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

Novartis

Status and phase: Completed; Phase 2

Conditions: Kidney Transplant Rejection

Treatments: Drug: Tacrolimus - MMF - +/- corticosteroids; Biological: CFZ533 - MMF - CS

Study type: Interventional

Funder types: Industry

Identifiers

NCT03663335

03663335 (Other Identifier)

2017-003607-22 (EudraCT Number)

CCFZ533A2201 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 418 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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418 participants in 5 patient groups

Arm 1/Cohort 1

Experimental group

Description:

CFZ533 dose A+ MMF + Corticosteroids

Treatment:

Biological: CFZ533 - MMF - CS

Arm 2/Cohort 1

Experimental group

Description:

CFZ533 dose B + MMF + Corticosteroids

Treatment:

Biological: CFZ533 - MMF - CS

Arm 3/Cohort 1

Active Comparator group

Description:

Control/Standard of Care: TAC + MMF + Corticosteroids

Treatment:

Drug: Tacrolimus - MMF - +/- corticosteroids

Arm 1/Cohort 2

Experimental group

Description:

CFZ533 dose C + MMF ± Corticosteroids

Treatment:

Biological: CFZ533 - MMF - CS

Arm 2/Cohort 2

Active Comparator group

Description:

Tac + MMF ± Corticosteroids

Treatment:

Drug: Tacrolimus - MMF - +/- corticosteroids