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

Phase 2

Completed

• Conditions: Kidney Transplant Rejection
• Interventions: Drug: Tacrolimus - MMF - +/- corticosteroids; Biological: CFZ533 - MMF - CS

• Registration Number: NCT03663335
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-06-04
• Study First Submitted QC: 2018-09-06
• Study First Posted: 2018-09-10
• Study Start: 2018-11-28
• Primary Completion: 2021-10-29
• Study Completion: 2021-10-29
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-08
• Last Update Posted: 2022-06-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 418

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 2/Cohort 2	Tacrolimus - MMF - +/- corticosteroids	Tac + MMF ± Corticosteroids
Arm 2/Cohort 1	CFZ533 - MMF - CS	CFZ533 dose B + MMF + Corticosteroids
Arm 3/Cohort 1	Tacrolimus - MMF - +/- corticosteroids	Control/Standard of Care: TAC + MMF + Corticosteroids
Arm 1/Cohort 1	CFZ533 - MMF - CS	CFZ533 dose A+ MMF + Corticosteroids
Arm 1/Cohort 2	CFZ533 - MMF - CS	CFZ533 dose C + MMF ± Corticosteroids

Primary Outcome Measures

Name	Time	Method
Proportion of patients with composite event (BPAR, Graft Loss or Death)	Month 12	Cohorts 1 and 2-Proportion of patients with composite event (BPAR, Graft Loss or Death) over 12 months

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 Manchester, United Kingdom