Evaluate Effects and Safety of Pre-load Myfortic® in Transplant Patients

A 12-month, Prospective, Randomized, Dual Center, Open Label Pilot Study to Evaluate the Safety and Efficacy of Myfortic® (Mycophenolic Acid) Loading Regimens in Combination With Thymoglobulin® [Anti-thymocyte Globulin (Rabbit)] or Simulect® (Basiliximab) Induction and Prograf® (Tacrolimus) in Early Corticosteroid Withdrawal

This study is specifically designed to determine whether the initiation of Myfortic 2 weeks prior to transplantation will enhance the therapeutic efficacy of Simulect induction therapy in low to moderate risk patients. Specifically, the addition of Myfortic pretransplant to Simulect induction will be compared to standard Myfortic therapy with Thymoglobulin induction starting at the time of transplant in kidney transplant recipients.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant Recipients
• Intervention / Treatment: Drug: mycophenolic acid

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients capable of understanding the purposes and risks of the study.
• Patients who can give written informed consent, and who are willing and able to participate in the full course of the study.
• Women of childbearing potential must have a negative serum pregnancy test within the last 48 hours prior to receiving study medication.
• Women of childbearing potential must use two reliable forms of contraception simultaneously, unless they are status post bilateral tubal ligation, bilateral oophorectomy, or hysterectomy. Effective contraception must be used before beginning study drug therapy, for the duration of the study and for 6 weeks following completion of the study.

Exclusion Criteria:

• Patients who are recipients of a multiple organ transplant or if the patient previously received and organ transplant.
• Patients who are recipients of A-B-O incompatible transplants, all complement-dependent cytotoxicity (CDC) crossmatch positive transplants.
• Sensitized patients [most recent anti-Human Leukocyte Antigens (HLA) Class I panel reactive antibody (PRA) ≥ 25% by a CDC-based assay].
• Recipient or donor is known to be seropositive for hepatitis C virus (HCV) or B virus (HBV) except for hepatitis B surface antibody positive.
• Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV).
• Patient has uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives.
• Patients with thrombocytopenia (<75,000/mm3 ), with an absolute neutrophil count of < 1,500/mm3); and/or leucopoenia (< 2,500/mm3), or anemia (hemoglobin < 6 g/dL) prior to study inclusion.
• Patient is taking or has been taking an investigational drug in the 30 days prior to transplant.
• Patient has a known hypersensitivity to tacrolimus, mycophenolate mofetil, enteric-coated mycophenolic acid, rabbit anti-thymocyte globulin, or corticosteroids.
• Patients with severe diarrhea or other gastrointestinal disorders that might interfere with their ability to absorb oral medication; diabetic patients with previously diagnosed diabetic gastroenteropathy, or patients with active peptic ulcer disease.
• Patient is receiving chronic steroid therapy at the time of transplant.
• Patients with a history of malignancy within the last five years, except for successfully excised squamous or basal cell carcinoma of the skin.
• Patient is pregnant or lactating, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by positive human Chorionic Gonadotropin (hCG) laboratory test.
• Patient has any form of substance abuse, psychiatric disorder or a condition that, in the opinion of the investigator, may invalidate communication with the investigator.
• Inability to cooperate or communicate with the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Myfortic preload; Initiation of mycophenolic acid (Myfortic) 2 weeks prior to transplantation (with Simulect induction at time of transplant)	Drug: mycophenolic acid; Comparing mycophenolic acid 720mg orally twice daily starting 2 weeks prior to transplant to mycophenolic acid 720mg orally twice daily starting day of transplant.; Other Names: Myfortic
Active Comparator: Myfortic standard; mycophenolic acid (Myfortic) at time of transplant with Thymoglobulin induction	Drug: mycophenolic acid; Comparing mycophenolic acid 720mg orally twice daily starting 2 weeks prior to transplant to mycophenolic acid 720mg orally twice daily starting day of transplant.; Other Names: Myfortic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Biopsy-confirmed Acute Rejection by Banff '97 Criteria (Updated 2007) 3, 6 and 12 Months Post Transplant	Incidence of biopsy-confirmed acute rejection by Banff '97 Criteria (updated 2007) post transplant. The acute form of T-cell mediated rejection is furthermore subclassified as follows. Since this is the most common form of rejection, it is useful to know: As with humoral rejection, there are both acute & chronic forms: The acute form of T-cell mediated rejection is furthermore subclassified as follows. Since this is the most common form of rejection, it is useful to know: Class IA: there is at least 25% of parenchymal showing interstitial infiltration and foci of moderate tubulitis (defined as a certain number of immune cells present in tubular cross-sections). Class IB: just like Class IA except there is more severe tubulitis. Class IIA: there is mild-to-moderate intimal arteritis. Class IIB: there is severe intimal arteritis comprising at least 25% of the lumenal area. Class III: there is transmural (e.g. the full vessel wall thickness) arteritis.	3, 6 and 12 months post transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of Acute Rejection by Banff '97 Criteria	Severity of biopsy-confirmed acute rejection by Banff '97 Criteria (updated 2007) at 1 year. The acute form of T-cell mediated rejection is furthermore subclassified as follows. Since this is the most common form of rejection, it is useful to know: As with humoral rejection, there are both acute & chronic forms: The acute form of T-cell mediated rejection is furthermore subclassified as follows. Since this is the most common form of rejection, it is useful to know: Class IA: there is at least 25% of parenchymal showing interstitial infiltration and foci of moderate tubulitis (defined as a certain number of immune cells present in tubular cross-sections). Class IB: just like Class IA except there is more severe tubulitis. Class IIA: there is mild-to-moderate intimal arteritis. Class IIB: there is severe intimal arteritis comprising at least 25% of the lumenal area. Class III: there is transmural (e.g. the full vessel wall thickness) arteritis.	Severity 1 year post transplant
Difference in Renal Function	Difference in renal function between groups at listed time points assessed by mean serum creatinine. Increased serum creatinine could indicate worsening renal function. A "normal" serum creatinine range for the transplant population varies by patient, but a typical range for Scr would be 1-2 mg/dL.	Difference at 1 month, 3 months, 6 months, 1 year
Incidence of Chronic Alloantibody Rejection or Chronic Allograft Arteriopathy by Banff '97	The Banff features suggestive of chronic rejection were: a) chronic transplant glomerulopathy: Glomerular basement membrane duplication and mesangial cell proliferation, and b) vasculopathy: Fibrous intimal thickening often with fragmentation of internal elastic lamina. Chronic changes in the interstitium (ci), tubules (ct), vessels (cv), and glomerulus (cg) were likewise graded into 0, 1, 2, and 3. The severity of interstitial fibrosis and tubular atrophy, as also chronic transplant glomerulopathy and vasculopathy were used to grade chronic allograft changes.	1 year
Number of Patients Requiring Anti-lymphocyte Therapy for Acute Rejection		1 year

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: Novartis Pharmaceuticals
• Investigators: Principal Investigator: Adele Shields, Pharm.D., University of Cincinnati

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: October 28, 2010
• First Submitted That Met QC Criteria: April 14, 2011
• First Posted (Estimate): April 15, 2011

Study Record Updates

• Last Update Posted (Estimate): August 2, 2016
• Last Update Submitted That Met QC Criteria: July 5, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: Myfortic Preload