Pharmacokinetics and Safety of TIN816 in Patients With Sepsis-associated Acute Kidney Injury

NCT05507437 | Completed Phase 2 Results

• 2 other identifiers: CTIN816B122012022-000887-23
• Study Type: interventional
• Target: 20
• Locations: 5 countries
• Sites: 7

Brief Summary

The purpose of this study was to characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile and to evaluate the safety and tolerability of TIN816 in hospitalized adult participants in an intensive care setting with a diagnosis of sepsis-associated acute kidney injury (SA-AKI).

Conditions

Acute Kidney Injury Due to Sepsis

Keywords

Sepsis; acute kidney injury; intensive care; therapy

Outcome Measures

Primary Outcomes (7)

• Maximum Serum Concentration (Cmax) of TIN816

  Cmax is defined as the maximum (peak) observed concentration following a dose. TIN816 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). TIN816 concentrations were determined by a validated ligand binding assay with a lower limit of quantification (LLOQ) of 10 ng/mL.

  Day 1 (Pre-dose and 2 hours), Day 2, Day 3, Day 5, Day 8, Day 14, Day 30, Day 60 and Day 90

• Area Under Serum Concentration-time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of TIN816

  AUClast is the area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (tlast) of TIN816. TIN816 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). TIN816 concentrations were determined by a validated ligand binding assay with a lower limit of quantification (LLOQ) of 10 ng/mL.

  Day 1 (Pre-dose and 2 hours), Day 2, Day 3, Day 5, Day 8, Day 14, Day 30, Day 60 and Day 90

• Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-inf]) of TIN816

  The AUC from time zero to infinity (mass x time x volume-1). TIN816 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). TIN816 concentrations were determined by a validated ligand binding assay with a lower limit of quantification (LLOQ) of 10 ng/mL.

  Day 1 (Pre-dose and 2 hours), Day 2, Day 3, Day 5, Day 8, Day 14, Day 30, Day 60 and Day 90

• Time to Reach Maximum Serum Concentration (Tmax) of TIN816

  Tmax is the time to reach maximum (peak) drug concentration after single-dose administration (time). TIN816 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). TIN816 concentrations were determined by a validated ligand binding assay with a lower limit of quantification (LLOQ) of 10 ng/mL.

  Day 1 (Pre-dose and 2 hours), Day 2, Day 3, Day 5, Day 8, Day 14, Day 30, Day 60 and Day 90

• Terminal Elimination Half-life (T1/2) of TIN816

  T1/2 is the elimination half-life associated with the terminal slope. TIN816 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). TIN816 concentrations were determined by a validated ligand binding assay with a lower limit of quantification (LLOQ) of 10 ng/mL.

  Day 1 (Pre-dose and 2 hours), Day 2, Day 3, Day 5, Day 8, Day 14, Day 30, Day 60 and Day 90

• Total Body Clearance (CL) of TIN816

  CL is the total body clearance of TIN816 from the serum following intravenous administration (volume x time-1). TIN816 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). TIN816 concentrations were determined by a validated ligand binding assay with a lower limit of quantification (LLOQ) of 10 ng/mL.

  Day 1 (Pre-dose and 2 hours), Day 2, Day 3, Day 5, Day 8, Day 14, Day 30, Day 60 and Day 90

• The Apparent Volume of Distribution (Vz) of TIN816

  Vz is the apparent volume of distribution during terminal phase following intravenous administration. TIN816 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). TIN816 concentrations were determined by a validated ligand binding assay with a lower limit of quantification (LLOQ) of 10 ng/mL.

  Day 1 (Pre-dose and 2 hours), Day 2, Day 3, Day 5, Day 8, Day 14, Day 30, Day 60 and Day 90

Secondary Outcomes (1)

• Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 90 days.

Study Arms (2)

TIN816

EXPERIMENTAL

Administered as an intravenous dose

Biological: TIN816 70 mg lyophilisate powder

Placebo

PLACEBO COMPARATOR

0.9% sterile sodium chloride solution administered as an intravenous dose

Other: Placebo

Interventions

TIN816 70 mg lyophilisate powder BIOLOGICAL

Recombinant human CD39 enzyme

TIN816

Placebo OTHER

0.9% sterile sodium chloride solution

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study.
• ≥ 18 and ≤ 85 years of age.
• Admitted to ICU or intermediate/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 SOFA score of 2 or more (excluding renal component)
• Diagnosis of AKI Stage 1 or greater per the following criterion at randomization :
• An absolute increase in serum or plasma creatinine (CR) 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 creatinine baseline.
• For hospital-acquired AKI, a stable serum creatinine obtained in the hospital prior to AKI should be used as reference baseline, otherwise, baseline serum creatinine in the following order of preference:
• Median value within 3 months of the hospital admission. If not available:
• Median value between 3 and 6 months prior to hospital admission. If not available:
• At hospital admission.

You may not qualify if:

• 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 \<45 ml/min prior to development of AKI.
• Receiving RRT or a decision has been made to initiate RRT within 24 hours of admission.
• Weight is less than 40 kg or more than 125 kg .
• Has life support limitations (eg, do not resuscitate, do not dialyze, do not intubate).
• Presence of AKI for a period longer than 48 hours prior to study drug administration as suggested by clinical manifestations, e.g., prolonged oliguria or severe renal dysfunction (eg, serum creatinine \> 4 mg/dL) on admission without a history of CKD.
• Evidence of recovery from AKI based on the investigator's clinical judgement prior to randomization.
• AKI is most likely attributable to causes other than sepsis such as nephrotoxic drugs (Non-steroidal anti-inflammatory drugs (NSAIDs), contrast, aminoglycosides), other medical conditions (e.g. heart failure, liver failure, acute abdominal aortic aneurysm, dissection, renal artery stenosis) or 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 who are on dual antiplatelet therapy.
• Patients who are thrombocytopenic at screening (Platelet count \<100,000 microliter) or other high risk for bleeding in the opinion of the investigator.
• Immunosuppressed patients:
• History of immunodeficiency diseases or known HIV test positive. Is receiving immunosuppressant treatment or is 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 hydrocortisone (e.g., 3 × 100 mg) can be included.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

Novartis Investigative Site

Genk, 3600, Belgium

Location

Novartis Investigative Site

Ottignies, 1340, Belgium

Location

Novartis Investigative Site

Strasbourg, 67091, France

Location

Novartis Investigative Site

Toulouse, 31054, France

Location

Novartis Investigative Site

Kiel, 24105, Germany

Location

Novartis Investigative Site

Debrecen, 4032, Hungary

Location

Novartis Investigative Site

Valencia, 46026, Spain

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Sepsis; Acute Kidney Injury

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2022
• First Posted: August 19, 2022
• Study Start: November 22, 2022
• Primary Completion: April 25, 2024
• Study Completion: April 25, 2024
• Last Updated: December 4, 2025
• Results First Posted: May 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

HU (1); FR (2); BE (2); ES (1); DE (1)