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

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

Tracking Information

• First Submitted Date: June 4, 2018
• First Posted Date: September 10, 2018
• Last Update Posted Date: June 13, 2022
• Actual Study Start Date: November 28, 2018
• Actual Primary Completion Date: October 29, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

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

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: Interventional
• Study Phase: Phase 2

Study Design

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: Kidney Transplant Rejection

Intervention

• Biological: CFZ533 - MMF - CS
  Comparison with standard of care immunosuppression
• Drug: Tacrolimus - MMF - +/- corticosteroids
  Standard of care immunosupprevive regimen

Study Arms

• 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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 11, 2021): 418
• Original Estimated Enrollment (submitted: September 6, 2018): 325
• Actual Study Completion Date: October 29, 2021
• Actual Primary Completion Date: October 29, 2021 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: 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: NCT03663335
• Other Study ID Numbers: 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

• 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: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: June 2022