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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00483756




Registration number
NCT00483756
Ethics application status
Date submitted
6/06/2007
Date registered
7/06/2007
Date last updated
14/03/2013

Titles & IDs
Public title
Study of a JAK3 Inhibitor for the Prevention of Acute Rejection in Kidney Transplant Patients
Scientific title
A Phase 2 Randomized, Multicenter, Active Comparator-Controlled Trial to Evaluate the Safety and Efficacy of Co-administration of CP-690,550 and Mycophenolate Mofetil / Mycophenolate Sodium in De Novo Renal Allograft Recipients
Secondary ID [1] 0 0
A3921030
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Kidney Transplantation 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cyclosporine
Treatment: Drugs - CP-690,550
Treatment: Drugs - CP-690,550

Active Comparator: 1 - Treatment Arm 1 will also receive standard of care medications

Experimental: 2 - Treatment Arm 2 will also receive standard of care medications

Experimental: 3 - Treatment Arm 3 will also receive standard of care medications


Treatment: Drugs: Cyclosporine
Standard of care

Treatment: Drugs: CP-690,550
CP-690,550 15 mg BID for Months 1-6, then 10 mg BID for Months 7-12

Treatment: Drugs: CP-690,550
CP-690,550 15 mg BID for Months 1-3, then 10 mg BID for Months 4-12

