Kidney DiseasesPhase 2PROMISENCT00270634
Study of ISA247 (Voclosporin) in De Novo Renal Transplantation
A Phase 2 study testing Voclosporin and tacrolimus in people with Kidney Diseases, run by Aurinia Pharmaceuticals Inc. at 45 sites in 2 countries.
Trial summary
This study will see if voclosporin is safe and effective in preventing kidney transplant rejection. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Kidney Diseases
- What is being tested?
- Voclosporin and tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 334 participants
- Where
- 45 sitesin 2 countries
- Study dates
- Jan 2006to Jul 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Show all 19Show fewer
- 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.
Trial locations and contacts
45 sites in 2 countries.
45 sites in 2 countries
United States40 sites
Isotechnika Investigational Site
Ann Arbor, Michigan, 48109-9623
Isotechnika Investigational Site
Baltimore, Maryland, 21201
Isotechnika Investigational Site
Birmingham, Alabama, 35924
Isotechnika Investigational Site
Boston, Massachusetts, 02215
Isotechnika Investigational Site
Buffalo, New York, 14203
Isotechnika Investigational Site
Charleston, South Carolina, 29425
Isotechnika Investigational Site
Chicago, Illinois, 60611
Isotechnika Investigational Site
Chicago, Illinois, 60637
Isotechnika Investigational Site
Cincinnati, Ohio, 45219
Isotechnika Investigational Site
Cincinnati, Ohio, 45267-0585
Isotechnika Investigational Site
Dallas, Texas, 75246
Isotechnika Investigational Site
Denver, Colorado, 80262
Isotechnika Investigational Site
Detroit, Michigan, 48202
Isotechnika Investigational Site
Durham, North Carolina, 27705
Isotechnika Investigational Site
Gainesville, Florida, 32610
Isotechnika Investigational Site
Hawthorne, New York, 10532
Isotechnika Investigational Site
Houston, Texas, 77030
Isotechnika Investigational Site
Lexington, Kentucky, 40536
Isotechnika Investigational Site
Livingston, New Jersey, 07039
Isotechnika Investigational Site
Los Angeles, California, 90033
Isotechnika Investigational Site
Los Angeles, California, 90057
Isotechnika Investigational Site
Los Angeles, California, 90095-7306
Isotechnika Investigational Site
Memphis, Tennessee, 38104
Isotechnika Investigational Site
New Orleans, Louisiana, 70112
Isotechnika Investigational Site
New Orleans, Louisiana, 70121
Isotechnika Investigational Site
New York, New York, 10021
Isotechnika Investigational Site
Orange, California, 92868
Isotechnika Investigational Site
Palo Alto, California, 94304-1510
Isotechnika Investigational Site
Philadelphia, Pennsylvania, 19102
Isotechnika Investigational Site
Philadelphia, Pennsylvania, 19104
Isotechnika Investigational Site
Portland, Oregon, 97210
Isotechnika Investigational Site
Portland, Oregon, 97239-2940
Isotechnika Investigational Site
Portland, Oregon, 97329-2940
Isotechnika Investigational Site
Richmond, Virginia, 23298
Isotechnika Investigational Site
Rochester, Minnesota, 55905
Isotechnika Investigational Site
Rochester, New York, 14642-8410
Isotechnika Investigational Site
San Diego, California, 92123
Isotechnika Investigational Site
San Francisco, California, 94143-0116
Isotechnika Investigational Site
Tampa, Florida, 33606
Isotechnika Investigational Site
Winston-Salem, North Carolina, 27157
Canada5 sites
Isotechnika Investigational Site
Edmonton, Alberta, T6G 2G3
Isotechnika Investigational Site
London, Ontario, N6A 5A5
Isotechnika Investigational Site
Montreal, Quebec, H3A 1A1
Isotechnika Investigational Site
Saskatoon, Saskatchewan, S7M 0Z9
Isotechnika Investigational Site
Toronto, Ontario, M5C 2T2
About this study
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
This study will see if voclosporin is safe and effective in preventing kidney transplant rejection.
Read the detailed description
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
- Conditions
- Kidney Diseases
- Being tested
- Voclosporin, tacrolimus
- Keywords
- Randomized Controlled Trials, Immunosuppression, Adult, Kidney Transplantation, Treatment Outcome
- Medical subject headings
- Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VoclosporinDrug
Also called ISA247
voclosporin 0.4, 0.6, 0.8 mg/kg po BID
tacrolimusDrug
tacrolimus 0.05 mg/kg po BID
| Study group | Role | What they receive |
|---|---|---|
| Low Dose Voclosporin | Active comparator | Low dose voclosporin Receives: Drug: Voclosporin |
| Mid Dose Voclosporin | Active comparator | Mid Dose Voclosporin Receives: Drug: Voclosporin |
| High Dose Voclosporin | Active comparator | High Dose Voclosporin Receives: Drug: Voclosporin |
| Tacrolimus | Active comparator | Standard Dose Tacrolimus Receives: Drug: tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biopsy Proven Acute Rejection (BPAR)
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.
Measured: Six months
Secondary outcomes (6)
To Demonstrate a 5% Improvement in Renal Function as Measured by Iothalamate Glomerular Filtration Rate (GFR)
ANOVAs to test for differences in GFR at Month 6.
Measured: Six months
The Pharmacokinetic-pharmacodynamic Relationship Between Voclosporin and Calcineurin Inhibition (CNi), or Tacrolimus and Calcineurin Inhibition
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.
Measured: Six months
Patient Survival
Measured: Six months
Graft Survival
Measured: Six months
Hypertension, Hyperlipidemia, or Hyperglycemia
Measured: Six months
A Composite of Biopsy-proven Chronic Rejection Graft Loss, Death, or Lost to Follow up.
