Mycophenolic Acid (MPA) Monotherapy in Liver Transplantation

NCT01230502 | Terminated Results DMC

• 2 other identifiers: UW H-2010-0121CERL080AUS80T
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

To determine whether long-term maintenance therapy with a single drug (Myfortic) applied using advanced immunologic monitoring tools in selected patients can lead to superior native kidney function at 2 years without resulting in increased acute rejection episodes or deterioration of liver allograft function.

Conditions

Liver Transplant

Keywords

immunosuppression; anti-rejection; immune tolerance

Outcome Measures

Primary Outcomes (2)

• Modification of Diet in Renal Disease (MDRD) Estimation of Glomerular Filtration Rate (GFR)

  This outcome measure is used to determine if the reduction of calcineurin inhibitor immunosuppression leads to improved native kidney function. Native kidney function is assessed using the Modification of Diet in Renal Disease (MDRD) estimation of glomerular filtration rate (GFR) from serum or plasma creatinine samples at the reported time points. Reference intervals include: Healthy 18 years and up: 60-120 mL/min/1.73 sqm Chronic kidney disease: GFR \< 60 mL/min/1.73 sqm Kidney failure: GFR \< 15 mL/min/1.73 sqm

  6 months post enrollment/randomization

• Modification of Diet in Renal Disease (MDRD) Estimation of Glomerular Filtration Rate (GFR)

  This outcome measure is used to determine if the reduction of calcineurin inhibitor immunosuppression leads to improved native kidney function. Native kidney function is assessed using the Modification of Diet in Renal Disease (MDRD) estimation of glomerular filtration rate (GFR) from serum or plasma creatinine samples at the reported time points. Reference intervals include: Healthy 18 years and up: 60-120 mL/min/1.73 sqm Chronic kidney disease: GFR \< 60 mL/min/1.73 sqm Kidney failure: GFR \< 15 mL/min/1.73 sqm

  12 months post enrollment/randomization

Study Arms (3)

Group 3: Donor Specific Regulation (DSR) -, standard of care

ACTIVE COMPARATOR

Subjects who test Donor Specific Regulation (DSR) negative will not be randomized to possible tacrolimus withdrawal, and will remain on standard of care immunosuppression.

Other: data and sample collection

Group 2 Donor Specific Regulation (DSR) +; standard of care

ACTIVE COMPARATOR

Subjects that are Donor Specific Regulation (DSR) positive and randomized (1:1) to Group 2 will remain on standard of care immunosuppression.

Other: data and sample collection

Group 1 Donor Specific Regulation (DSR) +, MPA monotherapy

EXPERIMENTAL

Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapy: Subjects that are Donor Specific Regulation (DSR) positive and randomized (1:1) to Group 1 will begin a taper off tacrolimus for 6 months, after repeat DSR testing at 6 months subject will either discontinue tacrolimus if they remain DSR negative or remain at reduced dose if converted to DSR positive

Drug: Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapy

Interventions

Group 1 Donor Specific Regulation (DSR) +, Mycophenolic acid (MPA) monotherapy DRUG

Group 1 Donor Specific Regulation (DSR) +, MPA monotherapy Mycophenolate sodium : Myfortic therapy will be maintained at a target dose of 720mg BID. Tacrolimus doses will be lowered to achieve levels of 3-5 ng/ml. 6 months later, immunological monitoring will be repeated and tacrolimus will be completely discontinued if the subject remains DSR + without development of donor specific antibodies (DSA). Those who become DSR- or develop DSA will remain on a tacrolimus dose achieving levels of 3-5 ng/ml, and will not undergone any additional reduction. Subjects will be followed for 24 months at 6 month intervals, and will provide health information and blood samples.

Also known as: Myfortic

Group 1 Donor Specific Regulation (DSR) +, MPA monotherapy

data and sample collection OTHER

Group 2 : Donor specific regulation (DSR) + standard of care: These subjects will be maintained on standard of care immunosuppression consisting of Tacrolimus and Mycophenolate sodium (MPS) with no reduction in tacrolimus dose during the 24 months of study enrollment. Subjects will be followed for 24 months at 6 month intervals, and will provide health information and blood samples

Group 2 Donor Specific Regulation (DSR) +; standard of care

Eligibility Criteria

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

You may qualify if:

• Male or female subjects, ages 18 years and older who have received a primary liver transplant from a deceased donor for end stage liver disease \*(ESLD).
• Women of child-bearing potential must have a negative serum pregnancy test at the time of screening and agree to use a medically acceptable method of contraception throughout the study and for 3 months following discontinuation of study treatment.

You may not qualify if:

• Recipients of multi-organ transplants.
• Recipients with positive crossmatch with their donor (current or previously).
• Subjects with a screening white blood cell count ≤ 2,000 mm3 or absolute neutrophil count (ANC) ≤ 1000, platelet count ≤ 100,000 mm3.
• Recipients with a hematocrit \< 32.
• History of malignancy within 5 years of enrollment (except for adequately treated basal cell or squamous cell carcinoma of the skin).
• Subjects who are positive for hepatitis C, hepatitis B surface antigen, or HIV.
• Subjects with previous intolerance to full dose MPA agent.
• Subjects with a history of acute rejection within 6 months prior to study enrollment.
• Subjects who have had chronic ductopenic rejection.
• Subjects who had rejection in the first-year post-transplant and are less than 3 years post-transplant.
• Subjects who had rejection requiring treatment with thymoglobulin or Orthoclone-OKT3 (OKT3) at anytime post-transplant.
• Original cause of ESLD related to autoimmune diseases such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis.
• Subjects who have received an investigational drug within 4 weeks of study entry.
• Subjects with a history of a psychological illness or condition such as to interfere with the subject's ability to understand the requirements of the study.
• Female subjects who are pregnant or nursing or females who are unwilling to use contraception during the study.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

University of Wisconsin- Madison

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Interventions

Mycophenolic Acid; Specimen Handling

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Results Point of Contact

• Title: Professor William Burlingham, PhD
• Organization: University of Wisconsin

BURLINGHAM@SURGERY.WISC.EDU

(608) 263-0119

Study Officials

• Will Burlingham, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

• Anthony D'Alessandro, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2010
• First Posted: October 29, 2010
• Study Start: November 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: June 1, 2012
• Last Updated: May 7, 2014
• Results First Posted: May 7, 2014

Record last verified: 2014-04

Locations

US (1)