A multi-center study to evaluate the safety, tolerability and efficacy of TIN816 in patients at risk for acute kidney injury following a cardiac surgery.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

18 Jan 2023 → 23 Jun 2025

Decision date (initial)

2024-08-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2024-511621-64-00

EudraCT number

2022-000794-47

ClinicalTrials.gov

NCT05524051

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenetic, Safety, Pharmacodynamic, Others, Pharmacokinetic, Therapy

To assess the effect of TIN816 on serum creatinine levels in patients at high risk for AKI
and undergoing major cardio-vascular surgery, versus placebo

Secondary objectives 4

1. To evaluate the safety and tolerability of TIN816
2. To assess the effect of TIN816 on the incidence and severity of AKI in patients at high risk for AKI and undergoing major cardio-vascular surgery, versus placebo.
3. To assess immunogenicity of TIN816
4. To assess the effect of TIN816 on the incidence of acute kidney disease (AKD) in high-risk patients undergoing major cardio-vascular surgery, versus placebo

Conditions and MedDRA coding

Acute kidney injury

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board, Federal Institute For Drugs And Medical Devices, Federal Agency For Medicines And Health Products

Plan to share IPD

Yes

IPD plan description

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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Signed informed consent must be obtained prior to participation in the study. Article I. Participants must be able to communicate well with the investigator and to understand and comply with the requirements of the study. Article II. Male and female patients ≥45 years at screening Article III. Participants must weigh at least 50 kg and maximum 150 kg to participate in the study and must have a body mass index (BMI) below 40. BMI = Body weight (kg) /[Height (m)]2
2. At screening, vital signs should be assessed in the sitting or supine position and be within the following ranges: a. body temperature between 35.0-37.5 °C b. blood pressure (systolic 100-160 mmHg, diastolic < 100 mmHg) c. pulse rate (50-100/min) stable with or without medication(s) as per Investigator‘s assessment. If vital signs are outside these ranges, the Investigator may obtain two additional readings, so that up to three consecutive assessments are made. At least the last reading must be within the ranges provided above for the participant to qualify.
3. Stable renal function with no known increase in SCr of ≥25% at screening visit compared to a previous value obtained within the last 6 months as documented by a local laboratory using standard assay methodology, and no AKI present (any stage) at pre-surgery baseline at discretion of the investigator.
4. Non-emergent open chest cavity major cardiopulmonary bypass (CPB) surgery with expected CPB time ≥1 hour

Exclusion criteria 7

1. eGFR at screening <15 mL/min/1.73 m2 (calculated using CKD-EPI 2021 equation)
2. Receiving renal replacement therapy (RRT) currently or at any time within 3 months prior to screening, or scheduled to start RRT shortly after cardiac surgery.
3. Patients with bleeding risk at screening, or identified as such pre-surgery if screening was performed earlier than Day -1. The Investigator should make this determination in consideration of the participant's medical history and/or clinical or laboratory evidence of any of the following: • History of bleeding with suspected or confirmed bleeding disorder or any other high risk for bleeding in the opinion of the investigator • Thrombocytopenia: platelet count <100x109/L • History of platelet dysfunction e.g., ADP induced platelet aggregation lower than 60% • History of coagulation factor deficiencies, including but not limited to fibrinogen ≤ 2.5 g/L or Von Willebrand factor (vWF) ≤ 50 IU/dL.
4. Duration of cardiopulmonary bypass (CPB) <60 minutes
5. Patient with active bleeding at the end of the surgery as per assessment of the leading surgeon
6. Donation or loss of >450 mL of blood or > 200 mL of plasma within four weeks prior to dosing, or longer if required by local regulation
7. Scheduled to undergo cardiac surgery off CPB or with hypothermic circulatory arrest or scheduled to undergo TAVI or TAVR only or single vessel, minimally invasive direct coronary artery bypass (MIDCAB) off-pump surgeries or left ventricular assist device (LVAD) implantation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Ratio of the highest serum creatinine value (up to and including Study Day 6) versus baseline

Secondary endpoints 4

1. Safety based on vital signs, physical examination, ECGs, laboratory assessments and collection of AEs assessed from baseline until the end of the study visit
2. AKI stages 1, 2 and 3 as defined by modified AKI Network (AKIN) criteria for serum creatinine
3. Anti-drug antibodies against TIN816
4. Occurrence of major adverse kidney events at day 30 (MAKE30) and day 90 (MAKE90) Occurrence of individual components of the MAKE criteria at Days 30 or 90.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 17

Locations

7 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Documents 60 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications