Safety and Efficacy of Basiliximab, Delayed Dose Tacrolimus Plus ECMPA (Enteric Coated Mycophenolic Acid) Following Liver Transplantation

NCT02123108 | Completed Phase 4 Results

• 1 other identifier: UCLA: CCHI621AUS17T
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator initiated study at the University of California, Los Angeles (UCLA) funded by Novartis looking at using a combination of immunosuppressive drugs in liver transplant patients that are at risk of developing kidney problems. Kidney problems following liver transplants is the most problematic issue facing liver transplant patients today. This study will generate information in this area of high unmet medical need utilizing basiliximab and Myfortic and using a reduced dose of tacrolimus, one of the current standard of care medications, after kidney function has normalized.

Conditions

Liver Transplantation

Keywords

Simulect; Myfortic; Orthotopic liver transplantation (OLT); Renal Dysfunction

Outcome Measures

Primary Outcomes (1)

• Renal Recovery/ Function

  Number of participants who experienced dialysis independence or improvement based upon kidney function labs as a measure of renal recovery/ function following OLT in patients after undergoing orthotopic liver transplant

  12 months post-transplant

Other Outcomes (4)

• Participants Experiencing Adverse Event Attributable to Study Drug

  12 months post liver transplantation

• Participants Experiencing Acute Rejection Episode

  12 months post liver transplant

• Survival

  12 months post liver transplant

Study Arms (2)

Basiliximab

EXPERIMENTAL

Tacrolimus with Basiliximab induction

Drug: Basiliximab; Drug: Tacrolimus; Drug: Mycophenolic Acid

Tacrolimus Group

ACTIVE COMPARATOR

Tacrolimus (without basiliximab induction); standard of care group

Drug: Tacrolimus; Drug: Mycophenolic Acid

Interventions

Basiliximab DRUG

Peri-operative 40 mg IV dose within 4 hours of OLT Postoperative 20mg IV dose Day 4

Also known as: Simulect

Basiliximab

Tacrolimus DRUG

Day #7 post-transplant or when serum creatinine (SCr) \< 1.8 mg/dl 6 months to 1 year: 0.03-0.1 mg.kg q12h po to maintain whole blood trough concentration of 3-5ng/mL

Also known as: Prograf

Basiliximab

Mycophenolic Acid DRUG

Enteric coated mycophenolic acid 360-720 mg po bid

Also known as: Myfortic, Mycophenolate sodium

Basiliximab; Tacrolimus Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>18 years old
• Undergoing first or second OLT
• MELD (model for end-stage liver disease) score \>25
• Serum creatinine \> 1.5 or ongoing hemodialysis for less than 4 weeks at the time of transplant
• Able and agreeable to conform to requirements of the study
• Patients or proxy must give written informed consent before any assessment is performed.

You may not qualify if:

• \<18 years old
• Serum creatinine \<1.5
• MELD Score \< 25
• Ongoing hemodialysis for 4 or more weeks (those patients become eligible for renal transplants at that point per UCLA practice).
• Receiving OKT3 (Muromonab-CD3), ATG (Antithymocyte Globulin), or IVIG (Intravenous Immunoglobulin Therapy) therapy around time of transplant
• Participating in another clinical research study involving the evaluation of another investigational drug or device
• Prior documented allergy to any of the study medications
• Active Fungal infection

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Novartis: collaborator

Study Sites (1)

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Related Publications (10)

• Ramirez CB, Marino IR. The role of basiliximab induction therapy in organ transplantation. Expert Opin Biol Ther. 2007 Jan;7(1):137-48. doi: 10.1517/14712598.7.1.137.

  PMID: 17150025 BACKGROUND

• Katari SR, Magnone M, Shapiro R, Jordan M, Scantlebury V, Vivas C, Gritsch A, McCauley J, Starzl T, Demetris AJ, Randhawa PS. Clinical features of acute reversible tacrolimus (FK 506) nephrotoxicity in kidney transplant recipients. Clin Transplant. 1997 Jun;11(3):237-42.

  PMID: 9193849 BACKGROUND

• Rimola A, Gavaler JS, Schade RR, el-Lankany S, Starzl TE, Van Thiel DH. Effects of renal impairment on liver transplantation. Gastroenterology. 1987 Jul;93(1):148-56. doi: 10.1016/0016-5085(87)90327-1.

  PMID: 3556303 BACKGROUND

• Klintmalm GB, Gonwa TA. Nephrotoxicity associated with cyclosporine and FK506. Liver Transpl Surg. 1995 Sep;1(5 Suppl 1):11-9.

  PMID: 9346596 BACKGROUND

• Guckelberger O, Bechstein WO, Neuhaus R, Luesebrink R, Lemmens HP, Kratschmer B, Jonas S, Neuhaus PL. Cardiovascular risk factors in long-term follow-up after orthotopic liver transplantation. Clin Transplant. 1997 Feb;11(1):60-5.

  PMID: 9067697 BACKGROUND

• Neuhaus P, Clavien PA, Kittur D, Salizzoni M, Rimola A, Abeywickrama K, Ortmann E, Chodoff L, Hall M, Korn A, Nashan B; CHIC 304 International Liver Study Group. Improved treatment response with basiliximab immunoprophylaxis after liver transplantation: results from a double-blind randomized placebo-controlled trial. Liver Transpl. 2002 Feb;8(2):132-42. doi: 10.1053/jlts.2002.30302.

  PMID: 11862589 BACKGROUND

• Calmus Y, Scheele JR, Gonzalez-Pinto I, Jaurrieta EJ, Klar E, Pageaux GP, Scudamore CH, Cuervas-Mons V, Metselaar HJ, Prestele H, Girault D. Immunoprophylaxis with basiliximab, a chimeric anti-interleukin-2 receptor monoclonal antibody, in combination with azathioprine-containing triple therapy in liver transplant recipients. Liver Transpl. 2002 Feb;8(2):123-31. doi: 10.1053/jlts.2002.30882.

  PMID: 11862588 BACKGROUND

• Onrust SV, Wiseman LR. Basiliximab. Drugs. 1999 Feb;57(2):207-13; discussion 214. doi: 10.2165/00003495-199957020-00006.

  PMID: 10188761 BACKGROUND

• Cherqui D, Duvoux C, Charlotte F, Humeres R, Lauzet JY, Metreau JM, Salvat A, Rotman N, Julien M, Fagniez PL, et al. [Value of a powerful initial immunosuppression after liver transplantation. Prospective study of 60 cases]. Gastroenterol Clin Biol. 1994;18(2):115-22. French.

  PMID: 8013792 BACKGROUND

• Berard JL, Velez RL, Freeman RB, Tsunoda SM. A review of interleukin-2 receptor antagonists in solid organ transplantation. Pharmacotherapy. 1999 Oct;19(10):1127-37. doi: 10.1592/phco.19.15.1127.30582.

  PMID: 10512062 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Basiliximab; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Dr. Fady M. Kaldas
• Organization: University of California Los Angeles

FKaldas@mednet.ucla.edu

310-825-8138

Study Officials

• Fady M Kaldas, MD

  UCLA Department of Surgery

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle-Investigator

Study Record Dates

• First Submitted: February 24, 2014
• First Posted: April 25, 2014
• Study Start: January 1, 2011
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: September 29, 2022
• Results First Posted: September 29, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)