Extension Study Of Subjects From Study A3921030 For The Prevention Of Acute Rejection In Kidney Transplant Patients

NCT00658359 | Completed Phase 2 Results DMC

• 2 other identifiers: A39210502008-002345-23
• Study Type: interventional
• Target: 178
• Locations: 15 countries
• Sites: 65

Brief Summary

This is a study that will follow transplant patients from Study A3921030 to monitor for long term safety, tolerability and efficacy for 5 additional years, except in Portugal where the study will follow transplant patients through Month 36 posttransplant. Patients will continue their study medications that were previously assigned.

Conditions

Kidney Transplantation

Keywords

Immunosuppression; JAK inhibitor; kidney transplantation

Outcome Measures

Primary Outcomes (6)

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

  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. The 'Number' and 'Other Confidence Interval Level' columns represent cumulative proportions and 60% confidence intervals (CIs) as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits.

  Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

• Percentage of Participants With Malignancies

  All treatment-emergent malignancies in Study A3921050 were included as collected on the Malignancy Case Report Form page.

  Months 12 through 72.

• Least Squares Means of Measured Glomerular Filtration Rate (GFR) (Iohexol Serum Clearance in Milliliters Per Minute [mL/Min])

  Glomerular filtration rate (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 (IV) bolus over 5 minutes immediately after morning dosing of Tofacitinib or CsA on day of GFR evaluation. Blood samples for iohexol (3 millilitres \[mL\] each to provide a minimum of 1 mL serum) were collected into appropriately labeled tubes containing no additives at 120, 180, 240, and 300 minutes after the end of the iohexol IV bolus. A normal GFR is greater than (\>) 90 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.

  Month 36

• Percentage of Participants With Progression of Chronic Allograft Lesions at Month 36

  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 36 Banff-CS greater than the implantation biopsy score indicated progression of lesions.

  Month 36

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

  BPAR was category acute rejection as interpreted by the central blinded pathologist according to the Banff 97 working classification. The 'Number' and 'Other Confidence Interval Level' columns represent cumulative proportions and 60% confidence intervals (CIs) as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits.

  Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

• Kaplan-Meier Analysis of Percentage of Participants With Treated Clinical Acute Rejection by Visit

  Treated clinical acute rejection was defined as an acute rejection episode that was diagnosed based on local biopsy readout and received anti-rejection treatment. The 'Number' and 'Other Confidence Interval Level' columns represent cumulative proportions and 60% confidence intervals (CIs) as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits.

  Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

Secondary Outcomes (22)

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

  Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

• Kaplan-Meier Analysis of Percentage of Participants With Combined Banff Rejection by Visit

  Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

• Kaplan-Meier Analysis of Percent of Participants With Graft Survival With Death Censored by Visit

  Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

• Kaplan-Meier Analysis of Percentage of Participants Surviving by Visit

  Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

• Percentage of Participants Discontinuing From the Study

  Months 12 through 72.

Study Arms (3)

Treatment Arm 1

ACTIVE COMPARATOR

Treatment Arm 1 will also receive standard of care medications

Drug: Cyclosporine

Treatment Arm 2

EXPERIMENTAL

Treatment Arm 2 will also receive standard of care medications

Drug: CP-690,550

Treatment Arm 3

EXPERIMENTAL

Treatment Arm 3 will also receive standard of care medications

Drug: CP-690,550

Interventions

Cyclosporine DRUG

Standard of care

Treatment Arm 1

CP-690,550 DRUG

CP-690,550 tablets dosed BID Months 12-72

Treatment Arm 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:

• Subjects who successfully completed Study A3921030

You may not qualify if:

• Subjects who are on the waiting list for a second kidney transplant or any non-renal organ transplants

Sponsors & Collaborators

• Pfizer: lead

Study Sites (65)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Cedars-Sinai MedicalCenter

Los Angeles, California, 90048, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Stanford School of Medicine

Palo Alto, California, 94304, United States

Location

Stanford University Medical Center

Palo Alto, California, 94305, 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 - Pacific Campus

San Francisco, California, 94115, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

UCSF Medical Center - Long Hospital

San Francisco, California, 94143, United States

Location

USCF Medical Center - Connie Frank Transplant Center

San Francisco, California, 94143, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Yale-New Haven Hospital

