Study of a JAK3 Inhibitor for the Prevention of Acute Rejection in Kidney Transplant Patients

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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Cyclosporine; Drug: CP-690,550; Drug: CP-690,550

• Study Type: Interventional
• Enrollment (Actual): 338
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Pfizer Investigational Site
    • Westmead, New South Wales, Australia, 2145
      • Pfizer Investigational Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Pfizer Investigational Site
    • Woodville, South Australia, Australia, 5011
      • Pfizer Investigational Site
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Pfizer Investigational Site
    • Parkville, Victoria, Australia, 3050
      • Pfizer Investigational Site
• Belgium
  • Anderlecht, Belgium, 1070
    • Pfizer Investigational Site
  • Leuven, Belgium, 3000
    • Pfizer Investigational Site
• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90020-090
      • Pfizer Investigational Site
  • SP
    • Sao Paulo, SP, Brazil, 04038-002
      • Pfizer Investigational Site
    • Sao Paulo, SP, Brazil, 04039-050
      • Pfizer Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Pfizer Investigational Site
• Czech Republic
  • Praha 4, Czech Republic, 140 21
    • Pfizer Investigational Site
• France
  • Nantes, France, 44093
    • Pfizer Investigational Site
  • Paris Cedex 15, France, 75743
    • Pfizer Investigational Site
  • Toulouse Cedex 9, France, 31059
    • Pfizer Investigational Site
  • Vandoeuvre Les Nancy, France, 54500
    • Pfizer Investigational Site
• Germany
  • Berlin, Germany, 10117
    • Pfizer Investigational Site
  • Hamburg, Germany, 20246
    • Pfizer Investigational Site
• Italy
  • Bologna, Italy, 40138
    • Pfizer Investigational Site
  • Roma, Italy, 00168
    • Pfizer Investigational Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 138-736
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 110-744
    • Pfizer Investigational Site
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Pfizer Investigational Site
• Norway
  • Oslo, Norway, 0027
    • Pfizer Investigational Site
• Poland
  • Warszawa, Poland, 02-006
    • Pfizer Investigational Site
  • Wroclaw, Poland, 50-417
    • Pfizer Investigational Site
• Portugal
  • Coimbra, Portugal, 3000-075
    • Pfizer Investigational Site
  • Lisboa, Portugal, 1069-166
    • Pfizer Investigational Site
• Spain
  • Barcelona, Spain, 08036
    • Pfizer Investigational Site
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Pfizer Investigational Site
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Pfizer Investigational Site
  • California
    • Los Angeles, California, United States, 90095
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90048
      • Pfizer Investigational Site
    • Palo Alto, California, United States, 94304
      • Pfizer Investigational Site
    • San Diego, California, United States, 92123
      • Pfizer Investigational Site
    • San Francisco, California, United States, 94115
      • Pfizer Investigational Site
    • San Francisco, California, United States, 94143
      • Pfizer Investigational Site
    • Stanford, California, United States, 94305
      • Pfizer Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Pfizer Investigational Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Pfizer Investigational Site
    • New Haven, Connecticut, United States, 06504
      • Pfizer Investigational Site
  • Florida
    • Gainesville, Florida, United States, 32610
      • Pfizer Investigational Site
    • Gainsville, Florida, United States, 32610
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33606
      • Pfizer Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Pfizer Investigational Site
    • Chicago, Illinois, United States, 60611
      • Pfizer Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Pfizer Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Pfizer Investigational Site
    • Springfield, Massachusetts, United States, 01107
      • Pfizer Investigational Site
    • Springfield, Massachusetts, United States, 01199
      • Pfizer Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Pfizer Investigational Site
    • Detroit, Michigan, United States, 48202
      • Pfizer Investigational Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Pfizer Investigational Site
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Pfizer Investigational Site
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Pfizer Investigational Site
  • New York
    • New York, New York, United States, 10029
      • Pfizer Investigational Site
    • Valhalla, New York, United States, 10595
      • Pfizer Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Pfizer Investigational Site
    • Chapel Hill, North Carolina, United States, 27599-7211
      • Pfizer Investigational Site
    • Chapel Hill, North Carolina, United States, 27599-7155
      • Pfizer Investigational Site
    • Chapel Hill, North Carolina, United States, 27599-7360
      • Pfizer Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Pfizer Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
      • Pfizer Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Pfizer Investigational Site
  • Texas
    • Dallas, Texas, United States, 75204
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75246
      • Pfizer Investigational Site
    • Fort Worth, Texas, United States, 76104
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Recipient of a first-time kidney transplant
• Between the ages of 18 and 70 years, inclusive

Exclusion Criteria:

• Recipient of any non-kidney transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Treatment Arm 1 will also receive standard of care medications	Drug: Cyclosporine; Standard of care
Experimental: 2; Treatment Arm 2 will also receive standard of care medications	Drug: CP-690,550; CP-690,550 15 mg BID for Months 1-6, then 10 mg BID for Months 7-12; Drug: CP-690,550; CP-690,550 15 mg BID for Months 1-3, then 10 mg BID for Months 4-12
Experimental: 3; Treatment Arm 3 will also receive standard of care medications	Drug: CP-690,550; CP-690,550 15 mg BID for Months 1-6, then 10 mg BID for Months 7-12; Drug: CP-690,550; CP-690,550 15 mg BID for Months 1-3, then 10 mg BID for Months 4-12

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline up to Month 6
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.	2, 3, 4, and 5 hrs post iohexol intravenous bolus at Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2, 3, 4, and 5 hrs post iohexol intravenous bolus at Month 6
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.	Month 12
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.	Baseline up to Month 12
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.	Month 6, 12
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.	Month 6, 12
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.	Month 6, 12
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.	Month 6, 12
Number of Participants Who Died		Month 6, 12
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.	Month 1, 3, 6, 12
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.	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
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.	Month 1, 3, 6, 9, 12
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.	Month 1, 3, 6, 9, 12
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.	Month 1, 3, 6, 9, 12
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.	Month 1, 3, 6, 9, 12
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.	Baseline up to Month 12
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).	Baseline, Month 6, 12
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.	Baseline, Month 6, 12
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).	Baseline, Month 6, 12

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: June 6, 2007
• First Submitted That Met QC Criteria: June 6, 2007
• First Posted (Estimate): June 7, 2007

Study Record Updates

• Last Update Posted (Estimate): March 14, 2013
• Last Update Submitted That Met QC Criteria: February 8, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: Immunosuppression; JAK3 inhibitor; kidney transplantation.
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Protein Kinase Inhibitors; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins; Tofacitinib
• Other Study ID Numbers: A3921030