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With First Clinical Biopsy Proven Acute Rejection (BPAR) Episode 6 Months Post-Transplant - Clinical BPAR was a BPAR (category acute rejection as interpreted by the central blinded pathologist according to the Banff 97 working classification) associated with an increase in serum creatinine of >= 0.3 milligram per deciliter (mg/dL) and >=20 percent (%) from pre-rejection baseline. The increase in serum creatinine was assessed based on the comparison of baseline and the highest serum creatinine recorded within 24 hours (hrs) of the time of biopsy.
Timepoint [1] 0 0
Baseline up to Month 6
Primary outcome [2] 0 0
Glomerular Filtration Rate (GFR) at Month 12 - GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was calculated using iohexol serum clearance. For determination of iohexol serum clearance, iohexol was administered as an intravenous bolus over 5 minutes immediately after morning dosing of CP-690,550 or CsA on day of GFR evaluation. A normal GFR is greater than (>) 90 milliliter per minute (mL/min), although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR less than (<) 15 mL/min indicated kidney failure.
Timepoint [2] 0 0
2, 3, 4, and 5 hrs post iohexol intravenous bolus at Month 12
Secondary outcome [1] 0 0
Glomerular Filtration Rate (GFR) at Month 6 - GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was calculated using iohexol serum clearance. For determination of iohexol serum clearance, iohexol was administered as an intravenous bolus over 5 minutes immediately after morning dosing of CP-690,550 or CsA on day of GFR evaluation. A normal GFR is >90 mL/min, although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR <15 mL/min indicated kidney failure.
Timepoint [1] 0 0
2, 3, 4, and 5 hrs post iohexol intravenous bolus at Month 6
Secondary outcome [2] 0 0
Number of Participants With Progression of Chronic Allograft Lesions at Month 12 - Progression of chronic allograft lesions was defined as an increase in the Banff chronicity score (Banff-CS) in biopsy from the implantation (baseline) biopsy in a given participant. Banff-CS was the sum of the Banff scores for the 4 chronic basic lesions (allograft glomerulopathy [cg] + interstitial fibrosis [ci] + tubular atrophy [ct] + vascular intimal thickening [cv]).The Banff-CS ranged from 0-12, higher score indicated greater lesions and Month 12 Banff-CS greater than the implantation biopsy score indicated progression of lesions.
Timepoint [2] 0 0
Month 12
Secondary outcome [3] 0 0
Number of Participants With First Clinical Biopsy Proven Acute Rejection (BPAR) 12 Months Post Transplant - Clinical BPAR was a BPAR (category acute rejection as interpreted by the central blinded pathologist according to the Banff 97 working classification) associated with an increase in serum creatinine of >= 0.3 mg/dL and >=20% from pre-rejection baseline. The increase in serum creatinine was assessed based on the comparison of baseline and the highest serum creatinine recorded within 24 hrs of the time of biopsy.
Timepoint [3] 0 0
Baseline up to Month 12
Secondary outcome [4] 0 0
Number of Participants With Treated Clinical Acute Rejection - Treated clinical acute rejection was defined as an acute rejection episode that was diagnosed based on local biopsy readout and received anti-rejection treatment.
Timepoint [4] 0 0
Month 6, 12
Secondary outcome [5] 0 0
Number of Participants With Combined Banff Rejection Categories (Categories 2, 3, and 4) - Banff 97: standard classification for scoring and classifying rejection of kidney transplant biopsies in 6 diagnostic categories: normal, antibody-mediated rejection, borderline changes: 'suspicious' for acute cellular rejection, acute/active cellular rejection, chronic/sclerosing allograft nephropathy, and other. Combined Banff rejection calculated from categories of antibody-mediated rejection (Category 2) plus borderline changes (Category 3) plus acute rejection (Category 4), as interpreted by the central pathologist.
Timepoint [5] 0 0
Month 6, 12
Secondary outcome [6] 0 0
Number of Participants With Graft Loss - Graft loss was defined as graft nephrectomy, participant death, re-transplantation, or return to dialysis for >=6 consecutive weeks.
Timepoint [6] 0 0
Month 6, 12
Secondary outcome [7] 0 0
Number of Participants With Efficacy Failure - Efficacy failure was the first occurrence of clinical BPAR diagnosed by the central pathologist or graft loss including participant death.
Timepoint [7] 0 0
Month 6, 12
Secondary outcome [8] 0 0
Number of Participants Who Died
Timepoint [8] 0 0
Month 6, 12
Secondary outcome [9] 0 0
Lymphocyte Subset - The absolute cell counts of cluster of differentiation 3 (CD3): T-lymphocytes, cluster of differentiation 19 (CD19): B-lymphocytes, and cluster of differentiation 56 (CD56): assumed natural killer cells, were determined using flow cytometry.
Timepoint [9] 0 0
Month 1, 3, 6, 12
Secondary outcome [10] 0 0
Population Pharmacokinetics (PK) - Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Timepoint [10] 0 0
Pre-dose-2(P-2), Pre-dose(P), 0.5,1,2 hr post-dose(PD) on Day14, Month(M) 3; P,1,2 hr PD on M1; P, 0.5, 2, 4 hr PD on M6; P-2, P, 0.5 hr PD on M9, M12 as per randomization in CP-690,550 treated; P on M3 and P, 2, 4 hr PD on M6 in CsA treated participants
Secondary outcome [11] 0 0
Glomerular Filtration Rate (GFR) by The Nankivell Equation - GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was measured directly or estimated using established formulas. GFR was calculated was estimated by creatinine clearance (CLcr) using Nankivell equation. CLcr by Nankivell equation= (6.7 per serum creatinine) plus (0.25*body weight) minus (0.5*serum urea) minus (100 per height square) plus (35 for male/25 for female). A normal GFR is >90 mL/min, although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR <15 mL/min indicated kidney failure.
Timepoint [11] 0 0
Month 1, 3, 6, 9, 12
Secondary outcome [12] 0 0
Glomerular Filtration Rate (GFR) by The Cockcroft-Gault Equation - GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was measured directly or estimated using established formulas. GFR was calculated using Cockcroft-Gault equation. GFR by Cockcroft-Gault equation= body weight*(140 minus age in years) divided by (72*serum creatinine). For females value obtained was multiplied by 0.85. A normal GFR is >90 mL/min, although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR <15 mL/min indicated kidney failure.
Timepoint [12] 0 0
Month 1, 3, 6, 9, 12
Secondary outcome [13] 0 0
Glomerular Filtration Rate (GFR) by The Modification of Diet in Renal Disease (MDRD) Equation - GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was calculated using MDRD equation. GFR by MDRD equation = 170 * (serum creatinine)^(-0.999) * (age in years)^(-0.176) * (0.762 if female) * (1.18 if black) * (blood urea nitrogen concentration)^(-0.170) * (serum albumin concentration)^(0.318).A normal GFR is >90 mL/min/1.73 square meter (m^2), although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR <15 mL/min/1.73 m^2 indicated kidney failure.
Timepoint [13] 0 0
Month 1, 3, 6, 9, 12
Secondary outcome [14] 0 0
Glomerular Filtration Rate (GFR) by The Abbreviated Modification of Diet in Renal Disease (MDRD) Equation - GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was measured directly or estimated using established formulas. GFR was calculated using abbreviated MDRD equation. GFR by abbreviated MDRD equation= 186 * (serum creatinine)^(-1.154) * (age in years)^(-0.203) * (0.742 if female) * (1.210 if black). A normal GFR is >90 mL/min/1.73 m^2, although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR <15 mL/min/1.73 m^2 indicated kidney failure.
Timepoint [14] 0 0
Month 1, 3, 6, 9, 12
Secondary outcome [15] 0 0
Number of Participants With Clinically Significant Infections - Clinically significant infection was defined as the presence of documented infection confirmed by culture, biopsy, genomic, or serologic findings post-randomization and requiring hospitalization or parenteral anti-infective treatment, or otherwise deemed significant by the investigator.
Timepoint [15] 0 0
Baseline up to Month 12
Secondary outcome [16] 0 0
36-Item Short-Form Health Survey (SF-36) - SF-36: standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical and mental component scores. Total of 11 variables were analyzed (8 subscales,2 composite subscales and Question(Q) 2 "how would you rate your health in general now?"(range 1=better, 5=worst). The score for a section (except Q2) is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
Timepoint [16] 0 0
Baseline, Month 6, 12
Secondary outcome [17] 0 0
End-Stage Renal Disease Symptom Checklist Transplantation Module (ESRD-SCL) - ESRD-SCL:43-item disease specific self-administered questionnaire. Participants' rated question"At the moment,how much do you suffer?"for each item on 5 point scale,ranged (Ra) 0(not at all)to 4(extremely).Consisted of 6 subscales:cardiac and renal dysfunction;Ra 0-28,increased(In) growth of gum and hair;Ra 0-20,limited cognitive capacity;Ra 0-32,limited physical capacity;Ra 0 - 40,side effects (SEs) of corticosteroids;Ra 0-20,transplantation associated psychological distress(TAPD);Ra 0-32(higher scores=greater dysfunction for each subscale).Total score:0-172,higher scores=greater dysfunction.
Timepoint [17] 0 0
Baseline, Month 6, 12
Secondary outcome [18] 0 0
Severity of Dyspepsia Assessment (SODA) - SODA:17-item health scale, assessed participant-reported perceptions of dyspepsia;consists of 3 subscales:Pain Intensity (6-items to assess pain and intensity of abdominal [Ab] discomfort; Range (Ra):2-47, higher score= greater pain and Ab discomfort), Non-Pain Symptoms (7-items to assess severity and impact of non-pain symptoms:burping/belching,heartburn,bloating,flatulence,sour taste,nausea,and bad breath; Ra:7-35,higher scores = increased symptom severity and influence), and Satisfaction (4-items to assess degree of satisfaction with Ab discomfort; Ra:2-23,higher scores= more satisfaction).
Timepoint [18] 0 0
Baseline, Month 6, 12

