TIN816 for Acute Kidney Injury
(CLEAR-AKI Trial)
Recruiting in Palo Alto (17 mi)
+108 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Novartis Pharmaceuticals
Must not be taking: NSAIDs, Immunosuppressants, Aminoglycosides, others
Disqualifiers: CKD, Immunosuppression, Active TB, others
Prior Safety Data
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?
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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Trial 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 (Other)
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
Research Locations NearbySelect from list below to view details:
Novartis Investigative SiteVancouver, Canada
Novartis Investigative SiteSainte Foy, Canada
UC San Francisco Medical CenterSan Francisco, CA
Montefiore Medical Center Montefiore Medical CenterBronx, NY
More Trial Locations
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Who Is Running the Clinical Trial?
Novartis PharmaceuticalsLead Sponsor
References
Double-Negative T Cells Attenuate Cisplatin-Induced Acute Kidney Injury via Upregulating IL-10/AT2R Axis. [2023]Our previous research showed that TCR+CD4-CD8-double-negative (DN) T cells protect renal epithelial cells from cisplatin-induced acute kidney injury (AKI). Therefore, this study is aimed at investigating the mechanism underlying the effect of DN T cells against Cis-induced AKI.
Increased urinary excretion of albumin, hemopexin, transferrin and VDBP correlates with chronic sensitization to gentamicin nephrotoxicity in rats. [2015]Drug nephrotoxicity is a serious health and economic problem worldwide. Rats can be acutely sensitized to acute kidney injury (AKI) by subnephrotoxic treatments with potentially nephrotoxic drugs. Acquired sensitization to AKI poses a silent risk impossible to diagnose pre-emptively with the technology available at the clinical level. Herein, we hypothesized whether a chronic, subnephrotoxic insult to the kidneys might result in chronically acquired sensitization to AKI, and whether chronic sensitization might be detected through specific urinary markers. To this end, rats were treated with a subtoxic dosage of the experimental nephrotoxin uranyl nitrate (UN) in the drinking water for 21 weeks, or plain water (as control), and then with low-dose gentamicin for 7 days. Renal function and renal tissue damage were evaluated through the experiment. The mild renal damage caused by gentamicin was markedly magnified in rats having received UN chronically, which was evident both at the functional and histological level. Four proteins, namely albumin, hemopexin, transferrin and vitamin D binding protein were increased in the urine in temporal association with the appearance of chronic predisposition. Although further studies are necessary, our results suggest that these proteins might be potentially used as markers of hidden, chronic predisposition to gentamicin nephrotoxicity, in order to appropriately and pre-emptively stratify and handle individuals according to their specific risk in the long term, and to conveniently optimize their life conditions or additional clinical procedures or treatments that might trigger the disease. This might reduce AKI incidence and severity and the associated costs.
Mouse models and methods for studying human disease, acute kidney injury (AKI). [2014]Acute kidney injury (AKI) is serious complication in hospitalized patients with high level of mortality. There is not much progress made for the past 50 years in reducing the mortality rate despite advances in understanding disease pathology. Using variety of animal models of acute kidney injury, scientist studies the pathogenic mechanism of AKI and to test therapeutic drugs, which may reduce renal injury. Among them, renal pedicle clamping and cisplatin induced nephrotoxicity in mice are most prominently used, mainly due to the availability of gene knockouts to study specific gene functions, inexpensive and availability of the inbred strain with less genetic variability. However, ischemic mouse model is highly variable and require excellent surgical skills to reduce variation in the observation. In this chapter, we describe a detailed protocol of the mouse model of bilateral renal ischemia-reperfusion and cisplatin induced nephrotoxicity. We also discuss the protocol for the isolation and analysis of infiltrated inflammatory cell into the kidney by flow cytometry. Information provided in this chapter will help scientist who wants to start research on AKI and want to establish the mouse model for ischemic and toxic kidney injury.
Early diagnostic biomarkers for acute kidney injury using cisplatin-induced nephrotoxicity in rat model. [2023]Chronic kidney diseases (CKD) caused by acute kidney injury (AKI) results rapid and reversible loss in renal function. A real-time, highly accurate, and sensitive acute kidney injury biomarker is urgently required in order to keep these patients alive and prevent end stage renal disease and related complications that include hypertension, fluid and electrolyte retention, metabolic acidosis, anemia, stroke etc. This study was designed to develop a specific and sensitive model for the early identification of renal damage in male albino rats. Using a single intraperitoneal dose of cisplatin (10 mg/kg body weight) to the rats, the various duration-dependent nephrotoxic activities were compared using multiple physiological, biochemical, genomic, and histopathological markers. We looked into when renal dysfunction would start occurring after receiving a single high dose of cisplatin while blood urea nitrogen (BUN) and serum creatinine (sCr) remained normal. Following a single cisplatin injection, various measurements were taken in plasma, urine, and/or kidney tissues of rats euthanized on days 1, 2, 3, 5, and 7. When the urine kidney injury molecule (KIM-1), interleukine 18 (IL-18), nephrin, neutrophil gelatinase-associated lipocalin (NGAL) and serum cystatin C (Cys C) levels are greatly raised on day 3 after cisplatin treatment, BUN and sCr levels remain normal. Nephrotoxicity of cisplatin is also indicated by the upregulated mRNA expression of KIM-1, IL-18, Cys C, and NGAL and downregulated expression of nephrin in kidney tissue at very initial stage. Protein expression of KIM-1, IL-18 and NGAL level of kidney tissues was upregulated indicated confirmatory results done by western blot. Utilising an array of kidney impairment indicators has emerged as an earlier, more effective, and more reliable technique to diagnose AKI when compared to the most sophisticated signs now available.
Double-Negative αβ T Cells Are Early Responders to AKI and Are Found in Human Kidney. [2020]Ischemia-reperfusion injury (IRI) is a major cause of AKI, and previous studies established important roles for conventional CD4(+) T cells, natural killer T cells, and CD4(+)CD25(+)FoxP3(+) Tregs in AKI pathogenesis. We recently identified CD4(-)CD8(-) (double-negative; DN) T cells as an important subset of αβ T cell receptor-positive cells residing in mouse kidney. However, little is known about the pathophysiologic functions of kidney DN T cells. In this study, we phenotypically and functionally characterized murine kidney DN T cells in the steady state and in response to IRI. Unlike CD4(+) and CD8(+) T cells, DN T cells in the steady state expressed high levels of CD69, CD28, and CD40L; differentially expressed IL-27 and IL-10 anti-inflammatory cytokines; spontaneously proliferated at a very high rate; and suppressed in vitro proliferation of activated CD4(+) T cells. Within the first 3-24 hours after IRI, kidney DN T cells expanded significantly and upregulated expression of IL-10. In adoptive transfer experiments, DN T cells significantly protected recipients from AKI by an IL-10-dependent mechanism. DN T cells also made up a large fraction of the T cell compartment in human kidneys. Our results indicate that DN T cells are an important subset of the resident αβ(+) T cell population in the mammalian kidney and are early responders to AKI that have anti-inflammatory properties.