Study of ISA247 (Voclosporin) in De Novo Renal Transplantation (PROMISE)
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ClinicalTrials.gov Identifier: NCT00270634 |
Recruitment Status
:
Completed
First Posted
: December 28, 2005
Results First Posted
: February 12, 2013
Last Update Posted
: February 12, 2013
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Kidney Diseases | Drug: Voclosporin Drug: tacrolimus | Phase 2 |
Prograf® (tacrolimus) is associated with numerous side effects, including neurotoxicity, nephrotoxicity, polyoma nephropathy, QT prolongation, and New Onset Diabetes Mellitus After Transplant (NODAT). Voclosporin is a novel calcineurin inhibitor intended for use in the prevention of organ graft rejection.
Comparison(s): Voclosporin at 3 dose levels (0.4, 0.6, and 0.8 mg/kg twice a day) compared to tacrolimus
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 334 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase IIb, Randomized, Multicenter, Open-Label, Concentration Controlled, Safety Study of ISA247 (Voclosporin) and Tacrolimus (Prograf®) in De Novo Renal Transplant Patients |
Study Start Date : | January 2006 |
Actual Primary Completion Date : | July 2009 |
Actual Study Completion Date : | July 2009 |

Arm | Intervention/treatment |
---|---|
Active Comparator: Low Dose Voclosporin
Low dose voclosporin
|
Drug: Voclosporin
voclosporin 0.4, 0.6, 0.8 mg/kg po BID
Other Name: ISA247
|
Active Comparator: Mid Dose Voclosporin
Mid Dose Voclosporin
|
Drug: Voclosporin
voclosporin 0.4, 0.6, 0.8 mg/kg po BID
Other Name: ISA247
|
Active Comparator: High Dose Voclosporin
High Dose Voclosporin
|
Drug: Voclosporin
voclosporin 0.4, 0.6, 0.8 mg/kg po BID
Other Name: ISA247
|
Active Comparator: Tacrolimus
Standard Dose Tacrolimus
|
Drug: tacrolimus
tacrolimus 0.05 mg/kg po BID
|
- Biopsy Proven Acute Rejection (BPAR) [ Time Frame: Six months ]The primary objective of the PROMISE trial was to demonstrate noninferiority of biopsy proven acute rejection (BPAR) rate in de novo renal transplant patients at 6 months in at least one VCS treatment group.
- To Demonstrate a 5% Improvement in Renal Function as Measured by Iothalamate Glomerular Filtration Rate (GFR) [ Time Frame: Six months ]ANOVAs to test for differences in GFR at Month 6.
- The Pharmacokinetic-pharmacodynamic Relationship Between Voclosporin and Calcineurin Inhibition (CNi), or Tacrolimus and Calcineurin Inhibition [ Time Frame: Six months ]
A sparse sampling protocol of whole blood samples obtained on Day 180 at time points immediately prior to drug administration and at 1, 2, and 4 hours post‐dose were utilized.
Standard non‐compartmental analysis (NCA) was performed on whole blood concentration data for voclosporin and its metabolites, tacrolimus, MPA (mycophenolic acid) and MPAG (mycophenolic acid glucuronide). Tmax and Cmax were obtained directly from the concentration‐time profiles without interpolation. AUC(0‐4)[area under the curve] was calculated using log‐linear trapezoidal rule. Cmax, AUC(0‐4), C0 and C2 were summarized using descriptive statistics.
- Patient Survival [ Time Frame: Six months ]
- Graft Survival [ Time Frame: Six months ]
- Hypertension, Hyperlipidemia, or Hyperglycemia [ Time Frame: Six months ]
- A Composite of Biopsy-proven Chronic Rejection Graft Loss, Death, or Lost to Follow up. [ Time Frame: Six months ]

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Ages Eligible for Study: | 18 Years to 65 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Males and females aged 18 - 65 years inclusive at the time of screening.
- Patients must be receiving a first cadaveric or living donor renal transplant.
- Patients must be able to receive oral medication at time of randomization.
