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

NCT ID: NCT05996835

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

320 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-18

Study Completion Date

2026-04-21

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Acute Kidney Injury Due to Sepsis

Keywords

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Sepsis acute kidney injury anti-inflammatory immunosuppression intensive care unit

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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TIN816 Dose A

Administered as a one time intravenous dose

Group Type EXPERIMENTAL

TIN816 70 mg lyophilisate powder

Intervention Type BIOLOGICAL

Immunotherapy Recombinant human CD39 enzyme

TIN816 Dose B

Administered as a one time intravenous dose

Group Type EXPERIMENTAL

TIN816 70 mg lyophilisate powder

Intervention Type BIOLOGICAL

Immunotherapy Recombinant human CD39 enzyme

TIN816 Dose C

Administered as a one time intravenous dose

Group Type EXPERIMENTAL

TIN816 70 mg lyophilisate powder

Intervention Type BIOLOGICAL

Immunotherapy Recombinant human CD39 enzyme

Placebo

0.9% sterile saline administered as a one time intravenous dose

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

0.9% sterile saline solution

Interventions

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TIN816 70 mg lyophilisate powder

Immunotherapy Recombinant human CD39 enzyme

Intervention Type BIOLOGICAL

Placebo

0.9% sterile saline solution

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Signed informed consent must be obtained in accordance with local regulations.
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

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.
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 (clinical diagnosis or positive infection serology), or 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.

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 \<30 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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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University Of Alabama

Birmingham, Alabama, United States

Site Status RECRUITING

UC San Francisco Medical Center

San Francisco, California, United States

Site Status RECRUITING

Stanford Healthcare

Stanford, California, United States

Site Status RECRUITING

Emory Johns Creek Hospital

Johns Creek, Georgia, United States

Site Status RECRUITING

Northwestern Memorial Hospital

Evanston, Illinois, United States

Site Status COMPLETED

Endeavor Health

Glenview, Illinois, United States

Site Status RECRUITING

Univ Of Iowa Hospitals And Clinics

Iowa City, Iowa, United States

Site Status RECRUITING

Univ Of Iowa Hospitals And Clinics

Iowa City, Iowa, United States

Site Status WITHDRAWN

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Beth Israel Deaconess Med Center

Boston, Massachusetts, United States

Site Status RECRUITING

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

Site Status RECRUITING

Baystate Medical Center

Springfield, Massachusetts, United States

Site Status RECRUITING

Henry Ford Hospital

Detroit, Michigan, United States

Site Status WITHDRAWN

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Montefiore Medical Center

The Bronx, New York, United States

Site Status RECRUITING

Montefiore Medical Center

The Bronx, New York, United States

Site Status RECRUITING

Wake Forest Univ School of Medicine

Winston-Salem, North Carolina, United States

Site Status RECRUITING

Ohio State University Medical Center

Columbus, Ohio, United States

Site Status RECRUITING

Good Samaritan Hospital

Corvallis, Oregon, United States

Site Status RECRUITING

Temple University

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

U Of Pittsburgh Med Ctr

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Baylor Scott and White

Dallas, Texas, United States

Site Status RECRUITING

Utah Intermountain Medical Center

Murray, Utah, United States

Site Status RECRUITING

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status RECRUITING

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status RECRUITING

Providence Med Resch Center and Chindren Hosp

Spokane, Washington, United States

Site Status WITHDRAWN

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Site Status RECRUITING

Novartis Investigative Site

Pilar, Buenos Aires, Argentina

Site Status RECRUITING

Novartis Investigative Site

CABA, , Argentina

Site Status RECRUITING

Novartis Investigative Site

Santa Fe, , Argentina

Site Status RECRUITING

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Herston, Queensland, Australia

Site Status RECRUITING

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Heidelberg, Victoria, Australia

Site Status RECRUITING

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Innsbruck, Tyrol, Austria

Site Status RECRUITING

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Genk, Limburg, Belgium

Site Status RECRUITING

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Brussels, , Belgium

Site Status RECRUITING

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Ghent, , Belgium

Site Status RECRUITING

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Ottignies, , Belgium

Site Status RECRUITING

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Brasília, Federal District, Brazil

Site Status RECRUITING

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Curitiba, Paraná, Brazil

Site Status RECRUITING

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Santo André, São Paulo, Brazil

Site Status RECRUITING

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São Paulo, São Paulo, Brazil

Site Status RECRUITING

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Salvador, , Brazil

Site Status RECRUITING

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Vancouver, British Columbia, Canada

Site Status RECRUITING

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Kingston, Ontario, Canada

Site Status WITHDRAWN

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Montreal, Quebec, Canada

Site Status RECRUITING

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Montreal, Quebec, Canada

Site Status RECRUITING

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Québec, Quebec, Canada

Site Status RECRUITING

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Shijiazhuang, Hebei, China

Site Status RECRUITING

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Zhengzhou, Henan, China

Site Status RECRUITING

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Hangzhou, Zhejiang, China

Site Status RECRUITING

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Beijing, , China

Site Status RECRUITING

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Guangzhou, , China

Site Status RECRUITING

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Wuhan, , China

Site Status RECRUITING

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Marseille, Bouches Du Rhone, France

Site Status RECRUITING

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Angers, France, France

Site Status RECRUITING

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Limoges, Haute Vienne, France

Site Status RECRUITING

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Argenteuil, , France

Site Status RECRUITING

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Garches, , France

Site Status RECRUITING

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Le Kremlin-Bicêtre, , France

Site Status RECRUITING

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Nantes, , France

Site Status RECRUITING

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Paris, , France

Site Status WITHDRAWN

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Pessac, , France

Site Status RECRUITING

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Strasbourg, , France

Site Status RECRUITING

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Toulouse, , France

Site Status RECRUITING

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Stuttgart, Baden-Wurttemberg, Germany

Site Status RECRUITING

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Munich, Bavaria, Germany

Site Status RECRUITING

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Frankfurt am Main, Hesse, Germany

Site Status RECRUITING

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Jena, Thuringia, Germany

Site Status RECRUITING

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Essen, , Germany

Site Status RECRUITING

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Kiel, , Germany

Site Status RECRUITING

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Münster, , Germany

Site Status RECRUITING

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Debrecen, Hajdu Bihar Megye, Hungary

Site Status RECRUITING

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Budapest, , Hungary

Site Status RECRUITING

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Győr, , Hungary

Site Status RECRUITING

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Székesfehérvár, , Hungary

Site Status RECRUITING

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Ahmedabad, Gujarat, India

Site Status RECRUITING

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Belagavi, Karnataka, India

Site Status RECRUITING

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Pune, Maharashtra, India

Site Status RECRUITING

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New Delhi, National Capital Territory of Delhi, India

Site Status RECRUITING

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Hyderabad, Telangana, India

Site Status RECRUITING

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Bologna, BO, Italy

Site Status RECRUITING

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Milan, MI, Italy

Site Status RECRUITING

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Milan, MI, Italy

Site Status RECRUITING

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Rozzano, MI, Italy

Site Status RECRUITING

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Padua, PD, Italy

Site Status RECRUITING

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Perugia, PG, Italy

Site Status WITHDRAWN

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Roma, RM, Italy

Site Status RECRUITING

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Napoli, , Italy

Site Status RECRUITING

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Kamogawa, Chiba, Japan

Site Status COMPLETED

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Asahikawa, Hokkaido, Japan

Site Status RECRUITING

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Yokohama, Kanagawa, Japan

Site Status RECRUITING

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Kumamoto, Kumamoto, Japan

Site Status RECRUITING

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Izumisano, Osaka, Japan

Site Status RECRUITING

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Osaka, Osaka, Japan

Site Status RECRUITING

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Ureshino, Saga-ken, Japan

Site Status ACTIVE_NOT_RECRUITING

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Izumo, Shimane, Japan

Site Status RECRUITING

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Hachiōji, Tokyo, Japan

Site Status RECRUITING

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Itabashi-ku, Tokyo, Japan

Site Status RECRUITING

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Fukuoka, , Japan

Site Status RECRUITING

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Kumamoto, , Japan

Site Status RECRUITING

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Pretoria, , South Africa

Site Status RECRUITING

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Santiago Compostela, A Coruna, Spain

Site Status WITHDRAWN

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status WITHDRAWN

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Sabadell, Barcelona, Spain

Site Status RECRUITING

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Jerez de la Frontera, Cadiz, Spain

Site Status WITHDRAWN

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Terrassa, Catalonia, Spain

Site Status WITHDRAWN

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Barcelona, , Spain

Site Status RECRUITING

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Barcelona, , Spain

Site Status RECRUITING

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Córdoba, , Spain

Site Status RECRUITING

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Madrid, , Spain

Site Status RECRUITING

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Madrid, , Spain

Site Status RECRUITING

Novartis Investigative Site

Valencia, , Spain

Site Status RECRUITING

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Bangkok, , Thailand

Site Status RECRUITING

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Bangkok, , Thailand

Site Status RECRUITING

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Bangkok, , Thailand

Site Status RECRUITING

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Chiang Mai, , Thailand

Site Status RECRUITING

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Istanbul, Fatih, Turkey (Türkiye)

Site Status WITHDRAWN

Novartis Investigative Site

Ankara, Sihhiye-Altindag, Turkey (Türkiye)

Site Status WITHDRAWN

Novartis Investigative Site

Guildford, Surrey, United Kingdom

Site Status WITHDRAWN

Novartis Investigative Site

Birmingham, West Midlands, United Kingdom

Site Status RECRUITING

Novartis Investigative Site

Bristol, , United Kingdom

Site Status WITHDRAWN

Novartis Investigative Site

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Argentina Australia Austria Belgium Brazil Canada China France Germany Hungary India Italy Japan South Africa Spain Thailand Turkey (Türkiye) United Kingdom

Central Contacts

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Novartis Pharmaceuticals

Role: CONTACT

Phone: 1-888-669-6682

Email: [email protected]

Novartis Pharmaceuticals

Role: CONTACT

Phone: +41613241111

Facility Contacts

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Aleena Asif

Role: primary

Aqsa Khan

Role: primary

Kelley Logan

Role: primary

Amy Anderson

Role: primary

Catherine Futoransky

Role: primary

Mc Lean Sunderland

Role: primary

Sydney Olafsen

Role: primary

Carlo Ottanelli

Role: primary

Caroline Schissel

Role: primary

Lesley Desouza

Role: primary

Mitchell Strand

Role: primary

Brenda Lopez

Role: primary

Daniel Ceusters

Role: primary

Tanmay Sura

Role: primary

Sarah Karow

Role: primary

Kristen Moylan

Role: primary

Ellen Bedenko

Role: primary

Tina Vita

Role: primary

Daniela Gonzalez

Role: primary

Jose Romero

Role: primary

Kedir Seid

Role: primary

Shawn Fenner

Role: primary

Other Identifiers

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CTIN816B12202

Identifier Type: -

Identifier Source: org_study_id