Last Update: Oct 01, 2024
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)
ClinicalTrials.gov Identifier:
Novartis Reference Number:CTIN816B12202
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

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). 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 sepsis and acute kidney injury (AKI). The study consists
of a screening period (24-48 hours), a treatment period (Day 1), and post-treatment
period (Day 2 to 90). Screening will take place during hospitalization in ICU (or
intermediate care unit/HDU) where potential participants will undergo screening to assess
the presence of sepsis and AKI. At Treatment Day 1, participants who meet eligibility
criteria at screening and baseline will be randomized in a 3:1:1:3 ratio to receive a
one-time treatment of TIN816 or placebo by intravenous infusion in a participant and
investigator-blinded fashion. Treatment Day 1 is followed by a 90-day post-treatment
period for safety and efficacy assessments. An interim analysis (IA) is planned when
approximately 120 participants complete Day 30 visit. A final analysis will be performed
after all participants have completed Day 90.

Acute Kidney Injury Due to Sepsis
Phase2
Recruiting
320
Jan 18, 2024
Feb 20, 2026
All
18 Years - 85 Years (Adult, Older Adult)

Interventions

Other

Placebo

0.9% sterile saline solution
Biological

TIN816 70 mg lyophilisate powder

Immunotherapy Recombinant human CD39 enzyme

Eligibility Criteria

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

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 Location

Novartis Investigative Site

Recruiting

Heidelberg,Victoria,3084,Australia

Novartis Investigative Site

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Herston,Queensland,4029,Australia

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Innsbruck,Tyrol,6020,Austria

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Ottignies,1340,Belgium

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Gent,9000,Belgium

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Salvador,40301-155,Brazil

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Sao Paulo,SP,01327 001,Brazil

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Curitiba,Parana,80010 030,Brazil

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Brasilia,DF,70390-140,Brazil

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Vancouver,British Columbia,V6z 1y6,Canada

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Kingston,Ontario,K7l 2v7,Canada

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Montreal,Quebec,H2w 1t8,Canada

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Montreal,Quebec,H4j 1c5,Canada

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Sainte Foy,Quebec,G1v 4g5,Canada

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Hangzhou,Zhejiang,310014,China

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Wuhan,430022,China

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Beijing,100730,China

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Zhengzhou,Henan,450003,China

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Guang Zhou,510260,China

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Limoges,Haute Vienne,87000,France

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Paris cedex 10,75010,France

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Nantes Cedex 1,44093,France

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Pessac Cedex,33604,France

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Argenteuil,95107,France

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Strasbourg Cedex,67091,France

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Garches,92380,France

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Le Kremlin Bicetre,94275,France

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Toulouse 4,31054,France

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Muenchen,81377,Germany

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Jena,07740,Germany

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Kiel,24105,Germany

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Stuttgart,70376,Germany

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Perugia,PG,06129,Italy

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Milano,MI,20100,Italy

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Roma,RM,00168,Italy

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Napoli,80131,Italy

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Milano,MI,20162,Italy

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Rozzano,MI,20089,Italy

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Bologna,BO,40138,Italy

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Padova,PD,35128,Italy

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Izumisano-city,Osaka,598-8577,Japan

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Valencia,46026,Spain

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Barcelona,Catalunya,08035,Spain

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Barcelona,08041,Spain

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Santiago De Compostela,Galicia,15706,Spain

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Madrid,28041,Spain

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Cordoba,Andalucia,14004,Spain

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Jerez,Cadiz,11407,Spain

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Sabadell,Barcelona,08208,Spain

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Chiang Mai,50200,Thailand

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Bangkok,10330,Thailand

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Bangkok,10400,Thailand

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Bangkok,10700,Thailand

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Ankara,06230,Turkey

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Istanbul,34093,Turkey

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Bristol,Bs2 8hw,United Kingdom

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Guildford,Surrey,Gu2 7xx,United Kingdom

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London,Se1 7eh,United Kingdom

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Recruiting

Birmingham,B15 2th,United Kingdom

Temple University Temple University

Recruiting

Philadelphia,Pennsylvania,19140,United States

Avrum Gillespie
Eric Lee

Northwestern Memorial Hospital Pulmonary and Critical Care

Recruiting

Evanston,Illinois,60611,United States

Francisco Martinez
Richard Wunderink

Mayo Clinic Rochester Main Centre

Recruiting

Rochester,Minnesota,55905,United States

Kianoush Kashani
Leah Knoke

Utah Intermountain Medical Center

Recruiting

Murray,Utah,84107,United States

Johnny Trang
Ithan Peltan

Good Samaritan Hospital

Recruiting

Corvallis,Oregon,97330,United States

Anthony Franklin
Brian Delmonaco

Wake Forest Univ School of Medicine U Health Sciences

Recruiting

Winston-Salem,North Carolina,27157-1071,United States

Ashish Khanna
Lynnette Harris

UC San Francisco Medical Center

Recruiting

San Francisco,California,94143-0116,United States

Aqsa Khan
Matthieu Legrand

Montefiore Medical Center

Recruiting

Bronx,New York,10461,United States

Luke Andrea
Ofelia Garcia

Henry Ford Hospital

Recruiting

Detroit,Michigan,48202 2689,United States

Karen Campana
Ryann Sohaney

Baylor Scott and White Research

Recruiting

Dallas,Texas,75246,United States

Ankit Mehta
Bradley Patterson

Univ Of Iowa Hospitals And Clinics

Recruiting

Iowa City,Iowa,52242,United States

Benjamin Griffin
Mc Lean Sunderland

Ohio State University Medical Center

Recruiting

Columbus,Ohio,43210,United States

Connor Lang
Matthew Exline

Montefiore Medical Center Montefiore Medical Center

Recruiting

Bronx,New York,10467,United States

Ari Moskowitz
Banafsaj Renaldi

Lahey Hospital and Medical Center

Recruiting

Burlington,Massachusetts,01805,United States

Christopher Hansen

Baystate Medical Center

Recruiting

Springfield,Massachusetts,01199,United States

Denise Gallant
Mark Tidswell

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