Clinical trial NCT03663335: Study of Efficacy, Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) of an Anti-CD40 Monoclonal Antibody, CFZ533, in Kidney Transplant Recipients
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Transplant Rejection
Keywords: Renal transplantation, CFZ533, CNI-free immunosuppression, transplant rejection, allograft rejection.
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-09-10
Enrollment: 418
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study CCFZ533A2201 is a randomized, 60-month, active-controlled, partially-blinded, multicenter, dose range finding study to evaluate the efficacy, safety, tolerability, PK and PD of CFZ533 in 2 different cohorts, as compared to standard of care comprised of tacrolimus, MMF and corticosteroids.
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients with composite event (BPAR, Graft Loss or Death)
timeFrame: Month 12
Secondary outcomes:
measure: Cohorts 1 and 2-Mean eGFR over 12 months
timeFrame: Baseline to month 12
measure: Cohorts 1 and 2-Cohorts 1 and 2-safety of CFZ533 regimens compared to a tacrolimus based regimen
timeFrame: Baseline to month 12
measure: Cohorts 1 and 2-Cohorts 1 and 2 - tolerability of CFZ533 regimens compared to a tacrolimus based regimen
timeFrame: Baseline to month 12
measure: Cohorts 1 and 2-pharmacokinetics of CFZ533 during the 60 months treatment period and explore the dose-exposure relationship
timeFrame: Baseline to month 60
measure: Cohorts 1 and 2-immunogenicity of CFZ533 during the 60 months treatment period
timeFrame: Baseline to month 60
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: San Francisco
country: United States
facility: Novartis Investigative Site
state: California
city: Aurora
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Kansas City
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Baltimore
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Detroit
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Durham
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Cincinnati
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Cincinnati
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Seattle
country: United States
facility: Novartis Investigative Site
state: Washington
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Corrientes
country: Argentina
facility: Novartis Investigative Site
city: Camperdown
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Adelaide
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Clayton
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Prague 4
country: Czechia
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Grenoble
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Paris cedex 15
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex 4
country: France
facility: Novartis Investigative Site
city: Tours
country: France
facility: Novartis Investigative Site
city: Regensburg
country: Germany
facility: Novartis Investigative Site
state: Bavaria
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Nagakute-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Sapporo-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Yokohama city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kumamoto-city
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Tomigusuku
country: Japan
facility: Novartis Investigative Site
state: Okinawa
city: Suita city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
state: The Netherlands
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: L'Hospitalet de Llobregat
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Palma de Mallorca
country: Spain
facility: Novartis Investigative Site
state: Islas Baleares
city: Zaragoza
country: Spain
facility: Novartis Investigative Site
city: Göteborg
country: Sweden
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
References: