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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 )

Tracking Information
First Submitted Date  ICMJE June 4, 2018
First Posted Date  ICMJE September 10, 2018
Last Update Posted Date June 13, 2022
Actual Study Start Date  ICMJE November 28, 2018
Actual Primary Completion Date October 29, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 30, 2021)
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
Original Primary Outcome Measures  ICMJE
 (submitted: September 6, 2018)
Cohorts 1 and 2-Proportion of patients with composite event (BPAR, Graft Loss or Death) over 12 months [ Time Frame: baseline to month 12 ]
Rate of composite efficacy
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2021)
  • Cohorts 1 and 2-Mean eGFR over 12 months [ Time Frame: 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 [ 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).
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2018)
  • Cohorts 1 and 2-Mean eGFR at 12 months post-transplantation [ Time Frame: baseline to month 12 ]
    Renal function at Month 12
  • Cohorts 1 and 2-Proportion of patients with AEs and SAEs [ 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).
  • Cohorts 1 and 2-Proportion of patients with premature discontinuation from study and premature discontinuation of study drug [ 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Efficacy, Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) of an Anti-CD40 Monoclonal Antibody, CFZ533, in Kidney Transplant Recipients
Official Title  ICMJE 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)
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE Kidney Transplant Rejection
Intervention  ICMJE
  • Biological: CFZ533 - MMF - CS
    Comparison with standard of care immunosuppression
  • Drug: Tacrolimus - MMF - +/- corticosteroids
    Standard of care immunosupprevive regimen
Study Arms  ICMJE
  • Experimental: Arm 1/Cohort 1
    CFZ533 dose A+ MMF + Corticosteroids
    Intervention: Biological: CFZ533 - MMF - CS
  • Experimental: Arm 2/Cohort 1
    CFZ533 dose B + MMF + Corticosteroids
    Intervention: Biological: CFZ533 - MMF - CS
  • Active Comparator: Arm 3/Cohort 1
    Control/Standard of Care: TAC + MMF + Corticosteroids
    Intervention: Drug: Tacrolimus - MMF - +/- corticosteroids
  • Experimental: Arm 1/Cohort 2
    CFZ533 dose C + MMF ± Corticosteroids
    Intervention: Biological: CFZ533 - MMF - CS
  • Active Comparator: Arm 2/Cohort 2
    Tac + MMF ± Corticosteroids
    Intervention: Drug: Tacrolimus - MMF - +/- corticosteroids
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 11, 2021)
418
Original Estimated Enrollment  ICMJE
 (submitted: September 6, 2018)
325
Actual Study Completion Date  ICMJE October 29, 2021
Actual Primary Completion Date October 29, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Canada,   Czechia,   France,   Germany,   Hungary,   Italy,   Japan,   Korea, Republic of,   Latvia,   Netherlands,   Norway,   Spain,   Sweden,   Switzerland,   United Kingdom,   United States
Removed Location Countries Estonia,   Lithuania,   Slovakia
 
Administrative Information
NCT Number  ICMJE NCT03663335
Other Study ID Numbers  ICMJE CCFZ533A2201
2017-003607-22 ( EudraCT Number )
CCFZ533A2201 ( Other Identifier: Novartis )
03663335 ( Other Identifier: Clinicaltrials.gov )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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

Current Responsible Party Novartis ( Novartis Pharmaceuticals )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Novartis Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date June 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP