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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 : Recruiting
First Posted : September 10, 2018
Last Update Posted : October 14, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( 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.


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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 681 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
Estimated Primary Completion Date : July 28, 2022
Estimated Study Completion Date : July 28, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1/Cohort 1
CFZ533 dose A+ MMF + Corticosteroids
Biological: CFZ533
Comparison with standard of care immunosuppression

Experimental: Arm 2/Cohort 1
CFZ533 dose B + MMF + Corticosteroids
Biological: CFZ533
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
Comparison with standard of care immunosuppression

Active Comparator: Arm 2/Cohort 2
Tac + MMF ± Corticosteroids
Drug: Tacrolimus - MMF - +/- corticosteroids
Standard of care immunosupprevive regimen




Primary Outcome Measures :
  1. Cohorts 1 and 2-mean iBox risk prediction score [ Time Frame: Month 12 ]
    Integrative score that will provide a prediction of graft survival at year 5


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

  2. 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).

  3. 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

  4. Cohorts 1 and 2-Proportion of patients wilth composite event (BPAR, Graft Loss or Death) over 12 months [ Time Frame: Baseline to month 12 ]
    Rate of composite efficacy


Other Outcome Measures:
  1. Cohort 1 and 2-Difference in kidney histopathology scores at 12 months post-transplantation [ Time Frame: Baseline to Month 12 ]
    Differences in kidney histopathology for patients on CFZ533 compared to a TAC-based regimen



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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.

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


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
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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 )
First Posted: September 10, 2018    Key Record Dates
Last Update Posted: October 14, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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