Measured: Six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2005 (estimated)
- Study startJan 2006
- Primary completionJul 2009
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Kidney DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 334 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aurinia Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Daniel Abramowicz, MD, PhD, Study director, Erasme University HospitalPhilip Belitsky, MD, Study director, No AffiliationArthur Matas, MD, Study director, University of MinnesotaMark Pescovitz, MD, Study director, Indiana UniversityA. Osama Gaber, MD, Study director, The Methodist Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00270634
- Sponsor's protocol ID
- ISA05-01
- Acronym
- PROMISE
- Status last verified
- Feb 2013
- First submitted
- 23 Dec 2005
- Last updated
- 12 Feb 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Gregory CR, Kyles AE, Bernsteen L, Wagner GS, Tarantal AF, Christe KL, Brignolo L, Spinner A, Griffey SM, Paniagua RT, Hubble RW, Borie DC, Morris RE. Compared with cyclosporine, ISATX247 significantly prolongs renal-allograft survival in a nonhuman primate model. Transplantation. 2004 Sep 15;78(5):681-5. doi: 10.1097/01.tp.0000131950.75697.71.
PubMed 15371668Stalder M, Birsan T, Hubble RW, Paniagua RT, Morris RE. In vivo evaluation of the novel calcineurin inhibitor ISATX247 in non-human primates. J Heart Lung Transplant. 2003 Dec;22(12):1343-52. doi: 10.1016/s1053-2498(03)00033-0.
PubMed 14672749Abel MD, Aspeslet LJ, Freitag DG, Naicker S, Trepanier DJ, Kneteman NM, Foster RT, Yatscoff RW. ISATX247: a novel calcineurin inhibitor. J Heart Lung Transplant. 2001 Feb;20(2):161. doi: 10.1016/s1053-2498(00)00290-4. No abstract available.
PubMed 11250240Busque 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.
PubMed 21943027Mayo PR, Ling SY, Huizinga RB, Freitag DG, Aspeslet LJ, Foster RT. Population PKPD of voclosporin in renal allograft patients. J Clin Pharmacol. 2014 May;54(5):537-45. doi: 10.1002/jcph.237. Epub 2013 Nov 30.
PubMed 24243422
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00270634
- Acronym / sponsor ID
- PROMISE / ISA05-01
- Conditions
- Kidney Diseases
- Keywords
- Randomized Controlled Trials, Immunosuppression, Adult, Kidney Transplantation, Treatment Outcome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 334 participants (actual)
- Lead sponsor
- Aurinia Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2006
- Primary completion
- Jul 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 28 Dec 2005 (estimated)
- Results
- Posted 12 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will see if voclosporin is safe and effective in preventing kidney transplant rejection.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Low Dose Voclosporin | Active comparator | Drug: VoclosporinLow dose voclosporin |
| Mid Dose Voclosporin | Active comparator | Drug: VoclosporinMid Dose Voclosporin |
| High Dose Voclosporin | Active comparator | Drug: VoclosporinHigh Dose Voclosporin |
| Tacrolimus | Active comparator | Drug: tacrolimusStandard Dose Tacrolimus |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (19 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VoclosporinAlso: ISA247voclosporin 0.4, 0.6, 0.8 mg/kg po BID | Drug | High Dose Voclosporin, Low Dose Voclosporin, Mid Dose Voclosporin |
| tacrolimustacrolimus 0.05 mg/kg po BID | Drug | Tacrolimus |
Primary outcome
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.
6 secondary outcomes
To Demonstrate a 5% Improvement in Renal Function as Measured by Iothalamate Glomerular Filtration Rate (GFR)
Time frame: Six months
The Pharmacokinetic-pharmacodynamic Relationship Between Voclosporin and Calcineurin Inhibition (CNi), or Tacrolimus and Calcineurin Inhibition
Time frame: Six months
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15371668Gregory CR, Kyles AE, Bernsteen L, Wagner GS, Tarantal AF, Christe KL, Brignolo L, Spinner A, Griffey SM, Paniagua RT, Hubble RW, Borie DC, Morris RE. Compared with cyclosporine, ISATX247 significantly prolongs renal-allograft survival in a nonhuman primate model. Transplantation. 2004 Sep 15;78(5):681-5. doi: 10.1097/01.tp.0000131950.75697.71.
- Background: PubMed 14672749Stalder M, Birsan T, Hubble RW, Paniagua RT, Morris RE. In vivo evaluation of the novel calcineurin inhibitor ISATX247 in non-human primates. J Heart Lung Transplant. 2003 Dec;22(12):1343-52. doi: 10.1016/s1053-2498(03)00033-0.
- Background: PubMed 11250240Abel MD, Aspeslet LJ, Freitag DG, Naicker S, Trepanier DJ, Kneteman NM, Foster RT, Yatscoff RW. ISATX247: a novel calcineurin inhibitor. J Heart Lung Transplant. 2001 Feb;20(2):161. doi: 10.1016/s1053-2498(00)00290-4. No abstract available.
- Results publication: PubMed 21943027Busque 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.
- Derived from this study: PubMed 24243422Mayo PR, Ling SY, Huizinga RB, Freitag DG, Aspeslet LJ, Foster RT. Population PKPD of voclosporin in renal allograft patients. J Clin Pharmacol. 2014 May;54(5):537-45. doi: 10.1002/jcph.237. Epub 2013 Nov 30.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Abramowicz, MD, PhD study director
Erasme University Hospital
Philip Belitsky, MD study director
No Affiliation
Arthur Matas, MD study director
University of Minnesota
45 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Voclosporin and tacrolimus in people with Kidney Diseases, run by Aurinia Pharmaceuticals Inc. at 45 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biopsy Proven Acute Rejection (BPAR) (time frame: Six months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00270634, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2013.