Study of Efficacy, Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) of an Anti-CD40 Monoclonal Antibody, CFZ533, in Liver Transplant Recipients With Additional 12-month Follow-up and Long-term Extension

Liver Transplant Rejection Clinical Trial

— CONTRAIL I  

Official title:

A 12-month, Open-label, Multicenter, Randomized, Safety, Efficacy, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of Two Regimens of Anti-CD40 Monoclonal Antibody, CFZ533 vs. Standard of Care Control, in Adult de Novo Liver Transplant Recipients With a 12-month Additional Follow-up and a Long-term Extension (CONTRAIL I)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03781414
• Other study ID #: CCFZ533A2202
• Secondary ID: 2018-001836-24CC
• Status: Completed
• Phase: Phase 2
• Start date: October 7, 2019
• Est. completion date: April 20, 2023

Study information

• Verified date: October 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to investigate the safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of two CFZ533 dose regimens in liver transplant recipients.

Description:

This study allowed assessment of the ability of CFZ533 to replace Calcineurin inhibitors (CNIs) in terms of anti-rejection efficacy, while providing potentially better renal function with an expected similar safety and tolerability profile. Results of this study will inform the CFZ533 dose and regimen selection for investigation in later phases of clinical development.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 129
• Est. completion date: April 20, 2023
• Est. primary completion date: April 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

Screening period up to liver transplantation: -Written informed consent obtained before any assessment.

• Male or female subjects between 18 to 70 years of age.

• Recipients of a primary liver transplant from a deceased donor.

• Up to date vaccination as per local immunization schedules.

• Recipients tested negative for HIV.

• MELD score =30.

At randomization:

• Recipients with no active HCV and HBV replication (no detectable RNA/DNA by PCR).

• Allograft is functioning at an acceptable level by the time of randomization as defined by AST, ALT, Alkaline Phosphatase levels = 5 times ULN and Total bilirubin = 2 times ULN.

• Renal function (eGFR, MDRD-4 formula) = 30 mL/min/1.73 m2 based on most recent post-transplant value prior to randomization.

Exclusion Criteria:

Screening period up to liver transplantation:

• Recipients of a liver from a donor after cardiac death (DCD), from a living donor, or of a split liver.

• A negative Epstein Barr virus (EBV) test.

• Recipients receiving an ABO incompatible allograft.

• History of malignancy of any organ system treated or untreated, within the past 5 years.

• Hepatocellular carcinoma that does not fulfill Milan criteria.

• Recipients transplanted for acute liver failure.

• Any use of antibody induction therapy, or use of any immunosuppressive medications

• Patients who have received a live vaccine within four weeks prior to transplantation.

• Recipients with donors HIV positive, HBsAg positive, HCV positive.

• Recipients with donors with hepatic steatosis > 30%.

At randomization:

• Any post-transplant history of thrombosis, occlusion or stent placement in any hepatic arteries, hepatic veins, portal vein or inferior vena cava at any time during the run-in period prior to randomization.

• Recipients with platelet count < 50,000/mm3, an absolute neutrophil count of < 1,000/mm³ or white blood cell count of < 2,000/mm³.

• Recipients with clinically significant systemic infection requiring use of intravenous (IV) antibiotics.

• Evidence of active tuberculosis (TB) infection.

• Any episode of acute rejection or suspected rejection prior to randomization.

• HCC participants whose explanted liver graft pathology report shows i) pTNM stage beyond T2N0M0, ii) presence of mixed carcinoma, iii) microvascular invasion despite pTNM stage.

• Participants with body weight < 30 kg or > 180 kg.

Related Conditions & MeSH terms

• Liver Transplant Rejection

Intervention

Biological:
• CFZ533
Comparison with standard of care immunosuppression

Drug:
• Tacrolimus - MMF - corticosteroids
Standard of care immunosupprevive regimen

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Belgium	Novartis Investigative Site	Gent
Czechia	Novartis Investigative Site	Praha 4	Czech Republic
France	Novartis Investigative Site	Chambray les Tours
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Villejuif
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Regensburg	Bavaria
Hungary	Novartis Investigative Site	Budapest
Italy	Novartis Investigative Site	Pisa	PI
Netherlands	Novartis Investigative Site	Rotterdam
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	L Hospitalet De Llobregat	Cataluna
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Sevilla	Andalucia
United States	Novartis Investigative Site	Aurora	Colorado
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Durham	North Carolina
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Czechia,  France,  Germany,  Hungary,  Italy,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with composite event (BPAR, Graft Loss or Death) over 12 months	Rate of composite efficacy failure	Baseline to Month 12
Secondary	To mean eGFR up to Month 24 post-transplantation	Renal function at Month 24 measured by Estimated Glomerular Filtration Rate (eGFR)	Baseline to month 24
Secondary	Proportion of patients with AEs and SAEs	Proportion of patients with AEs, SAEs, AEs related to study drug	Baseline to month 12 and month 24
Secondary	Proportion of patients with premature discontinuation from study and premature discontinuation of study drug	Tolerability assessment by rate of premature discontinuation from study, premature discontinuation of study drug, dose interruption and dose adjustment	Baseline to month 12 and month 24