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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 With Additional 12-month Follow-up and Long-term Extension (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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03781414
Recruitment Status : Active, not recruiting
First Posted : December 19, 2018
Last Update Posted : January 18, 2023
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)
Actual Enrollment : 131 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 Two Regimens of Anti-CD40 Monoclonal Antibody, CFZ533 vs. Standard of Care Control, in Adult de Novo Liver Transplant Recipients With a 12-month Additional Follow-up and a Long-term Extension (CONTRAIL I)
Actual Study Start Date : October 7, 2019
Estimated Primary Completion Date : October 19, 2026
Estimated Study Completion Date : October 19, 2026

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. To mean eGFR up to Month 24 post-transplantation [ Time Frame: Baseline to month 24 ]
    Renal function at Month 24 measured by Estimated Glomerular Filtration Rate (eGFR)

  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

  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

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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, Alkaline Phosphatase levels ≤ 5 times ULN and Total bilirubin ≤ 2 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.
  • 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.
  • HCC participants whose explanted liver graft pathology report shows i) pTNM stage beyond T2N0M0, ii) presence of mixed carcinoma, iii) microvascular invasion despite pTNM stage.
  • Participants with body weight &lt; 30 kg or &gt; 180 kg.

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): NCT03781414

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United States, California
Novartis Investigative Site
Los Angeles, California, United States, 90033
United States, Colorado
Novartis Investigative Site
Aurora, Colorado, United States, 80045
United States, Illinois
Novartis Investigative Site
Chicago, Illinois, United States, 60611
United States, Michigan
Novartis Investigative Site
Detroit, Michigan, United States, 48202
United States, Missouri
Novartis Investigative Site
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Novartis Investigative Site
Durham, North Carolina, United States, 27710
United States, Ohio
Novartis Investigative Site
Cincinnati, Ohio, United States, 45267
United States, South Carolina
Novartis Investigative Site
Charleston, South Carolina, United States, 29425
United States, Texas
Novartis Investigative Site
Houston, Texas, United States, 77030
Novartis Investigative Site
Caba, Buenos Aires, Argentina, C1118AAT
Novartis Investigative Site
Caba, Buenos Aires, Argentina, C1181ACH
Novartis Investigative Site
Caba, Buenos Aires, Argentina, C1280AEB
Novartis Investigative Site
Gent, Belgium, 9000
Novartis Investigative Site
Praha 4, Czech Republic, Czechia, 140 21
Novartis Investigative Site
Chambray les Tours, France, 37044
Novartis Investigative Site
Lille Cedex, France, 59 037
Novartis Investigative Site
Montpellier, France, 34295
Novartis Investigative Site
Villejuif, France, 94805
Novartis Investigative Site
Regensburg, Bavaria, Germany, 93053
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Hamburg, Germany, 20246
Novartis Investigative Site
Muenster, Germany, 48149
Novartis Investigative Site
Budapest, Hungary, 1085
Novartis Investigative Site
Pisa, PI, Italy, 56124
Novartis Investigative Site
Rotterdam, Netherlands, 3015 CE
Novartis Investigative Site
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site
L Hospitalet De Llobregat, Cataluna, Spain, 08907
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site
Madrid, Spain, 28009
Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03781414    
Other Study ID Numbers: CCFZ533A2202
2018-001836-24 ( EudraCT Number )
CCFZ533A2202 ( Other Identifier: Novartis )
First Posted: December 19, 2018    Key Record Dates
Last Update Posted: January 18, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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 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 ):
Liver transplantation
de novo recipients
deceased donor
CNI-free immunosuppression
Transplant rejection
Additional relevant MeSH terms:
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Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action