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CCFZ533X2201 - PoC Study in de Novo Renal Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02217410
Recruitment Status : Completed
First Posted : August 15, 2014
Results First Posted : December 21, 2018
Last Update Posted : September 28, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Kidney Transplantation Biological: CFZ533 Drug: Tacrolimus (Tac) Drug: Mycophenolate mofetil (MMF) Drug: Corticosteroids (CS) Biological: anti-IL2 Induction Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: 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
Actual Study Start Date : February 5, 2015
Actual Primary Completion Date : November 29, 2017
Actual Study Completion Date : November 29, 2017

Resource links provided by the National Library of Medicine


Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. Mean Cmax Pharmacokinetic Parameter- Part I [ Time Frame: Day 1 ]
    Pharmacokinetics as defined by the systemic concentrations and Cmax of certain immunosuppressant medications used in Part I

  2. Mean Tmax Pharmacokinetic Parameter - Part I [ Time Frame: Day 1 ]
    Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.

  3. Mean AUClast Pharmacokinetic Parameter - Part I [ Time Frame: Day 1 ]
    Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.

  4. Efficacy as Defined by the Frequency and Severity (Banff Classification) of Treated Biopsy Proven Acute Rejection (tBPAR) Adjudicated Data - Part II [ Time Frame: 3, 6, 9, and 12 months ]

    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.



Secondary Outcome Measures :
  1. Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 [ Time Frame: Baseline to end of study (Day 1, Day 29, Day 337) ]
    To quantify the change from baseline and recovery of peripheral blood total soluble CD40 and total soluble CD154

  2. Free CD40 and Total CD40 on B Cells - Part II [ Time Frame: Baseline to end of study (Day 1/predose) ]
    The magnitude and duration of peripheral blood CD40 occupancy. MESF: molecules of equivalent soluble fluorochrome

  3. Anti-CFZ533 Antibodies - Part I [ Time Frame: Baseline to end of study ]
    To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies

  4. Anti-CFZ533 Antibodies - Part II [ Time Frame: Baseline to end of study (screening, baseline, Day 141, Day 225, Day 309, Study Completion) ]
    To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies

  5. eGFR - Part II [ Time Frame: Day 1, Day 29, Day 337, ]

    Renal function as assessed by MDRD (Modification of Diet in Renal Disease) formula.

    eGFR: Estimated glomerular filtration rate


  6. CFZ533 Plasma PK Concentrations - Part II [ Time Frame: throughout study period (day 84 to day 336) ]
    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.

  7. Total sCD40 Plasma Concentrations - Part II [ Time Frame: 12 months ]
    To quantify the change from baseline and recovery of peripheral blood total soluble CD40


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

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).
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): NCT02217410


Locations
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United States, Colorado
Novartis Investigative Site
Aurora, Colorado, United States, 80045
United States, Maryland
Novartis Investigative Site
Baltimore, Maryland, United States, 21201
United States, Michigan
Novartis Investigative Site
Ann Arbor, Michigan, United States, 48109 5271
Novartis Investigative Site
Detroit, Michigan, United States, 48202
United States, New Jersey
Novartis Investigative Site
Livingston, New Jersey, United States, 07039
United States, Ohio
Novartis Investigative Site
Cincinnati, Ohio, United States, 45267-0585
Brazil
Novartis Investigative Site
São Paulo, SP, Brazil, 04038-002
Germany
Novartis Investigative Site
Berlin, Germany, D-13353
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Hamburg, Germany, 20246
Novartis Investigative Site
Heidelberg, Germany, 69120
Netherlands
Novartis Investigative Site
Utrecht, The Netherlands, Netherlands, 3508 GA
Novartis Investigative Site
Groningen, Netherlands, 9713 GZ
Novartis Investigative Site
Rotterdam, Netherlands, 3000 CA
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] September 20, 2017
Statistical Analysis Plan  [PDF] January 16, 2018

More Information
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Additional Information:

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02217410    
Other Study ID Numbers: CCFZ533X2201
First Posted: August 15, 2014    Key Record Dates
Results First Posted: December 21, 2018
Last Update Posted: September 28, 2021
Last Verified: September 2021
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
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
renal, de novo,
Additional relevant MeSH terms:
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Mycophenolic Acid
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
 Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents