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

Kidney Transplantation Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00483756
• Other study ID #: A3921030
• Status: Completed
• Phase: Phase 2
• First received: June 6, 2007
• Last updated: February 8, 2013
• Start date: August 2007
• Est. completion date: April 2010

Study information

• Verified date: February 2013
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 338
• Est. completion date: April 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Drug:
• Cyclosporine
Standard of care
• CP-690,550
CP-690,550 15 mg BID for Months 1-6, then 10 mg BID for Months 7-12
• CP-690,550
CP-690,550 15 mg BID for Months 1-3, then 10 mg BID for Months 4-12

Locations

Country	Name	City	State
Australia	Pfizer Investigational Site	Adelaide	South Australia
Australia	Pfizer Investigational Site	Camperdown	New South Wales
Australia	Pfizer Investigational Site	Clayton	Victoria
Australia	Pfizer Investigational Site	Parkville	Victoria
Australia	Pfizer Investigational Site	Westmead	New South Wales
Australia	Pfizer Investigational Site	Woodville	South Australia
Belgium	Pfizer Investigational Site	Anderlecht
Belgium	Pfizer Investigational Site	Leuven
Brazil	Pfizer Investigational Site	Porto Alegre	RS
Brazil	Pfizer Investigational Site	Sao Paulo	SP
Brazil	Pfizer Investigational Site	Sao Paulo	SP
Canada	Pfizer Investigational Site	Edmonton	Alberta
Czech Republic	Pfizer Investigational Site	Praha 4
France	Pfizer Investigational Site	Nantes
France	Pfizer Investigational Site	Paris Cedex 15
France	Pfizer Investigational Site	Toulouse Cedex 9
France	Pfizer Investigational Site	Vandoeuvre Les Nancy
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Hamburg
Italy	Pfizer Investigational Site	Bologna
Italy	Pfizer Investigational Site	Roma
Korea, Republic of	Pfizer Investigational Site	Seoul
Korea, Republic of	Pfizer Investigational Site	Seoul
Korea, Republic of	Pfizer Investigational Site	Seoul
Netherlands	Pfizer Investigational Site	Rotterdam
Norway	Pfizer Investigational Site	Oslo
Poland	Pfizer Investigational Site	Warszawa
Poland	Pfizer Investigational Site	Wroclaw
Portugal	Pfizer Investigational Site	Coimbra
Portugal	Pfizer Investigational Site	Lisboa
Spain	Pfizer Investigational Site	Barcelona
Spain	Pfizer Investigational Site	Hospitalet de Llobregat	Barcelona
United States	Pfizer Investigational Site	Ann Arbor	Michigan
United States	Pfizer Investigational Site	Aurora	Colorado
United States	Pfizer Investigational Site	Baltimore	Maryland
United States	Pfizer Investigational Site	Boston	Massachusetts
United States	Pfizer Investigational Site	Chapel Hill	North Carolina
United States	Pfizer Investigational Site	Chapel Hill	North Carolina
United States	Pfizer Investigational Site	Chapel Hill	North Carolina
United States	Pfizer Investigational Site	Chapel Hill	North Carolina
United States	Pfizer Investigational Site	Charleston	South Carolina
United States	Pfizer Investigational Site	Chicago	Illinois
United States	Pfizer Investigational Site	Chicago	Illinois
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Detroit	Michigan
United States	Pfizer Investigational Site	Fort Worth	Texas
United States	Pfizer Investigational Site	Gainesville	Florida
United States	Pfizer Investigational Site	Gainsville	Florida
United States	Pfizer Investigational Site	Little Rock	Arkansas
United States	Pfizer Investigational Site	Livingston	New Jersey
United States	Pfizer Investigational Site	Los Angeles	California
United States	Pfizer Investigational Site	Los Angeles	California
United States	Pfizer Investigational Site	New Haven	Connecticut
United States	Pfizer Investigational Site	New Haven	Connecticut
United States	Pfizer Investigational Site	New York	New York
United States	Pfizer Investigational Site	Palo Alto	California
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania
United States	Pfizer Investigational Site	Portland	Oregon
United States	Pfizer Investigational Site	Rochester	Minnesota
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	San Francisco	California
United States	Pfizer Investigational Site	San Francisco	California
United States	Pfizer Investigational Site	Springfield	Massachusetts
United States	Pfizer Investigational Site	Springfield	Massachusetts
United States	Pfizer Investigational Site	St. Louis	Missouri
United States	Pfizer Investigational Site	Stanford	California
United States	Pfizer Investigational Site	Tampa	Florida
United States	Pfizer Investigational Site	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Czech Republic,  France,  Germany,  Italy,  Korea, Republic of,  Netherlands,  Norway,  Poland,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	Number of Participants Who Died		Month 6, 12	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No

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