- Females who are not 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 practicing a highly effective method of birth control. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly and will include implants, injectables, combined oral contraceptives, double-barrier method, sexual abstinence, or a sterile partner. Sexually-active men and women of child-bearing potential should continue to practice contraception as outlined above during treatment and for ≥ 3 months after the last dose of voclosporin.
- Able to give written informed consent prior to screening procedures.
- Able to keep study appointments and cooperate with all study requirements, in the opinion of the investigator.
Exclusion Criteria:
- Receiving a HLA (human leukocyte antigen)identical living related transplant.
- Cold ischemic time > 24 hours.
- Peak PRA (panel reactive antibodies) > 30%
- Cadaveric donors who are over age 60, non-heart beating donors, or any cadaveric donors positive for HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV).
- Transplantation of multiple grafts (e.g. kidney and pancreas).
- Systemic infections requiring continued therapy at the time of entry into this study. (Prophylaxis against cytomegalovirus [CMV] and/or pneumocystis carinii pneumonia (PCP) infection will be permitted).
- Serologic evidence or known latent human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C (HCV) virus. Known negative serology prior to study entry may be used.
- 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 electrodesiccation.
- Requires prohibited medications or treatment during the study.
- Alanine transaminase (ALT), aspartate transaminase (AST), or gamma-glutamyl transferase (GGT) ≥ 3x upper limit of normal (ULN) at time of transplantation.
- White blood cell count ≤ 2.8 x 10^9/L.
- Triglycerides ≥ 3x ULN.
- Pregnant women or nursing mothers.
- Has used any investigational drug or device within 28 days or 5 half lives (whichever is longer) prior to enrollment.
- Previous exposure to voclosporin.
- A history of active alcoholism or drug addiction within 1 year prior to study entry.
- Weighs < 45 kg (99 lbs) or > 140 kg (308 lbs).
- A history of disease, including mental/emotional disorder that would interfere with the subject's participation in the study, or that might cause the administration of voclosporin to pose a significant risk to the subject, in the opinion of the investigator.
- Allergy to iodine.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00270634

United States, Alabama | |
Isotechnika Investigational Site | |
Birmingham, Alabama, United States, 35924 | |
United States, California | |
Isotechnika Investigational Site | |
Los Angeles, California, United States, 90033 | |
Isotechnika Investigational Site | |
Los Angeles, California, United States, 90057 | |
Isotechnika Investigational Site | |
Los Angeles, California, United States, 90095-7306 | |
Isotechnika Investigational Site | |
Orange, California, United States, 92868 | |
Isotechnika Investigational Site | |
Palo Alto, California, United States, 94304-1510 | |
Isotechnika Investigational Site | |
San Diego, California, United States, 92123 | |
Isotechnika Investigational Site | |
San Francisco, California, United States, 94143-0116 | |
United States, Colorado | |
Isotechnika Investigational Site | |
Denver, Colorado, United States, 80262 | |
United States, Florida | |
Isotechnika Investigational Site | |
Gainesville, Florida, United States, 32610 | |
Isotechnika Investigational Site | |
Tampa, Florida, United States, 33606 | |
United States, Illinois | |
Isotechnika Investigational Site | |
Chicago, Illinois, United States, 60611 | |
Isotechnika Investigational Site | |
Chicago, Illinois, United States, 60637 | |
United States, Kentucky | |
Isotechnika Investigational Site | |
Lexington, Kentucky, United States, 40536 | |
United States, Louisiana | |
Isotechnika Investigational Site | |
New Orleans, Louisiana, United States, 70112 | |
Isotechnika Investigational Site | |
New Orleans, Louisiana, United States, 70121 | |
United States, Maryland | |
Isotechnika Investigational Site | |
Baltimore, Maryland, United States, 21201 | |
United States, Massachusetts | |
Isotechnika Investigational Site | |
Boston, Massachusetts, United States, 02215 | |
United States, Michigan | |
Isotechnika Investigational Site | |
Ann Arbor, Michigan, United States, 48109-9623 | |
Isotechnika Investigational Site | |
Detroit, Michigan, United States, 48202 | |
United States, Minnesota | |
Isotechnika Investigational Site | |
Rochester, Minnesota, United States, 55905 | |
United States, New Jersey | |
Isotechnika Investigational Site | |
Livingston, New Jersey, United States, 07039 | |
United States, New York | |
Isotechnika Investigational Site | |
Buffalo, New York, United States, 14203 | |
Isotechnika Investigational Site | |
Hawthorne, New York, United States, 10532 | |
Isotechnika Investigational Site | |
New York, New York, United States, 10021 | |
Isotechnika Investigational Site | |
Rochester, New York, United States, 14642-8410 | |
United States, North Carolina | |
Isotechnika Investigational Site | |
Durham, North Carolina, United States, 27705 | |
Isotechnika Investigational Site | |
Winston-Salem, North Carolina, United States, 27157 | |
United States, Ohio | |
Isotechnika Investigational Site | |
Cincinnati, Ohio, United States, 45219 | |
Isotechnika Investigational Site | |
Cincinnati, Ohio, United States, 45267-0585 | |
United States, Oregon | |
Isotechnika Investigational Site | |
Portland, Oregon, United States, 97210 | |
Isotechnika Investigational Site | |
Portland, Oregon, United States, 97239-2940 | |
Isotechnika Investigational Site | |
Portland, Oregon, United States, 97329-2940 | |
United States, Pennsylvania | |
Isotechnika Investigational Site | |
Philadelphia, Pennsylvania, United States, 19102 | |
Isotechnika Investigational Site | |
Philadelphia, Pennsylvania, United States, 19104 | |
United States, South Carolina | |
Isotechnika Investigational Site | |
Charleston, South Carolina, United States, 29425 | |
United States, Tennessee | |
Isotechnika Investigational Site | |
Memphis, Tennessee, United States, 38104 | |
United States, Texas | |
Isotechnika Investigational Site | |
Dallas, Texas, United States, 75246 | |
Isotechnika Investigational Site | |
Houston, Texas, United States, 77030 | |
United States, Virginia | |
Isotechnika Investigational Site | |
Richmond, Virginia, United States, 23298 | |
Canada, Alberta | |
Isotechnika Investigational Site | |
Edmonton, Alberta, Canada, T6G 2G3 | |
Canada, Ontario | |
Isotechnika Investigational Site | |
London, Ontario, Canada, N6A 5A5 | |
Isotechnika Investigational Site | |
Toronto, Ontario, Canada, M5C 2T2 | |
Canada, Quebec | |
Isotechnika Investigational Site | |
Montreal, Quebec, Canada, H3A 1A1 | |
Canada, Saskatchewan | |
Isotechnika Investigational Site | |
Saskatoon, Saskatchewan, Canada, S7M 0Z9 |
Study Director: | Daniel Abramowicz, MD, PhD | Erasme Hospital | |
Study Director: | Philip Belitsky, MD | No Affiliation | |
Study Director: | Arthur Matas, MD | University of Minnesota - Clinical and Translational Science Institute | |
Study Director: | Mark Pescovitz, MD | Indiana University | |
Study Director: | A. Osama Gaber, MD | The Methodist Hospital System |
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Aurinia Pharmaceuticals Inc. |
ClinicalTrials.gov Identifier: | NCT00270634 History of Changes |
Other Study ID Numbers: |
ISA05-01 |
First Posted: | December 28, 2005 Key Record Dates |
Results First Posted: | February 12, 2013 |
Last Update Posted: | February 12, 2013 |
Last Verified: | February 2013 |
Keywords provided by Aurinia Pharmaceuticals Inc.:
Randomized Controlled Trials Immunosuppression Adult Kidney Transplantation Treatment Outcome |
Additional relevant MeSH terms:
Kidney Diseases Urologic Diseases Tacrolimus Cyclosporine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |
Calcineurin Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antifungal Agents Anti-Infective Agents Dermatologic Agents Antirheumatic Agents |