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Acute Kidney Injury Due to SepsisPhase 2CLEAR-AKINCT05996835

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

A Phase 2 study testing TIN816 70 mg lyophilisate powder in people with Acute Kidney Injury Due to Sepsis, run by Novartis Pharmaceuticals at 79 sites in 17 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 an intensive care setting with a diagnosis of sepsis-associated acute kidney injury (SA-AKI). Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Acute Kidney Injury Due to Sepsis
What is being tested?
TIN816 70 mg lyophilisate powder
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
316 participants
Where
79 sitesin 17 countries
Study dates
18 Jan 2024to 14 May 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 13Show fewer
  • 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

Who cannot join

  • 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.
Show all 31Show fewer
  • 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.

Trial locations and contacts

79 sites in 17 countries.

79 sites in 17 countries

United States19 sites

  • University Of Alabama

    Birmingham, Alabama, 35233

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Med Center

    Boston, Massachusetts, 02215

  • Lahey Hospital and Medical Center

    Burlington, Massachusetts, 01805

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • Good Samaritan Hospital

    Corvallis, Oregon, 97330

  • Baylor Scott and White

    Dallas, Texas, 75246

  • Northwestern Memorial Hospital

    Evanston, Illinois, 60611

  • Univ Of Iowa Hospitals And Clinics

    Iowa City, Iowa, 52242

  • Emory Johns Creek Hospital

    Johns Creek, Georgia, 30097

  • Utah Intermountain Medical Center

    Murray, Utah, 84107

  • U Of Pittsburgh Med Ctr

    Pittsburgh, Pennsylvania, 15213

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

  • UC San Francisco Medical Center

    San Francisco, California, 94143-0116

  • Baystate Medical Center

    Springfield, Massachusetts, 01199

  • Stanford Healthcare

    Stanford, California, 94305 5152

  • Montefiore Medical Center

    The Bronx, New York, 10461

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • Wake Forest Univ School of Medicine

