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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03781414
Recruitment Status : Not yet recruiting
First Posted : December 19, 2018
Last Update Posted : December 19, 2018
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 two CFZ533 dose regimens in liver transplant recipients.

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

Detailed Description:
This study will allow assessment of the ability of CFZ533 to replace Calcineurin inhibitors (CNIs) in terms of anti-rejection efficacy, while providing potentially better renal function with an expected similar 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 128 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Study CCFZ533A2202 is a randomized, 12-month, active-controlled, multicenter, dose range finding study to evaluate the efficacy, safety, tolerability, PK and PD of CFZ533, as compared to standard of care comprised of tacrolimus, MMF and corticosteroids, with a 12-month additional follow up.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 12-month, Open-label, Multicenter, Randomized, Safety, Efficacy, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of an Anti-CD40 Monoclonal Antibody, CFZ533 vs. Standard of Care Control, in Adult de Novo Liver Transplant Recipients With a 12-month Additional Follow-up (CONTRAIL I)
Estimated Study Start Date : June 25, 2019
Estimated Primary Completion Date : September 24, 2021
Estimated Study Completion Date : September 24, 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Arm 1
Control/Standard of Care: TAC + MMF + Corticosteroids
Drug: Tacrolimus - MMF - corticosteroids
Standard of care immunosupprevive regimen

Experimental: Arm 2
CFZ533 dose A + MMF + Corticosteroids
Biological: CFZ533
Comparison with standard of care immunosuppression

Experimental: Arm 3
CFZ533 dose B + MMF + Corticosteroids
Biological: CFZ533
Comparison with standard of care immunosuppression

Primary Outcome Measures :
  1. Proportion of patients with composite event (BPAR, Graft Loss or Death) over 12 months [ Time Frame: Baseline to Month 12 ]
    Rate of composite efficacy failure

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

  2. Proportion of patients with AEs and SAEs [ Time Frame: Baseline to month 12 and month 24 ]
    Proportion of patients with AEs, SAEs, AEs related to study drug, AEs of special interest

  3. Proportion of patients with premature discontinuation from study and premature discontinuation of study drug [ Time Frame: Baseline to month 12 and month 24 ]
    Tolerability assessment by rate of premature discontinuation from study, premature discontinuation of study drug, dose interruption and dose adjustment

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 to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Screening period up to liver transplantation: -Written informed consent obtained before any assessment.

  • Male or female subjects between 18 to 70 years of age.
  • Recipients of a primary liver transplant from a deceased donor.
  • Up to date vaccination as per local immunization schedules.
  • Recipients tested negative for HIV.
  • MELD score ≤30.

At randomization:

  • Recipients with no active HCV and HBV replication (no detectable RNA/DNA by PCR).
  • Allograft is functioning at an acceptable level by the time of randomization as defined by AST, ALT, Total Bilirubin, and Alkaline Phosphatase levels ≤ 5 times ULN.
  • Renal function (eGFR, MDRD-4 formula) ≥ 30 mL/min/1.73 m2 based on most recent post-transplant value prior to randomization.

Exclusion Criteria:

Screening period up to liver transplantation:

  • Recipients of a liver from a donor after cardiac death (DCD), from a living donor, or of a split liver.
  • Recipients who have tested positive for HIV.
  • A negative Epstein Barr virus (EBV) test.
  • Recipients receiving an ABO incompatible allograft.
  • History of malignancy of any organ system treated or untreated, within the past 5 years.
  • Hepatocellular carcinoma that does not fulfill Milan criteria.
  • Recipients transplanted for acute liver failure.
  • Any use of antibody induction therapy, or use of any immunosuppressive medications
  • Patients who have received a live vaccine within four weeks prior to transplantation.
  • Recipients with donors HIV positive, HBsAg positive, HCV positive.
  • Recipients with donors with hepatic steatosis > 30%.

At randomization:

  • Any post-transplant history of thrombosis, occlusion or stent placement in any hepatic arteries, hepatic veins, portal vein or inferior vena cava at any time during the run-in period prior to randomization.
  • Recipients with platelet count < 50,000/mm3, an absolute neutrophil count of < 1,000/mm³ or white blood cell count of < 2,000/mm³.
  • Recipients with clinically significant systemic infection requiring use of intravenous (IV) antibiotics.
  • Evidence of active tuberculosis (TB) infection.
  • Any episode of acute rejection or suspected rejection prior to randomization.

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 identifier (NCT number): NCT03781414

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Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

Sponsors and Collaborators
Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals Identifier: NCT03781414     History of Changes
Other Study ID Numbers: CCFZ533A2202
First Posted: December 19, 2018    Key Record Dates
Last Update Posted: December 19, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect 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

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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 ):
Liver transplantation
de novo recipients
deceased donor
CNI-free immunosuppression
Transplant rejection

Additional relevant MeSH terms:
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Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Antineoplastic Agents