Study of Efficacy, Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) of an Anti-CD40 Monoclonal Antibody, CFZ533, in Kidney Transplant Recipients

Kidney Transplant Rejection Clinical Trial

— CIRRUS I  

Official title:

A Partially-blinded, Active-controlled, Multicenter, Randomized Study Evaluating Efficacy, Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) of an Anti-CD40 Monoclonal Antibody, CFZ533, in de Novo and Maintenance Kidney Transplant Recipients (CIRRUS I)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03663335
• Other study ID #: CCFZ533A2201
• Secondary ID: 2017-003607-22CC
• Status: Completed
• Phase: Phase 2
• Start date: November 28, 2018
• Est. completion date: October 29, 2021

Study information

• Verified date: June 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 418
• Est. completion date: October 29, 2021
• Est. primary completion date: October 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent obtained before any assessment.

• Male or female patient = 18 years old.

• Up to date vaccination as per local immunization schedules.

• Recipients of a kidney transplant

• Recipients of a primary kidney transplant from a heart-beating deceased, living unrelated or non-HLA identical living related donors.

Exclusion Criteria:

• Multi-organ transplant recipients or prior kidney transplant.

• Recipients of an organ from a non-heart beating donor.

• Recipient of an organ from an HLA identical living related donor.

• ABO incompatible or complement-dependent lymphocytotoxic (CDC) crossmatch positive transplant

• Recipients of kidneys from donors who are older than 65 years.

• Recipients of kidneys from donors with terminal serum creatinine > 2 mg/dL.

• Patients at high immunological risk for rejection

• Patient who is anti-HIV positive, HBsAg-positive or anti-HCV positive (without proof of sustained viral response (SVR) after anti-HCV treatment).

• Recipient of a kidney from a donor who tests positive for HIV, HBsAg/HBc positive or HCV.

• A negative Epstein Barr virus (EBV) test.

• Evidence of advanced liver disease (Child-Pugh C), or any sign of liver decompensation.

• Patient with severe systemic infections, current or within the two weeks prior to randomization.

• History of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases, with the exception of localized excised non-melanomatous skin lesions.

Related Conditions & MeSH terms

• Kidney Transplant Rejection

Intervention

Biological:
• CFZ533 - MMF - CS
Comparison with standard of care immunosuppression

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

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Corrientes
Australia	Novartis Investigative Site	Adelaide	South Australia
Australia	Novartis Investigative Site	Camperdown	New South Wales
Australia	Novartis Investigative Site	Clayton	Victoria
Belgium	Novartis Investigative Site	Leuven
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	São Paulo	SP
Canada	Novartis Investigative Site	Vancouver	British Columbia
Czechia	Novartis Investigative Site	Prague 4
France	Novartis Investigative Site	Bordeaux Cedex
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Grenoble
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Paris cedex 15
France	Novartis Investigative Site	Toulouse Cedex 4
France	Novartis Investigative Site	Tours
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Regensburg	Bavaria
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Roma	RM
Japan	Novartis Investigative Site	Kumamoto-city	Kumamoto
Japan	Novartis Investigative Site	Nagakute-city	Aichi
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Sapporo city	Hokkaido
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Suita city	Osaka
Japan	Novartis Investigative Site	Tomigusuku	Okinawa
Japan	Novartis Investigative Site	Yokohama city	Kanagawa
Korea, Republic of	Novartis Investigative Site	Seoul
Latvia	Novartis Investigative Site	Riga
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Utrecht	The Netherlands
Norway	Novartis Investigative Site	Oslo
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	L'Hospitalet de Llobregat	Cataluña
Spain	Novartis Investigative Site	Palma de Mallorca	Islas Baleares
Spain	Novartis Investigative Site	Zaragoza
Sweden	Novartis Investigative Site	Göteborg
Sweden	Novartis Investigative Site	Uppsala
Switzerland	Novartis Investigative Site	Bern
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester
United States	Novartis Investigative Site	Aurora	Colorado
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Durham	North Carolina
United States	Novartis Investigative Site	Kansas City	Kansas
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	San Francisco	California
United States	Novartis Investigative Site	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Czechia,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Latvia,  Netherlands,  Norway,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with composite event (BPAR, Graft Loss or Death)	Cohorts 1 and 2-Proportion of patients with composite event (BPAR, Graft Loss or Death) over 12 months	Month 12
Secondary	Cohorts 1 and 2-Mean eGFR over 12 months	Renal function at Month 12	Baseline to month 12
Secondary	Cohorts 1 and 2-Cohorts 1 and 2-safety of CFZ533 regimens compared to a tacrolimus based regimen	Proportion of patients with AEs, SAEs, infections, malignancies, thromboembolic events, major adverse cardiovascular events, new onset diabetes mellitus (NODM).	Baseline to month 12
Secondary	Cohorts 1 and 2-Cohorts 1 and 2 - tolerability of CFZ533 regimens compared to a tacrolimus based regimen	Tolerability assessment by rate of premature discontinuation from study, premature discontinuation of study drug, dose interruption and dose adjustment	Baseline to month 12
Secondary	Cohorts 1 and 2-pharmacokinetics of CFZ533 during the 60 months treatment period and explore the dose-exposure relationship	Free CFZ533 plasma concentrations over time	Baseline to month 60
Secondary	Cohorts 1 and 2-immunogenicity of CFZ533 during the 60 months treatment period	Semi-quantitative analysis of anti-CFZ533 antibodies in plasma	Baseline to month 60