Eligibility
Key inclusion criteria
- Recipient of a first-time kidney transplant

- Between the ages of 18 and 70 years, inclusive
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Recipient of any non-kidney transplant

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Pfizer Investigational Site - Camperdown
Recruitment hospital [2] 0 0
Pfizer Investigational Site - Westmead
Recruitment hospital [3] 0 0
Pfizer Investigational Site - Adelaide
Recruitment hospital [4] 0 0
Pfizer Investigational Site - Woodville
Recruitment hospital [5] 0 0
Pfizer Investigational Site - Clayton
Recruitment hospital [6] 0 0
Pfizer Investigational Site - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
5011 - Woodville
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
Belgium
State/province [19] 0 0
Anderlecht
Country [20] 0 0
Belgium
State/province [20] 0 0
Leuven
Country [21] 0 0
Brazil
State/province [21] 0 0
RS
Country [22] 0 0
Brazil
State/province [22] 0 0
SP
Country [23] 0 0
Canada
State/province [23] 0 0
Alberta
Country [24] 0 0
Czech Republic
State/province [24] 0 0
Praha 4
Country [25] 0 0
France
State/province [25] 0 0
Nantes
Country [26] 0 0
France
State/province [26] 0 0
Paris Cedex 15
Country [27] 0 0
France
State/province [27] 0 0
Toulouse Cedex 9
Country [28] 0 0
France
State/province [28] 0 0
Vandoeuvre Les Nancy
Country [29] 0 0
Germany
State/province [29] 0 0
Berlin
Country [30] 0 0
Germany
State/province [30] 0 0
Hamburg
Country [31] 0 0
Italy
State/province [31] 0 0
Bologna
Country [32] 0 0
Italy
State/province [32] 0 0
Roma
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Seoul
Country [34] 0 0
Netherlands
State/province [34] 0 0
Rotterdam
Country [35] 0 0
Norway
State/province [35] 0 0
Oslo
Country [36] 0 0
Poland
State/province [36] 0 0
Warszawa
Country [37] 0 0
Poland
State/province [37] 0 0
Wroclaw
Country [38] 0 0
Portugal
State/province [38] 0 0
Coimbra
Country [39] 0 0
Portugal
State/province [39] 0 0
Lisboa
Country [40] 0 0
Spain
State/province [40] 0 0
Barcelona

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
A new immunosuppressive drug, based on the inhibition of an important enzyme in the immune
system called JAK3, is being developed by Pfizer to prevent transplant rejection. In this
research study, a JAK3 inhibitor or cyclosporine will be given to new kidney transplant
patients for 12 months. Patients will be assigned to one of three treatment groups after
receiving a kidney transplant. Two of the treatment groups will receive 2 different dosing
regimens of the JAK3 inhibitor that will be taken by mouth. The third treatment group will be
a standard-of-care control arm. Patients will continue to take the assigned study medication
for 12 months as well as other standard transplant medications such as prednisone.
Trial website
https://clinicaltrials.gov/show/NCT00483756
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications