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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05996835




Registration number
NCT05996835
Ethics application status
Date submitted
10/08/2023
Date registered
18/08/2023

Titles & IDs
Public title
Phase 2b Study to Investigate the Safety and Efficacy of TIN816 in Sepsis-associated Acute Kidney Injury (SA-AKI)
Scientific title
A Multicenter, Randomized, Double-blind, Placebo-controlled, Four-arm, Parallel-group, Dose-finding Phase 2b Study to Investigate the Safety and Efficacy of TIN816 Via a Single Intravenous Infusion in the Treatment of Participants With Sepsis-associated Acute Kidney Injury (SA-AKI)
Secondary ID [1] 0 0
CTIN816B12202
Universal Trial Number (UTN)
Trial acronym
CLEAR-AKI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Kidney Injury Due to Sepsis 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Injuries and Accidents 0 0 0 0
Poisoning
Blood 0 0 0 0
Other blood disorders
Infection 0 0 0 0
Other infectious diseases
Renal and Urogenital 0 0 0 0
Kidney disease
Injuries and Accidents 0 0 0 0
Other injuries and accidents
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - TIN816 70 mg lyophilisate powder
Other interventions - Placebo

Experimental: TIN816 Dose A - Administered as a one time intravenous dose

Experimental: TIN816 Dose B - Administered as a one time intravenous dose

Experimental: TIN816 Dose C - Administered as a one time intravenous dose

Placebo comparator: Placebo - 0.9% sterile saline administered as a one time intravenous dose


Treatment: Other: TIN816 70 mg lyophilisate powder
Immunotherapy Recombinant human CD39 enzyme

Other interventions: Placebo
0.9% sterile saline solution
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Average of area under the time-corrected creatinine clearance curve (AUC1-8)
Timepoint [1] 0 0
Day 1 to Day 8
Secondary outcome [1] 0 0
Percentage of participants with major adverse kidney events (MAKE)
Timepoint [1] 0 0
Day 1 to Day 90
Secondary outcome [2] 0 0
Area under the time-corrected endogenous serum creatinine curve for Day 1 to Day 14 and Day 1 to Day 30.
Timepoint [2] 0 0
Day 1 to Day 14 and Day 1 to Day 30
Secondary outcome [3] 0 0
Area under the time-corrected endogenous serum cystatin C curve for Day 1 to Day 14 and Day 1 to Day 30
Timepoint [3] 0 0
Day 1 to Day 14 and Day 1 to Day 30
Secondary outcome [4] 0 0
Area under the time-corrected creatinine clearance curve (AUC5-14)
Timepoint [4] 0 0
Day 5 to Day 14
Secondary outcome [5] 0 0
Percentage of participants who had renal replacement therapy (RRT) from Day 1 to Day 90
Timepoint [5] 0 0
Day 1 to Day 90
Secondary outcome [6] 0 0
Percentage of participants with RRT dependency at Day 90
Timepoint [6] 0 0
Day 90
Secondary outcome [7] 0 0
Number of days participants alive and free of RRT from Day 1 to Day 90
Timepoint [7] 0 0
Day 1 to Day 90
Secondary outcome [8] 0 0
Change in Kidney disease improving global outcomes (KDIGO) score from Baseline to Day 14
Timepoint [8] 0 0
14 Days
Secondary outcome [9] 0 0
Percentage of participants with =25% reduction in eGFR at Day 90
Timepoint [9] 0 0
90 Days
Secondary outcome [10] 0 0
Mean change of sequential organ failure score (SOFA) from baseline to Day 30
Timepoint [10] 0 0
30 Days

Eligibility
Key inclusion criteria
1. Signed informed consent must be obtained prior to participation in the study.
2. = 18 to = 85 years of age
3. Admitted to ICU or intermediate care unit/ high dependency care unit (HDU)
4. 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
5. 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:

1. The most recent value within 3 months of the hospital admission. If not available:
2. The most recent value between 3 and 12 months prior to hospital admission. If not available:
3. At hospital admission
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria

