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

NCT05996835 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: CTIN816B12202
• Study Type: interventional
• Target: 316
• Locations: 16 countries
• Sites: 78

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 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; anti-inflammatory; immunosuppression; intensive care unit

Outcome Measures

Primary Outcomes (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.

  Day 1 to Day 8

Secondary Outcomes (10)

• Percentage of participants with major adverse kidney events (MAKE)

  Day 1 to Day 90

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

  Day 1 to Day 14 and Day 1 to Day 30

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

  Day 1 to Day 14 and Day 1 to Day 30

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

  Day 5 to Day 14

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

  Day 1 to Day 90

Study Arms (4)

TIN816 Dose A

EXPERIMENTAL

Administered as a one time intravenous dose

Biological: TIN816 70 mg lyophilisate powder

TIN816 Dose B

EXPERIMENTAL

Administered as a one time intravenous dose

Biological: TIN816 70 mg lyophilisate powder

TIN816 Dose C

EXPERIMENTAL

Administered as a one time intravenous dose

Biological: TIN816 70 mg lyophilisate powder

Placebo

PLACEBO COMPARATOR

0.9% sterile saline administered as a one time intravenous dose

Other: Placebo

Interventions

Placebo OTHER

0.9% sterile saline solution

Placebo

TIN816 70 mg lyophilisate powder BIOLOGICAL

Immunotherapy Recombinant human CD39 enzyme

TIN816 Dose A; TIN816 Dose B; TIN816 Dose C

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 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

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 \<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.
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (79)

University Of Alabama

Birmingham, Alabama, 35233, United States

Location

UC San Francisco Medical Center

San Francisco, California, 94143-0116, United States

Location

Stanford Healthcare

Stanford, California, 94305 5152, United States

Location

Emory Johns Creek Hospital

Johns Creek, Georgia, 30097, United States

Location

Northwestern Memorial Hospital

Evanston, Illinois, 60611, United States

Location

Univ Of Iowa Hospitals And Clinics

Iowa City, Iowa, 52242, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Med Center

Boston, Massachusetts, 02215, United States

Location

Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Wake Forest Univ School of Medicine

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

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Good Samaritan Hospital

Corvallis, Oregon, 97330, United States

Location

U Of Pittsburgh Med Ctr

Pittsburgh, Pennsylvania, 15213, United States

Location

Baylor Scott and White

Dallas, Texas, 75246, United States

Location

Utah Intermountain Medical Center

Murray, Utah, 84107, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1118AAT, Argentina

Location

Novartis Investigative Site

Pilar, Buenos Aires, B1629AHJ, Argentina

Location

Novartis Investigative Site

CABA, C1181ACH, Argentina

Location

Novartis Investigative Site

Heidelberg, Victoria, 3084, Australia

Location

Novartis Investigative Site

Innsbruck, Tyrol, 6020, Austria

Location

Novartis Investigative Site

Genk, Limburg, 3600, Belgium

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Ghent, 9000, Belgium

Location

Novartis Investigative Site

Ottignies, 1340, Belgium

Location

Novartis Investigative Site

São Paulo, São Paulo, 01327 001, Brazil

Location

Novartis Investigative Site

Salvador, 40323-010, Brazil

Location

Novartis Investigative Site

Montreal, Quebec, H2W 1T8, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H4J 1C5, Canada

Location

Novartis Investigative Site

Québec, Quebec, G1V 4G5, Canada

Location

Novartis Investigative Site

Shijiazhuang, Hebei, 050011, China

Location

Novartis Investigative Site

Beijing, 100730, China

Location

Novartis Investigative Site

Guangzhou, 510260, China

Location

Novartis Investigative Site

Wuhan, 430022, China

Location

Novartis Investigative Site

Limoges, Haute Vienne, 87000, France

Location

Novartis Investigative Site

Argenteuil, 95107, France

Location

Novartis Investigative Site

Garches, 92380, France

Location

Novartis Investigative Site

Le Kremlin-Bicêtre, 94275, France

Location

Novartis Investigative Site

Nantes, 44093, France

Location

Novartis Investigative Site

Pessac, 33604, France

Location

Novartis Investigative Site

Strasbourg, 67091, France

Location

Novartis Investigative Site

Toulouse, 31054, France

Location

Novartis Investigative Site

Munich, Bavaria, 81377, Germany

Location

Novartis Investigative Site

Frankfurt am Main, Hesse, 60590, Germany

Location

Novartis Investigative Site

Jena, Thuringia, 07740, Germany

Location

Novartis Investigative Site

Kiel, 24105, Germany

Location

Novartis Investigative Site

Münster, 48149, Germany

Location

Novartis Investigative Site

Győr, H-9024, Hungary

Location

Novartis Investigative Site

Ahmedabad, Gujarat, 380060, India

Location

Novartis Investigative Site

Belagavi, Karnataka, 590010, India

Location

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, 110001, India

Location

Novartis Investigative Site

Hyderabad, Telangana, 500034, India

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Padova, PD, 35128, Italy

Location

Novartis Investigative Site

Roma, RM, 00168, Italy

Location

Novartis Investigative Site

Naples, 80131, Italy

Location

Novartis Investigative Site

Kamogawa, Chiba, 296-8602, Japan

Location

Novartis Investigative Site

Yokohama, Kanagawa, 245-8575, Japan

Location

Novartis Investigative Site

Kumamoto, Kumamoto, 860-0008, Japan

Location

Novartis Investigative Site

Izumisano, Osaka, 5988577, Japan

Location

Novartis Investigative Site

Osaka, Osaka, 5340021, Japan

Location

Novartis Investigative Site

Ureshino, Saga-ken, 843-0393, Japan

Location

Novartis Investigative Site

Izumo, Shimane, 693-8555, Japan

Location

Novartis Investigative Site

Hachiōji, Tokyo, 193-0998, Japan

Location

Novartis Investigative Site

Itabashi-ku, Tokyo, 1738610, Japan

Location

Novartis Investigative Site

Sabadell, Barcelona, 08208, Spain

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Barcelona, 08041, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Valencia, 46026, Spain

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Chiang Mai, 50200, Thailand

Location

Novartis Investigative Site

Birmingham, West Midlands, B15 2TH, United Kingdom

Location

Novartis Investigative Site

London, SE1 7EH, United Kingdom

Location

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

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

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 10, 2023
• First Posted: August 18, 2023
• Study Start: January 18, 2024
• Primary Completion: February 25, 2026
• Study Completion: May 14, 2026
• Last Updated: June 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

GB (2); IN (4); AU (1); BR (2); AR (3); IT (4); DE (5); FR (8); CA (3); US (19); CN (4); ES (6); BE (4); JP (9); TH (3); HU (1)