Phase 2b study to investigate the safety and efficacy of TIN816 in SA-AKI

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

2 Jul 2024 → 14 May 2026

Decision date (initial)

2024-05-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-505903-22-00

ClinicalTrials.gov

NCT05996835

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Pharmacokinetic, Dose response, Safety

To evaluate the dose response relationship of TIN816 on renal function measured by creatinine clearance (CrCl) in participants with Sepsis-associated Acute Kidney Injury

Secondary objectives 4

1. - to evaluate the effect of TIN816 versus placebo in reducing major adverse kidney events (MAKE)
2. - to evaluate the effect of TIN816 versus placebo in improving renal function
3. - to evaluate the effect of TIN816 versus placebo in improving overall health condition
4. - to evaluate safety and tolerability of TIN816 versus placebo

Conditions and MedDRA coding

Sepsis associated acute kidney injury

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

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. 1. ≥ 18 to ≤ 85 years of age
2. 2. Admitted to ICU or intermediate care unit/ high dependency care unit (HDU)
3. 3. 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 patients known to have pre-existing (acute or chronic) organ dysfunction before the onset of infection.
4. 4. 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 pre-sepsis creatinine. • For patients 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 patients presenting from community, the reference pre-sepsis 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 10

1. 3. 3. History of CKD with a documented estimated GFR < 30 ml/min prior to admission to hospital
2. 4. eGFR <45ml/min at admission without any other reference serum eGFR within last 12-months
3. 5. Receiving RRT or a decision has been made to initiate RRT within 24 hours after randomization.
4. 8. Sepsis diagnosis according to sepsis inclusion criteria for a period longer than 72 hours prior to ICU admission.
5. 9. AKI diagnosis according to AKI inclusion criteria over 48 hours after admission to ICU.
6. 10. Inability to administer study drug within 24 hours of diagnosis of AKI according to AKI inclusion criteria.
7. 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.
8. 12. Evidence of recovery from AKI based on the investigator’s clinical judgement prior to randomization.
9. 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).
10. 16. Patients who are thrombocytopenic at screening (platelet count <50,000 per microliter) or other high risk for bleeding in the opinion of the investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The weighted average of area under the time-corrected endogenous creatinine clearance curve from Day 1 to Day 8 (AUC1-8).

Secondary endpoints 4

1. Composite endpoint of major adverse kidney events (MAKE) including death, use of RRT and ≥25% reduction from reference in eGFR at Day 90
2. The weighted average of area under the time-corrected endogenous serum creatinine and endogenous serum cystatin C curve from Day1 to Day14 and Day1 to Day30 The weighted average of area under the time-corrected endogenous creatinine clearance curve from Day5 to Day14 (AUC5-14). Any use of RRT during the study RRT dependency at Day90 Days alive and free of RRT at Day90 Proportion of participants with eGFR decline ≥25% from reference at Day90 Change of KDIGO AKI stage from baseline at Day14.
3. Change of sequential organ failure assessment (SOFA) score from baseline to Day 30
4. Adverse events and serious adverse events

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 Town

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 23

Locations

8 EU/EEA countries · 53 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

Documents 172 files

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

Application history

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