...

6. academic.oup.com academic.oup.com/ndt/article/doi/10.1093/ndt/gfaf116.127/8294951

#1152 Pharmacokinetics, pharmacodynamics and safety of ... #1152 Pharmacokinetics, pharmacodynamics and safety of TIN816 in patients with sepsis-associated acute kidney injury: results from a randomized ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05507437

Pharmacokinetics and Safety of TIN816 in Patients With ... ... Safety and Tolerability of TIN816 in Patients With Sepsis-associated Acute Kidney Injury. Conditions. Acute Kidney Injury Due to Sepsis. Acute Kidney Injury ...