1. Not expected to survive for 24 hours
2. Not expected to survive for 30 days due to medical conditions other than SA-AKI
3. History of CKD with a documented estimated GFR <45 mL/min prior to admission to hospital
4. eGFR <45mL/min at admission without any other reference serum eGFR within last 12-months
5. Receiving RRT or a decision has been made to initiate RRT within 24 hours after randomization
6. Weight is less than 40 kg or more than 125 kg.
7. 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)
8. Sepsis diagnosis according to sepsis inclusion criteria for a period longer than 72 hours prior to ICU admission
9. AKI diagnosis according to AKI inclusion criteria over 48 hours after admission to ICU
10. Inability to administer study drug within 24 hours of diagnosis of AKI according to AKI inclusion criteria
11. 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
12. Evidence of recovery from AKI based on the investigator's clinical judgement prior to randomization
13. 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
14. 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)
15. Patients who are post-nephrectomy
16. Patients with permanent incapacitation
17. 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.)
18. 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. See Appendix Section 10.6 Immunosuppresant drugs, (Table 10 5 Immunosuppressant drug exclusions)
19. 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
20. Known active hepatitis B or C infection, or positive Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) serology or patients with advanced chronic liver disease, confirmed by a Child-Pugh score of 10-15 (Class C)
21. Acute pancreatitis with no established source of infection
22. Active hematological malignancy (previous hematological malignancies that are not actively treated are allowable)
23. Burns requiring ICU treatment
24. Sepsis attributed to confirmed COVID-19
25. 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
26. History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes
27. Any medical conditions that could significantly increase risk of participants' safety by participating in this study according to investigator's judgement
28. Women with a positive pregnancy test, pregnancy or breast feeding
29. Women of childbearing potential, unless they are using highly effective methods of contraception for the entire duration of the trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/01/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
20/02/2026
Actual
Sample size
Target
320
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Herston
Recruitment hospital [2] 0 0
Novartis Investigative Site - Heidelberg
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
Iowa
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Utah
Country [12] 0 0
Austria
State/province [12] 0 0
Innsbruck
Country [13] 0 0
Belgium
State/province [13] 0 0
Gent
Country [14] 0 0
Belgium
State/province [14] 0 0
Ottignies
Country [15] 0 0
Brazil
State/province [15] 0 0
Parana
Country [16] 0 0
Brazil
State/province [16] 0 0
Salvador
Country [17] 0 0
Canada
State/province [17] 0 0
British Columbia
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
China
State/province [20] 0 0
Zhejiang
Country [21] 0 0
China
State/province [21] 0 0
Beijing
Country [22] 0 0
China
State/province [22] 0 0
Guang Zhou
Country [23] 0 0
China
State/province [23] 0 0
Wuhan
Country [24] 0 0
France
State/province [24] 0 0
Le Kremlin Bicetre
Country [25] 0 0
France
State/province [25] 0 0
Limoges
Country [26] 0 0
France
State/province [26] 0 0
Nantes Cedex 1
Country [27] 0 0
France
State/province [27] 0 0
Paris cedex 10
Country [28] 0 0
France
State/province [28] 0 0
Strasbourg Cedex
Country [29] 0 0
France
State/province [29] 0 0
Toulouse 4
Country [30] 0 0
Italy
State/province [30] 0 0
MI
Country [31] 0 0
Italy
State/province [31] 0 0
RM
Country [32] 0 0
Italy
State/province [32] 0 0
Napoli
Country [33] 0 0
Spain
State/province [33] 0 0
Barcelona
Country [34] 0 0
Spain
State/province [34] 0 0
Cadiz
Country [35] 0 0
Spain
State/province [35] 0 0
Galicia
Country [36] 0 0
Spain
State/province [36] 0 0
Madrid
Country [37] 0 0
Spain
State/province [37] 0 0
Valencia
Country [38] 0 0
Thailand
State/province [38] 0 0
Bangkok
Country [39] 0 0
Thailand
State/province [39] 0 0
Chiang Mai
Country [40] 0 0
Turkey
State/province [40] 0 0
Ankara
Country [41] 0 0
Turkey
State/province [41] 0 0
Istanbul
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Surrey
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Birmingham
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Bristol
Country [45] 0 0
United Kingdom
State/province [45] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05996835