Extension Study Of Stage 1 Subjects Of Study A3921009 For The Prevention Of Acute Rejection In Kidney Transplant Patient

NCT00263328 | Completed Phase 2 Results

• 1 other identifier: A3921021
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 27

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 study A3921009, kidney transplant patients were given a JAK inhibitor or tacrolimus for 6 months posttransplant. Patients who completed study A3921009 were offered the opportunity to participate in study A3921021 which will extend the evaluation of safety and efficacy of CP-690,550 versus tacrolimus through 8 years posttransplant. In treatment group 1 (control arm), subjects will continue to receive tacrolimus. In treatment groups 2 and 3, subjects will continue to receive CP-690,550. Per Amendment 4, the tacrolimus comparator arm will be discontinued.

Conditions

Kidney Transplantation

Keywords

immunosuppression; JAK3 inhibitor; kidney transplant; tofacitinib; Xeljanz; CP-690; 550; tacromilus; mycophenolate mofetil

Outcome Measures

Primary Outcomes (8)

• Calculated Glomerular Filtration Rate (GFR) Using 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 \[in milligrams per deciliter (mg/dL)\])\^(-0.999) \* (age in years)\^(-0.176) \* (0.762 if female) \* (1.18 if black) \* (blood urea nitrogen \[BUN\] concentration \[mg/dL\])\^(-0.170) \* (serum albumin concentration \[in grams per dL (g/dL)\])\^(0.318). A normal GFR is \>90 milliliters per minute per 1.73 square meters (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.

  Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)

• Serum Creatinine Levels

  Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)

• Kaplan-Meier Analysis of Percentage of Participants With Clinically Significant Infections by Visit

  Kaplan-Meier analysis of percentage of participants with clinically significant infections by time to first clinically significant infection within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier.

  Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96

• Kaplan-Meier Analysis of Percentage of Participants With New Onset Diabetes Mellitus, Definition 1 (NODM-1) by Visit

  Kaplan-Meier analysis of time to NODM-1 within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier. NODM-1 was defined as an event experienced by participants who were non-diabetic prior to transplantation and required treatment with oral hypoglycemic agents, anti-diabetic agents, and/or insulin for greater than or equal to (≥)30 days.

  Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96

• Percentage of Participants With Hypercholesterolemia

  Hypercholesterolemia was defined as cholesterol levels \>240 mg/dL or 6.2 mmol/L.

  Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96, and Follow-Up (Month 98)

• Percentage of Participants With Hypertriglyceridemia by Visit

  Hypertriglyceridemia was defined as triglyceride levels of \>200 mg/dL or 2.3 mmol/L.

  Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)

• Kaplan-Meier Analysis of Percentage of Participants With First Biopsy Proven Acute Rejection (BPAR) by Visit

  Kaplan-Meier analysis of percentage of participants with first BPAR by time to first BPAR within 96 months post-transplant. BPAR was defined as acute/active cellular rejection (Category 4 of the Banff Classification), based on the assessment of the renal allograft biopsy by a central, blinded pathologist. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier.

  Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96

• Kaplan-Meier Analysis of Percentage of Participants With Treatment Failure by Visit

  Kaplan-Meier analysis of percentage of participants with treatment failure by time to treatment failure within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier. Treatment failure was defined as the first occurrence of BPAR, death, graft loss or premature discontinuation of trial medication for any reason.

  Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96

Secondary Outcomes (44)

• Calculated GFR Using the Nankivell Equation (mL/Min)

  Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)

• Calculated GFR Using Cockcroft-Gault Equation (mL/Min)

  Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)

• Reciprocal of Serum Creatinine

  Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)

• Kaplan-Meier Analysis of Percentage of Participants With NODM, Definition 2 (NODM-2) by Visit

  Day 1 and Months 1, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, and 96

• Total Cholesterol Levels by Visit

  Months 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, and Follow-Up (Month 98)

Study Arms (3)

Treatment group 1

ACTIVE COMPARATOR

Standard of care

Drug: Tacrolimus

Treatment group 2

EXPERIMENTAL

Treatment group 2 also receives mycophenolate mofetil

Drug: CP-690,550

Treatment group 3

EXPERIMENTAL

Treatment group 3 does not receive mycophenolate mofetil

Drug: CP-690,550

Interventions

Tacrolimus DRUG

Standard of care

Treatment group 1

CP-690,550 DRUG

CP-690,550 5 mg BID

Treatment group 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Enrollment in Stage 1 of Study A3921009 and have completed 6-months of treatment with trial medications (CP-690,550 or tacrolimus)
• Recipient of a first-time kidney transplant

You may not qualify if:

• Subject with any untreated condition that may affect drug absorption (eg, gastrectomy or clinically significant diabetic gastroenteropathy).
• Subjects who are on the waiting list for a second kidney transplant or any non-renal organ transplants.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (27)

Multi Organ Transplant Center

Los Angeles, California, 90057, United States

Location

St. Vincent Medical Center

Los Angeles, California, 90057, United States

Location

Transplant Research Institute

Los Angeles, California, 90057, United States

Location

Stanford School of Medicine

Palo Alto, California, 94304, United States

Location

Balboa Institute of Transplantation

San Diego, California, 92123, United States

Location

California Institute of Renal Research

San Diego, California, 92123, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of California, San Francisco, Kidney Transplant Unit

San Francisco, California, 94143, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

University of Colorado Health Sciences Center Renal Clinical Trials Office

Aurora, Colorado, 80045, United States

Location

University of Colorado Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Northwestern University-Feinberg School of Medicine, Division of Organ Transplantation

Chicago, Illinois, 60611, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Jack J Dreyfus Clinic

New York, New York, 10021, United States

Location

Recanati/Miller Transplantation Institute

New York, New York, 10029, United States

Location

New York Presbyterian Hospital / Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Legacy Good Samaritan Hospital

Portland, Oregon, 97210, United States

Location

Legacy Transplant Services

Portland, Oregon, 97210, United States

Location

Northwest Renal Clinic

Portland, Oregon, 97210, United States

Location

Dallas Transplant Institute

Dallas, Texas, 75204, United States

Location

Annette C & Harold C Simmons Transplant Institute

Dallas, Texas, 75246, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Baylor All Saints Medical Center

Fort Worth, Texas, 76104, United States

Location

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Busque S, Leventhal J, Brennan DC, Steinberg S, Klintmalm G, Shah T, Mulgaonkar S, Bromberg JS, Vincenti F, Hariharan S, Slakey D, Peddi VR, Fisher RA, Lawendy N, Wang C, Chan G. Calcineurin-inhibitor-free immunosuppression based on the JAK inhibitor CP-690,550: a pilot study in de novo kidney allograft recipients. Am J Transplant. 2009 Aug;9(8):1936-45. doi: 10.1111/j.1600-6143.2009.02720.x.

  PMID: 19660021 DERIVED

Related Links

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

MeSH Terms

Interventions

Tacrolimus; tofacitinib

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2005
• First Posted: December 8, 2005
• Study Start: December 1, 2005
• Primary Completion: January 1, 2014
• Study Completion: June 1, 2014
• Last Updated: July 13, 2015
• Results First Posted: July 13, 2015

Record last verified: 2015-06

Locations

US (27)