Clinical trial NCT01586845: Safety and Efficacy Study of Voclosporin and Tacrolimus in Transplantation
Official title: A Phase III, Randomized, Multicentre, Open-Label, Concentration-Controlled, Safety and Efficacy Study of Voclosporin and Tacrolimus in Renal Transplantation
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Renal Transplantation
Keywords: Randomized Controlled Trials
Immunosuppression
Adult
Kidney Transplantation
Treatment Outcome
Lead sponsor: Aurinia Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2012-04-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The primary endpoint to assess non-inferiority will be efficacy failure at the end of Month 12 after randomization.
timeFrame: 1 Year post-Transplant
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Busque S, Cantarovich M, Mulgaonkar S, Gaston R, Gaber AO, Mayo PR, Ling S, Huizinga RB, Meier-Kriesche HU; PROMISE Investigators. The PROMISE study: a phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de novo kidney transplantation. Am J Transplant. 2011 Dec;11(12):2675-84. doi: 10.1111/j.1600-6143.2011.03763.x. Epub 2011 Sep 22.
citation: Kuglstatter A, Mueller F, Kusznir E, Gsell B, Stihle M, Thoma R, Benz J, Aspeslet L, Freitag D, Hennig M. Structural basis for the cyclophilin A binding affinity and immunosuppressive potency of E-ISA247 (voclosporin). Acta Crystallogr D Biol Crystallogr. 2011 Feb;67(Pt 2):119-23. doi: 10.1107/S0907444910051905. Epub 2011 Jan 15.
citation: Birsan T, Dambrin C, Freitag DG, Yatscoff RW, Morris RE. The novel calcineurin inhibitor ISA247: a more potent immunosuppressant than cyclosporine in vitro. Transpl Int. 2005 May;17(12):767-71. doi: 10.1007/s00147-004-0799-z. Epub 2005 Apr 13.