New Haven, Connecticut, 06504, United States

Location

Yale Physicians Building

New Haven, Connecticut, 06510, United States

Location

University Of Florida

Gainesville, Florida, 32610, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

NUCATS's Clinical Research Unit

Chicago, Illinois, 60611, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Hurley Medical Center

Flint, Michigan, 48503, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Investigational Drug Services (IDS) / UNC Healthcare

Chapel Hill, North Carolina, 27514, United States

Location

Transplant Clinic/UNC Heathcare

Chapel Hill, North Carolina, 27514, United States

Location

UNC Department of Surgery, Clinical Trials Consortium

Chapel Hill, North Carolina, 27599-7211, United States

Location

UNC Department of Surgery/Abdominal Transplant Division

Chapel Hill, North Carolina, 27599-7211, United States

Location

Division of Pharmacotherapy, School of Pharmacy, University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7360, United States

Location

University of North Carolina, Department of Medicine/Nephrology

Chapel Hill, North Carolina, 27599, United States

Location

Drexel University College of Medicine - Hahnemann University Hospital

Philadelphia, Pennsylvania, 19102, United States

Location

Hahnemann University Hospital

Philadelphia, Pennsylvania, 19102, United States

Location

Medical University of South Carolina, Department of Transplantation Surgery

Charleston, South Carolina, 29425, United States

Location

Nephrology Clinic

Charleston, South Carolina, 29425, United States

Location

Dallas Transplant Institute

Dallas, Texas, 75204, United States

Location

Annette C. and Harold C. Simmons Transplant Institute at Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Westmead Hospital, Department of Renal Medicine

Westmead, New South Wales, 2145, Australia

Location

Central Northern Adelaide Renal and Transplantation Service

Adelaide, South Australia, 5000, Australia

Location

The Queen Elizabeth Hospital

Woodville, South Australia, 5011, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Hopital Erasme

Anderlecht, Brussels Capital, 1070, Belgium

Location

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Irmandade Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

Location

Hospital do Rim e Hipertensao

São Paulo, São Paulo, 04038-002, Brazil

Location

Ambulatorio Pos Transplante do Hospital do Rim a Hipertensao

São Paulo, São Paulo, 04039-033, Brazil

Location

Hospital do Rim e Hipertensao

São Paulo, 04038-002, Brazil

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Institut Klinicke a Experimentalni Mediciny

Praha 4 Krc, 140 21, Czechia

Location

Hopital Necker

Paris, 75743, France

Location

CHRU de Nancy-Brabois - Service de Nephrologie

Vandœuvre-lès-Nancy, 54500, France

Location

Charite - Universitatsmedizin Berlin

Berlin, 10117, Germany

Location

Istituto di Clinica Chirurgica, Universita Cattolica del Sacro Cuore

Roma, RM, 00168, Italy

Location

Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola Malpighi

Bologna, 40138, Italy

Location

Erasmus Medisch Centrum

Rotterdam, 3015 GD, Netherlands

Location

Oslo universitetssykehus HF- Rikshospitalet

Oslo, 0372, Norway

Location

Akademicki Szpital Kliniczny im. J. Mikulicza - Radeckiego we Wroclawiu

Wroclaw, 50-556, Poland

Location

Hospitais da Universidade de Coimbra, EPE

Coimbra, 3000-075, Portugal

Location

Hospital Curry Cabral

Lisbon, 1069-166, Portugal

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Department of Surgery, Yonsei University College of Medicine Severance Hospital

Seoul, 120-752, South Korea

Location

Asan Medical Center, Department of Surgery

Seoul, 138-736, South Korea

Location

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Related Links

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

MeSH Terms

Interventions

Cyclosporine; tofacitinib

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

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: LTE60
• 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: April 9, 2008
• First Posted: April 15, 2008
• Study Start: August 1, 2008
• Primary Completion: March 1, 2015
• Study Completion: June 1, 2015
• Last Updated: February 23, 2018
• Results First Posted: February 23, 2018

Record last verified: 2018-02

Locations

DE (1); FR (2); AU (5); CA (1); BE (2); KR (3); PL (1); NL (1); ES (2); PT (2); NO (1); US (37); BR (4); IT (2); CZ (1)