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

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ClinicalTrials.gov Identifier: NCT03663335
Recruitment Status : Completed
First Posted : September 10, 2018
Last Update Posted : June 13, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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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.


Condition or disease Intervention/treatment Phase
Kidney Transplant Rejection Biological: CFZ533 - MMF - CS Drug: Tacrolimus - MMF - +/- corticosteroids Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 418 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : November 28, 2018
Actual Primary Completion Date : October 29, 2021
Actual Study Completion Date : October 29, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm 1/Cohort 1
CFZ533 dose A+ MMF + Corticosteroids
 Biological: CFZ533 - MMF - CS
Comparison with standard of care immunosuppression
Experimental: Arm 2/Cohort 1
CFZ533 dose B + MMF + Corticosteroids
 Biological: CFZ533 - MMF - CS
Comparison with standard of care immunosuppression
Active Comparator: Arm 3/Cohort 1
Control/Standard of Care: TAC + MMF + Corticosteroids
 Drug: Tacrolimus - MMF - +/- corticosteroids
Standard of care immunosupprevive regimen
Experimental: Arm 1/Cohort 2
CFZ533 dose C + MMF ± Corticosteroids
 Biological: CFZ533 - MMF - CS
Comparison with standard of care immunosuppression
Active Comparator: Arm 2/Cohort 2
Tac + MMF ± Corticosteroids
 Drug: Tacrolimus - MMF - +/- corticosteroids
Standard of care immunosupprevive regimen


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of patients with composite event (BPAR, Graft Loss or Death) [ Time Frame: Month 12 ]
    Cohorts 1 and 2-Proportion of patients with composite event (BPAR, Graft Loss or Death) over 12 months


Secondary Outcome Measures :
  1. Cohorts 1 and 2-Mean eGFR over 12 months [ Time Frame: Baseline to month 12 ]
    Renal function at Month 12

  2. Cohorts 1 and 2-Cohorts 1 and 2-safety of CFZ533 regimens compared to a tacrolimus based regimen [ Time Frame: Baseline to month 12 ]
    Proportion of patients with AEs, SAEs, infections, malignancies, thromboembolic events, major adverse cardiovascular events, new onset diabetes mellitus (NODM).

  3. Cohorts 1 and 2-Cohorts 1 and 2 - tolerability of CFZ533 regimens compared to a tacrolimus based regimen [ Time Frame: Baseline to month 12 ]
    Tolerability assessment by rate of premature discontinuation from study, premature discontinuation of study drug, dose interruption and dose adjustment

  4. Cohorts 1 and 2-pharmacokinetics of CFZ533 during the 60 months treatment period and explore the dose-exposure relationship [ Time Frame: Baseline to month 60 ]
    Free CFZ533 plasma concentrations over time

  5. Cohorts 1 and 2-immunogenicity of CFZ533 during the 60 months treatment period [ Time Frame: Baseline to month 60 ]
    Semi-quantitative analysis of anti-CFZ533 antibodies in plasma


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03663335


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03663335    
Other Study ID Numbers: CCFZ533A2201
2017-003607-22 ( EudraCT Number )
CCFZ533A2201 ( Other Identifier: Novartis )
03663335 ( Other Identifier: Clinicaltrials.gov )
First Posted: September 10, 2018    Key Record Dates
Last Update Posted: June 13, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Renal transplantation, CFZ533, CNI-free immunosuppression, transplant rejection, allograft rejection.
Additional relevant MeSH terms:
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Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
 Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action