Safety and Efficacy Study of Voclosporin and Tacrolimus in Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the efficacy and safety of voclosporin administered orally twice daily for the prevention of acute allograft rejection in recipients of a kidney transplant.

Detailed Description
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This will be a phase III, randomized, multicentre, open-label, concentration-controlled study in subjects undergoing a first or second renal transplant, with induction immunosuppression with an IL-2 receptor antibody (basiliximab), mycophenolate mofetil and steroids. The primary endpoint to assess non-inferiority will be efficacy failure at the end of Month 12 after randomization.

Official Title
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A Phase III, Randomized, Multicentre, Open-Label, Concentration-Controlled, Safety and Efficacy Study of Voclosporin and Tacrolimus in Renal Transplantation

Conditions
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Renal Transplantation

Intervention / Treatment
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* Drug: voclosporin
* Drug: tacrolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged 18-65 years inclusive at the time of screening. Recipients of a first or second deceased donor or living donor renal transplant. Exclusion Criteria: Subjects presently receiving immunosuppression for a previously failed transplant. Females who are pregnant or nursing or planning to become pregnant during the course of the study, or 3 months after last dose of study medication. Sexually-active women of child-bearing potential (including those who are < 1 year postmenopausal) and sexually-active men who are not practicing a highly effective method of birth control. Subjects receiving a HLA identical living related transplant. Subjects wth a positive T-cell lymphocytotoxic cross match, or positive flow T and B cell cross match. Subjects undergoing primary transplant with a current PRA (or CPRA) ≥ 25%. Subjects who experienced graft loss within 1 year of transplant. Subjects receiving a kidney from a ABO incompatible donor. Subjects receiving a kidney from a deceased donor positive for HIV, HBV, HCV or tuberculosis. Subjects receiving a a kidney from a non-heart beating donor. Subjects receiving paired (en bloc or paired) kidney transplants. Transplantation of multiple grafts (e.g. kidney and pancreas). Subjects receiving a kidney with a cold ischemia time > 30 hours. Subjects receiving any transplanted organ other than a kidney. Recipients of a bone marrow or stem cell transplant. Any systemic infections requiring continued therapy at the time of entry into this study. (Prophylaxis against CMV and/or PCP infection will be permitted). Subjects with positive results of the following serological tests: HIV I Ab, hepatitis B virus (HBV) surface antigen (HBsAg), anti-hepatitis B core antibody (HBcAb), and the anti-hepatitis C virus antibody (HCV Ab). Negative results for these serological tests must be documented within 12 months prior to randomization. Subjects with active tuberculosis (Tb) requiring treatment within the last 3 years. Subjects with a known positive purified protein derivative (PPD) test are not eligible unless they have completed treatment for latent Tb and have a negative chest X-ray at time of enrollment. PPD testing must have been done within the last 12 months, and a positive result is defined as ≥ 10 mm induration, a Heaf score of >1 in non-Bacille Calmette-Guérin (BCG) immunized subjects, or >2 in BCG immunized subjects. Subjects with a current malignancy or history of malignancy within 5 years or a history of lymphoma at any time. Subjects can be enrolled with a history of squamous or basal cell carcinoma that has been surgically excised or removed with curettage and electrodessication.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Voclosporin<br>Voclosporin | Drug: voclosporin<br>* Initial dose of voclosporin 0.8 mg/kg BID, then concentration controlled<br>* Other names: voclosporin, ISA247;|
| Active Comparator: Tacrolimus<br>Tacrolimus | Drug: tacrolimus<br>* tacrolimus as per labeled dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint to assess non-inferiority will be efficacy failure at the end of Month 12 after randomization. | FDA Efficacy Failure is biopsy-proven acute rejection (BPAR, Banff Grade ≥ 1A as determined by the central pathologist) where subjects who experience death, graft loss (return to dialysis for >30 days, allograft nephrectomy or re-transplantation), or lost to follow-up are included in the analysis as treatment failures. EMA Efficacy Failure includes any subject experiencing any of the following: biopsy-proven acute rejection (BPAR, Banff Grade ≥ 1A as determined by the central pathologist), death, graft loss or graft dysfunction (Cockcroft-Gault CrCl < 40 mL/min). | 1 Year post-Transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Randomized Controlled Trials, Immunosuppression, Adult, Kidney Transplantation, Treatment Outcome