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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 (CONTRAIL I)

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ClinicalTrials.gov Identifier: NCT03781414
Recruitment Status : Recruiting
First Posted : December 19, 2018
Last Update Posted : December 1, 2020
Sponsor:
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)
Actual Study Start Date : October 7, 2019
Estimated Primary Completion Date : May 31, 2022
Estimated Study Completion Date : April 26, 2023

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



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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
Criteria

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.
  • 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 ClinicalTrials.gov identifier (NCT number): NCT03781414


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, California
Novartis Investigative Site Recruiting
Los Angeles, California, United States, 90033
Novartis Investigative Site Recruiting
San Francisco, California, United States, 94143
United States, Colorado
Novartis Investigative Site Recruiting
Aurora, Colorado, United States, 80045
United States, Illinois
Novartis Investigative Site Recruiting
Chicago, Illinois, United States, 60611
United States, Massachusetts
Novartis Investigative Site Recruiting
Boston, Massachusetts, United States, 02114
United States, Michigan
Novartis Investigative Site Recruiting
Detroit, Michigan, United States, 48202
United States, Missouri
Novartis Investigative Site Recruiting
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Novartis Investigative Site Recruiting
Durham, North Carolina, United States, 27710
United States, Ohio
Novartis Investigative Site Recruiting
Cincinnati, Ohio, United States, 45267
United States, South Carolina
Novartis Investigative Site Recruiting
Charleston, South Carolina, United States, 29425
United States, Texas
Novartis Investigative Site Recruiting
Dallas, Texas, United States, 75246
Novartis Investigative Site Recruiting
Houston, Texas, United States, 77030
United States, Washington
Novartis Investigative Site Recruiting
Seattle, Washington, United States, 98195
Belgium
Novartis Investigative Site Recruiting
Bruxelles, Belgium, 1070
Novartis Investigative Site Recruiting
Gent, Belgium, 9000
Novartis Investigative Site Recruiting
Leuven, Belgium, 3000
Czechia
Novartis Investigative Site Recruiting
Praha 4, Czech Republic, Czechia, 140 21
France
Novartis Investigative Site Recruiting
Chambray les Tours, France, 37044
Novartis Investigative Site Recruiting
Lille Cedex, France, 59 037
Novartis Investigative Site Recruiting
Montpellier, France, 34295
Novartis Investigative Site Recruiting
Paris Cedex 13, France, 75651
Novartis Investigative Site Recruiting
Rennes, France, 35043
Novartis Investigative Site Recruiting
Villejuif, France, 94805
Germany
Novartis Investigative Site Recruiting
Regensburg, Bavaria, Germany, 93053
Novartis Investigative Site Recruiting
Berlin, Germany, 13353
Novartis Investigative Site Recruiting
Hamburg, Germany, 20246
Novartis Investigative Site Recruiting
Kiel, Germany, 24105
Novartis Investigative Site Recruiting
Leipzig, Germany, 04103
Novartis Investigative Site Recruiting
Muenster, Germany, 48149
Novartis Investigative Site Recruiting
Tübingen, Germany, 72076
Hungary
Novartis Investigative Site Recruiting
Budapest, Hungary, 1082
Italy
Novartis Investigative Site Recruiting
Bergamo, BG, Italy, 24128
Novartis Investigative Site Recruiting
Pisa, PI, Italy, 56124
Netherlands
Novartis Investigative Site Recruiting
Rotterdam, Netherlands, 3015 CE
Spain
Novartis Investigative Site Recruiting
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site Recruiting
Valladolid, Castilla Y Leon, Spain, 47012
Novartis Investigative Site Recruiting
L Hospitalet De Llobregat, Cataluna, Spain, 08907
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site Recruiting
Baracaldo, Vizcaya, Spain, 48903
United Kingdom
Novartis Investigative Site Recruiting
London, United Kingdom, SE5 9RS
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: December 1, 2020
Last Verified: November 2020
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 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
CFZ533
CNI-free immunosuppression
Transplant rejection
Additional relevant MeSH terms:
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Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action