    Winston-Salem, North Carolina, 27157-1071

Other trials in United States

Japan9 sites

  • Novartis Investigative Site

    Hachiōji, Tokyo, 193-0998

  • Novartis Investigative Site

    Izumisano, Osaka, 5988577

  • Novartis Investigative Site

    Izumo, Shimane, 693-8555

  • Novartis Investigative Site

    Kamogawa, Chiba, 296-8602

  • Novartis Investigative Site

    Kumamoto, Kumamoto, 860-0008

  • Novartis Investigative Site

    Osaka, Osaka, 5340021

  • Novartis Investigative Site

    tabashi City, Tokyo, 1738610

  • Novartis Investigative Site

    Ureshino, Saga-ken, 843-0393

  • Novartis Investigative Site

    Yokohama, Kanagawa, 245-8575

Other trials in Japan

France8 sites

  • Novartis Investigative Site

    Argenteuil, 95107

  • Novartis Investigative Site

    Garches, 92380

  • Novartis Investigative Site

    Le Kremlin-Bicêtre, 94275

  • Novartis Investigative Site

    Limoges, Haute Vienne, 87000

  • Novartis Investigative Site

    Nantes, 44093

  • Novartis Investigative Site

    Pessac, 33604

  • Novartis Investigative Site

    Strasbourg, 67091

  • Novartis Investigative Site

    Toulouse, 31054

Other trials in France

Spain6 sites

  • Novartis Investigative Site

    Barcelona, 08035

  • Novartis Investigative Site

    Barcelona, 08041

  • Novartis Investigative Site

    Madrid, 28040

  • Novartis Investigative Site

    Madrid, 28041

  • Novartis Investigative Site

    Sabadell, Barcelona, 08208

  • Novartis Investigative Site

    Valencia, 46026

Other trials in Spain

Germany5 sites

  • Novartis Investigative Site

    Frankfurt am Main, Hesse, 60590

  • Novartis Investigative Site

    Jena, Thuringia, 07740

  • Novartis Investigative Site

    Kiel, 24105

  • Novartis Investigative Site

    Munich, Bavaria, 81377

  • Novartis Investigative Site

    Münster, 48149

Other trials in Germany

Belgium4 sites

  • Novartis Investigative Site

    Brussels, 1200

  • Novartis Investigative Site

    Genk, Limburg, 3600

  • Novartis Investigative Site

    Ghent, 9000

  • Novartis Investigative Site

    Ottignies, 1340

Other trials in Belgium

China4 sites

  • Novartis Investigative Site

    Beijing, 100730

  • Novartis Investigative Site

    Guangzhou, 510260

  • Novartis Investigative Site

    Shijiazhuang, Hebei, 050011

  • Novartis Investigative Site

    Wuhan, 430022

Other trials in China

India4 sites

  • Novartis Investigative Site

    Ahmedabad, Gujarat, 380060

  • Novartis Investigative Site

    Belagavi, Karnataka, 590010

  • Novartis Investigative Site

    Hyderabad, Telangana, 500034

  • Novartis Investigative Site

    New Delhi, National Capital Territory of Delhi, 110001

Other trials in India

Italy4 sites

  • Novartis Investigative Site

    Naples, 80131

  • Novartis Investigative Site

    Padova, PD, 35128

  • Novartis Investigative Site

    Roma, RM, 00168

  • Novartis Investigative Site

    Rozzano, MI, 20089

Other trials in Italy

Argentina3 sites

  • Novartis Investigative Site

    CABA, Buenos Aires, C1118AAT

  • Novartis Investigative Site

    CABA, C1181ACH

  • Novartis Investigative Site

    Pilar, Buenos Aires, B1629AHJ

Other trials in Argentina

Canada3 sites

  • Novartis Investigative Site

    Montreal, Quebec, H2X 1R9

  • Novartis Investigative Site

    Montreal, Quebec, H4J 1C5

  • Novartis Investigative Site

    Québec, Quebec, G1V 4G5

Other trials in Canada

Thailand3 sites

  • Novartis Investigative Site

    Bangkok, 10330

  • Novartis Investigative Site

    Bangkok, 10700

  • Novartis Investigative Site

    Chiang Mai, 50200

Other trials in Thailand

Brazil2 sites

  • Novartis Investigative Site

    Salvador, 40323-010

  • Novartis Investigative Site

    São Paulo, São Paulo, 01327 001

Other trials in Brazil

United Kingdom2 sites

  • Novartis Investigative Site

    Birmingham, West Midlands, B15 2TH

  • Novartis Investigative Site

    London, SE1 7EH

Other trials in United Kingdom

Australia1 site

  • Novartis Investigative Site

    Heidelberg, Victoria, 3084

Other trials in Australia

Austria1 site

  • Novartis Investigative Site

    Innsbruck, Tyrol, 6020

Other trials in Austria

Hungary1 site

  • Novartis Investigative Site

    Győr, H-9024

Other trials in Hungary

About this study

Official 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 (CLEAR-AKI)

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).

Read the 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 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.

Being tested
TIN816 70 mg lyophilisate powder, Placebo
Keywords
Sepsis, acute kidney injury, anti-inflammatory, immunosuppression, intensive care unit
Medical subject headings
Sepsis, Acute Kidney Injury

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TIN816 70 mg lyophilisate powderBiological

    Immunotherapy Recombinant human CD39 enzyme

  • PlaceboOther

    0.9% sterile saline solution

Study groups in NCT05996835
Study groupRoleWhat they receive
TIN816 Dose AExperimentalAdministered as a one time intravenous dose
Receives: Biological: TIN816 70 mg lyophilisate powder
TIN816 Dose BExperimentalAdministered as a one time intravenous dose
Receives: Biological: TIN816 70 mg lyophilisate powder
TIN816 Dose CExperimentalAdministered as a one time intravenous dose
Receives: Biological: TIN816 70 mg lyophilisate powder
PlaceboPlacebo comparator0.9% sterile saline administered as a one time intravenous dose
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Average of area under the time-corrected creatinine clearance curve (AUC1-8)

    The weighted average of area under the time-corrected endogenous creatinine clearance curve.

