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Status:

RECRUITING

Phase 2b Study to Investigate the Safety and Efficacy of TIN816 in Sepsis-associated Acute Kidney Injury (CLEAR-AKI)

Lead Sponsor:

Novartis Pharmaceuticals

Conditions:

Acute Kidney Injury Due to Sepsis

Eligibility:

All Genders

18-85 years

Phase:

PHASE2

Brief Summary

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...

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled, four-arm, parallel-group, dose-finding phase 2b study. The study will enroll hospitalized adult participants with a diagnosis of se...

Eligibility Criteria

Inclusion

  • Inclusion Criteria:
  • Signed informed consent must be obtained in accordance with local regulations.
  • ≥ 18 to ≤ 85 years of age
  • Admitted to ICU or intermediate care unit/ high dependency care unit (HDU)
  • Diagnosis of sepsis according to criteria defined by The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) based on:
  • Suspected or confirmed infection AND
  • Acute increase of SOFA score of 2 or more (excluding renal component). The baseline SOFA score should be assumed to be zero unless the participant is known to have pre-existing (acute or chronic) organ dysfunction before the onset of infection
  • Diagnosis of AKI Stage 1 or greater per the following criterion at randomization:
  • An absolute increase in serum or plasma creatinine by ≥ 0.3 mg/dL (≥ 26.5 µmol/L) within 48 hours or presumed to have occurred in the previous 48 hours as compared to the reference serum creatinine.
  • For participants with hospital-acquired AKI, a stable serum creatinine obtained in the hospital prior to AKI diagnosis should be used as the reference serum creatinine.
  • For participants presenting from community, the reference serum creatinine should be estimated using the following order of preference:
  • The most recent value within 3 months of the hospital admission. If not available:
  • The most recent value between 3 and 12 months prior to hospital admission. If not available:
  • At hospital admission
  • Exclusion criteria
  • Not expected to survive for 24 hours
  • Not expected to survive for 30 days due to medical conditions other than SA-AKI
  • History of CKD with a documented estimated GFR \<30 mL/min prior to admission to hospital
  • eGFR \<45mL/min at admission without any other reference serum eGFR within last 12-months
  • Receiving RRT or a decision has been made to initiate RRT within 24 hours after randomization
  • Weight is less than 40 kg or more than 125 kg.
  • Limitations to the use of mechanical ventilation, RRT or vasopressors/inotropes (N.B. limitations on Cardiopulmonary resuscitation (CPR)e.g., do-not-resuscitate orders are not an exclusion criterion unless associated with likely poor outcome in next 24 hours)
  • Sepsis diagnosis according to sepsis inclusion criteria for a period longer than 72 hours prior to ICU admission
  • AKI diagnosis according to AKI inclusion criteria over 48 hours after admission to ICU
  • Inability to administer study drug within 24 hours of diagnosis of AKI according to AKI inclusion criteria
  • Presence of AKI, in the Investigator's opinion, as suggested by clinical manifestation, e.g., prolonged oliguria or severe renal dysfunction on admission without a history of CKD, for a period longer than 24 hours prior to study drug administration
  • Evidence of recovery from AKI based on the investigator's clinical judgement prior to randomization
  • AKI is most likely attributable to other causes than sepsis, such as nephrotoxic drugs (Non-steroidal anti-inflammatory drugs (NSAIDs), contrast, aminoglycosides, etc.) or renal perfusion-related (acute abdominal aortic aneurysm, dissection, renal artery stenosis), urinary obstruction
  • Documented (biopsy proven) or suspected history of acute or sub-acute kidney diseases such as rapidly progressive glomerular nephritis (RPGN) and acute interstitial nephritis (AIN)
  • Patients who are post-nephrectomy
  • Patients with permanent incapacitation
  • Patients who are thrombocytopenic at screening (platelet count \<50,000 per microliter) who have active/uncontrolled bleeding or who present current or past conditions indicating high risk for bleeding in the opinion of the investigator (e.g. coagulopathies, previous history of major non-traumatic bleeding etc.)
  • Immunosuppressed patients
  • History of immunodeficiency diseases
  • Receiving immunosuppressant treatment or on chronic high doses (high-dose therapy exceeding 2 weeks of treatment) of steroids equivalent to prednisone/prednisolone 0.5 mg/kg/day, including solid organ transplant patients. Patients with septic shock treated with corticosteroids (as per the Surviving Sepsis Guidelines) can be included.
  • Patients with known or presumed latent or active TB based on clinical history or imaging e.g. patients on TB preventive therapy or close/household contacts of pulmonary TB patients
  • Known active hepatitis B or C infection (clinical diagnosis or positive infection serology), or advanced chronic liver disease, confirmed by a Child-Pugh score of 10-15 (Class C)
  • Acute pancreatitis with no established source of infection
  • Active hematological malignancy (previous hematological malignancies that are not actively treated are allowable)
  • Burns requiring ICU treatment
  • Sepsis attributed to confirmed COVID-19
  • Use of other investigational drugs within 5 half-lives of enrollment, within 30 days (e.g., small molecules) or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or longer if required by local regulations
  • History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes
  • Any medical conditions that could significantly increase risk of participants' safety by participating in this study according to investigator's judgement
  • Women with a positive pregnancy test, pregnancy or breast feeding
  • Women of childbearing potential, unless they are using highly effective methods of contraception for the entire duration of the trial.

Exclusion

    Key Trial Info

    Start Date :

    January 18 2024

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ESTIMATED

    End Date :

    April 21 2026

    Estimated Enrollment :

    320 Patients enrolled

    Trial Details

    Trial ID

    NCT05996835

    Start Date

    January 18 2024

    End Date

    April 21 2026

    Last Update

    December 23 2025

    Active Locations (122)

    Enter a location and click search to find clinical trials sorted by distance.

    Page 1 of 31 (122 locations)

    1

    University Of Alabama

    Birmingham, Alabama, United States, 35233

    2

    UC San Francisco Medical Center

    San Francisco, California, United States, 94143-0116

    3

    Stanford Healthcare

    Stanford, California, United States, 94305 5152

    4

    Emory Johns Creek Hospital

    Johns Creek, Georgia, United States, 30097