CCFZ533X2201 - PoC Study in de Novo Renal Transplantation

A 12-month Randomized, Multiple Dose, Open-label, Study Evaluating Safety, Tolerability, Pharmacokinetics/Pharmacodynamics (PK/PD) and Efficacy of an Anti-CD40 Monoclonal Antibody, CFZ533, in Combination With Mycophenolate Mofetil (MMF) and Corticosteroids (CS), With and Without Tacrolimus (Tac), in de Novo Renal Transplant Recipients

The purpose of this study was to investigate the safety, tolerability, pharmacokinetics (PK) and potential for CFZ533 to replace calcineurin inhibitors (CNI), while providing a similar rate of acute rejection prophylaxis and renal function in a de novo renal transplant population receiving an allograft from standard criteria donors.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Biological: CFZ533; Drug: Tacrolimus (Tac); Drug: Mycophenolate mofetil (MMF); Drug: Corticosteroids (CS); Biological: anti-IL2 Induction

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Brazil
  • SP
    • São Paulo, SP, Brazil, 04038-002
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, D-13353
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Novartis Investigative Site
  • Rotterdam, Netherlands, 3000 CA
    • Novartis Investigative Site
  • The Netherlands
    • Utrecht, The Netherlands, Netherlands, 3508 GA
      • Novartis Investigative Site
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Novartis Investigative Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Novartis Investigative Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109 5271
      • Novartis Investigative Site
    • Detroit, Michigan, United States, 48202
      • Novartis Investigative Site
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Novartis Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0585
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

• Written informed consent must be obtained before any assessment is performed.
• Recipients of a kidney transplant from a heart-beating deceased, living unrelated or non-human leukocyte antigen (HLA) identical living related donor.
• Recipients of a kidney with a cold ischemia time (CIT) < 30 hours.

Main Exclusion Criteria:

• Recipients of an organ from a non-heart beating donor.
• ABO incompatible or complement-dependent lymphocytotoxic (CDC) crossmatch positive transplant.
• Subjects receiving a second kidney allograft, unless the first allograft was lost due to surgical complication.
• Subjects at high immunological risk for rejection
• Subjects at risk for tuberculosis (TB)
• Subject with severe systemic infections, current or within the two weeks prior to randomization/enrollment.
• Any additional contraindication to the use of tacrolimus or mycophenolate mofetil according to the national labeling information of these products (see local product label).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Regimen A; CFZ533 administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	Biological: CFZ533; Drug: Tacrolimus (Tac); Drug: Mycophenolate mofetil (MMF); Drug: Corticosteroids (CS)
Experimental: Regimen B; CFZ533 administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction	Biological: CFZ533; Drug: Mycophenolate mofetil (MMF); Drug: Corticosteroids (CS); Biological: anti-IL2 Induction
Active Comparator: Regimen C; Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction]	Drug: Tacrolimus (Tac); Drug: Mycophenolate mofetil (MMF); Drug: Corticosteroids (CS); Biological: anti-IL2 Induction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Cmax Pharmacokinetic Parameter- Part I	Pharmacokinetics as defined by the systemic concentrations and Cmax of certain immunosuppressant medications used in Part I	Day 1
Mean Tmax Pharmacokinetic Parameter - Part I	Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.	Day 1
Mean AUClast Pharmacokinetic Parameter - Part I	Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.	Day 1
Efficacy as Defined by the Frequency and Severity (Banff Classification) of Treated Biopsy Proven Acute Rejection (tBPAR) Adjudicated Data - Part II	To assess the activity of the investigational arm as compared to the standard of care control arm in de novo renal transplant patients as measured by the frequency and severity of tBPAR as measured on the Banff classification scale. An adjudication was performed on all on cause renal biopsies by an independent expert committee blinded to therapy.	3, 6, 9, and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1	To quantify the change from baseline and recovery of peripheral blood total soluble CD40 and total soluble CD154	Baseline to end of study (Day 1, Day 29, Day 337)
Free CD40 and Total CD40 on B Cells - Part II	The magnitude and duration of peripheral blood CD40 occupancy. MESF: molecules of equivalent soluble fluorochrome	Baseline to end of study (Day 1/predose)
Anti-CFZ533 Antibodies - Part I	To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies	Baseline to end of study
Anti-CFZ533 Antibodies - Part II	To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies	Baseline to end of study (screening, baseline, Day 141, Day 225, Day 309, Study Completion)
eGFR - Part II	Renal function as assessed by MDRD (Modification of Diet in Renal Disease) formula. eGFR: Estimated glomerular filtration rate	Day 1, Day 29, Day 337,
CFZ533 Plasma PK Concentrations - Part II	Quantify the systemic concentrations of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods. A full pharmacokinetic analysis can be performed on the concentration-time data to evaluate the impact of renal transplantation on the various medications used in the treatment regimen.	throughout study period (day 84 to day 336)
Total sCD40 Plasma Concentrations - Part II	To quantify the change from baseline and recovery of peripheral blood total soluble CD40	12 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Plain Language Trial Summary is available on novartisclinicaltrials.com

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2015
• Primary Completion (Actual): November 29, 2017
• Study Completion (Actual): November 29, 2017

Study Registration Dates

• First Submitted: August 7, 2014
• First Submitted That Met QC Criteria: August 13, 2014
• First Posted (Estimate): August 15, 2014

Study Record Updates

• Last Update Posted (Actual): September 28, 2021
• Last Update Submitted That Met QC Criteria: September 24, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: renal, de novo,
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid
• Other Study ID Numbers: CCFZ533X2201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD 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