Efficacy, Safety, Tolerability, Pharmacokinetics of Sotrastaurin-tacrolimus vs. Mycophenolic Acid-tacrolimus in de Novo Liver Transplant Patients

A 24-month Randomized Multicenter Study Evaluating Efficacy, Safety, Tolerability and Pharmacokinetics of Sotrastaurin and Tacrolimus vs. a Tacrolimus/Mycophenolate Mofetil-based Control Regimen in de Novo Liver Transplant Recipients

This study will assess the safety and efficacy of different doses of sotrastaurin when combined with tacrolimus for the prevention of acute rejection after de novo liver transplantation.

Study Overview

• Status: Completed
• Conditions: Liver Transplantation
• Intervention / Treatment: Drug: MMF(1000mg bid) + tacrolimus + standard of care medications; Drug: sotrastaurin (200mg bid) + tacrolimus + standard of care medications; Drug: sotrastaurin (300 mg bid) + tacrolimus + standard of care medications

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1181ACH
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1118AAT
      • Novartis Investigative Site
    • San Martin, Buenos Aires, Argentina, C1107BEA
      • Novartis Investigative Site
• Austria
  • Innsbruck, Austria, A-6020
    • Novartis Investigative Site
  • Wien, Austria, A-1090
    • Novartis Investigative Site
• Belgium
  • Gent, Belgium, 9000
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4G5
      • Novartis Investigative Site
• Czechia
  • Brno, Czechia, 656 91
    • Novartis Investigative Site
  • Czech Republic
    • Praha 4, Czech Republic, Czechia, 140 21
      • Novartis Investigative Site
• Finland
  • HUS, Finland, 00029
    • Novartis Investigative Site
• France
  • Bordeaux Cedex, France, 33076
    • Novartis Investigative Site
  • Chambray les Tours, France, 37044
    • Novartis Investigative Site
  • Creteil, France, 94000
    • Novartis Investigative Site
  • Paris, France, 75012
    • Novartis Investigative Site
  • Strasbourg, France, 67098
    • Novartis Investigative Site
  • Villejuif, France, 94805
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Regensburg, Germany, 93053
    • Novartis Investigative Site
• Italy
  • MI
    • Milano, MI, Italy, 20162
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35128
      • Novartis Investigative Site
  • PI
    • Pisa, PI, Italy, 56124
      • Novartis Investigative Site
• Spain
  • Andalucia
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
  • Cataluña
    • L'Hospitalet de Llobregat, Cataluña, Spain, 08907
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Novartis Investigative Site
  • Galicia
    • La Coruna, Galicia, Spain, 15006
      • Novartis Investigative Site
• Switzerland
  • Zurich, Switzerland, 8091
    • Novartis Investigative Site
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Novartis Investigative Site
    • San Francisco, California, United States, 94143
      • Novartis Investigative Site
  • Michigan
    • Detroit, Michigan, United States, 48202-2689
      • Novartis Investigative Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Novartis Investigative Site
    • Rochester, Minnesota, United States, 55905
      • Novartis Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Novartis Investigative Site
  • Texas
    • Dallas, Texas, United States, 75246
      • Novartis Investigative Site
    • Houston, Texas, United States, 77030
      • 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

Inclusion criteria:

• Recipients of any race, 18 years or older
• Recipients of primary de novo orthotopic liver transplant from a deceased donor
• Recipients of a kidney with a cold ischemia time < 30 hours
• HCV-negative recipients

Exclusion criteria:

• Prior organ/cellular transplant or multiple organ transplant
• MELD-score > 35
• HCC > Milan criteria
• Donor age < 12 years
• Cold ischemia > 15 hours
• Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) or drugs with QT-prolonging properties

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Arm 1; MMF(1000mg bid) + tacrolimus + standard of care medications	Drug: MMF(1000mg bid) + tacrolimus + standard of care medications; MMF(1000mg bid) + tacrolimus + standard of care medications
EXPERIMENTAL: Arm 2; sotrastaurin (200mg bid) + tacrolimus + standard of care medications	Drug: sotrastaurin (200mg bid) + tacrolimus + standard of care medications; sotrastaurin (200mg bid) + tacrolimus + standard of care medications
EXPERIMENTAL: Arm 3; sotrastaurin (200mg bid) + tacrolimus + standard of care medications	Drug: sotrastaurin (200mg bid) + tacrolimus + standard of care medications; sotrastaurin (200mg bid) + tacrolimus + standard of care medications
EXPERIMENTAL: Arm 4; sotrastaurin (300 mg bid) + tacrolimus + standard of care medications	Drug: sotrastaurin (300 mg bid) + tacrolimus + standard of care medications; sotrastaurin (300 mg bid) + tacrolimus + standard of care medications

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Occurrence of primary efficacy failure defined as composite efficacy endpoint (treated BPAR of Banff grade ≥ 1, graft loss, or death) in the different treatment arms.	Month 6

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluate renal allograft function post-transplantation (estimated GFR by MDRD equation; estimated creatinine clearance by Cockcroft-Gault formula; serum creatinine).	Months 3, 6, 12, and 24
Occurrence of primary efficacy failure defined as composite efficacy endpoint (treated BPAR of Banff grade ≥ 1, graft loss, or death) in the different treatment arms.	Months 12, 24
Occurrence of rejection requiring T-cell depleting antibody, occurrence of treated biopsy-proven acute rejections of Banff grade ≥ 1 that is steroid-resistant	Months 6, 12, 24
Safety and tolerability ((serious) adverse events (specifically: gastrointestinal AEs and cardiac AEs, serious infections), laboratory abnormalities, vital signs, electrocardiograms, physical examination).	Months 3, 6, 12, 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Pascher A, De Simone P, Pratschke J, Salame E, Pirenne J, Isoneimi H, Bijarnia M, Krishnan I, Klupp J. Protein kinase C inhibitor sotrastaurin in de novo liver transplant recipients: a randomized phase II trial. Am J Transplant. 2015 May;15(5):1283-92. doi: 10.1111/ajt.13175. Epub 2015 Feb 12.

Helpful Links

• Results for CAEB071B2201 from the Novartis Clinical Trials Website

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (ACTUAL): July 1, 2012
• Study Completion (ACTUAL): July 1, 2012

Study Registration Dates

• First Submitted: May 20, 2010
• First Submitted That Met QC Criteria: May 20, 2010
• First Posted (ESTIMATE): May 21, 2010

Study Record Updates

• Last Update Posted (ACTUAL): December 22, 2020
• Last Update Submitted That Met QC Criteria: December 15, 2020
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Liver transplantation; tacrolimus; deceased donor; HCV-negative recipient; sotrastaurin; oran transplantation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: CAEB071B2201; 2007-001776-36