    Urine volume, urinary creatinine, and the serum creatinine measurements will be used for calculation. Day 1-8 measurements will be included.

    Measured: Day 1 to Day 8

Secondary outcomes (10)

  1. Percentage of participants with major adverse kidney events (MAKE)

    A binary composite endpoint of major adverse kidney events (MAKE) including death, use of Renal Replacement Therapy (RRT) and ≥25% reduction from reference in estimated Glomular Filtration Rate (eGFR) at Day 90.

    Measured: Day 1 to Day 90

  2. Area under the time-corrected endogenous serum creatinine curve for Day 1 to Day 14 and Day 1 to Day 30.

    The weighted average of area under the time-corrected endogenous serum creatinine curve from Day 1 to Day 14 and Day 1 to Day 30.

    Measured: Day 1 to Day 14 and Day 1 to Day 30

  3. Area under the time-corrected endogenous serum cystatin C curve for Day 1 to Day 14 and Day 1 to Day 30

    The weighted average of area under the time-corrected endogenous serum cystatin-C curve from Day 1 to Day 14 and Day 1 to Day 30.

    Measured: Day 1 to Day 14 and Day 1 to Day 30

  4. Area under the time-corrected creatinine clearance curve (AUC5-14)

    The weighted average of area under the time-corrected endogenous creatinine clearance curve.

    Urine volume, urinary creatinine, and the serum creatinine measurements will be used for calculation. Day 5-14 measurements will be included.

    Measured: Day 5 to Day 14

  5. Percentage of participants who had renal replacement therapy (RRT) from Day 1 to Day 90

    Use of RRT at any time during the treatment period will be reported.

    Measured: Day 1 to Day 90

  6. Percentage of participants with RRT dependency at Day 90

    Use of RRT dependency at Day 90 will be reported

    Measured: Day 90

  7. Number of days participants alive and free of RRT from Day 1 to Day 90

    Participants who are alive and free of RRT, defined as any participant receiving any form of RRT, will be reported.

    Measured: Day 1 to Day 90

  8. Change in Kidney disease improving global outcomes (KDIGO) score from Baseline to Day 14

    The KDIGO classification system stages AKI into three levels based on serum creatinine elevation in parallel with degree and duration of oliguria. Participants are classified based on the worst finding (either serum creatinine or oliguria). The stages range from 1-3, with higher scores indicating the most severe stage of AKI.

    Measured: 14 Days

  9. Percentage of participants with ≥25% reduction in eGFR at Day 90

    Percentage of participants with ≥ 25% reduction from reference to Day 90.

    Measured: 90 Days

  10. Mean change of sequential organ failure assessment score (SOFA) from baseline to Day 30

    The SOFA score was developed to assess the acute morbidity of critical illness at a population level. The score is routinely calculated on admission to ICU and at each 24-hour period that follows. It is composed of six criteria which reflect the function of a specific organ system (respiratory, cardiovascular, renal, neurological, hepatic and hematological) and allocates a score of 0-4.

    Scores ranges from 0-24, with higher scores indicating greater dysfunction.

    Measured: 30 Days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Aug 2023
  2. Study start18 Jan 2024
  3. Primary completion25 Feb 2026
  4. Study completion14 May 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
316 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05996835
Sponsor's protocol ID
CTIN816B12202
Other IDs
2023-505903-22-00, 2023
Acronym
CLEAR-AKI
Status last verified
Jul 2026
First submitted
10 Aug 2023
Last updated
29 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TIN816 70 mg lyophilisate powder in people with Acute Kidney Injury Due to Sepsis, run by Novartis Pharmaceuticals at 79 sites in 17 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 79 sites in United States, Japan, France, Spain, Germany and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Average of area under the time-corrected creatinine clearance curve (AUC1-8) (time frame: Day 1 to Day 8). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05996835.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2026.

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