A Study to Assess the Safety and Efficacy of Alefacept in Kidney Transplant Recipients

Kidney Transplantation Clinical Trial

Official title:

A Phase 2, Randomized, Open-Label, Parallel Group, Multi-Center Study to Assess the Safety and Efficacy of Alefacept in de Novo Kidney Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00543569
• Other study ID #: 0485-CL-U201
• Status: Completed
• Phase: Phase 2
• First received: October 11, 2007
• Last updated: November 6, 2015
• Start date: February 2008
• Est. completion date: February 2011

Study information

• Verified date: November 2015
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

A study to assess the safety and efficacy of Alefacept in de novo kidney transplant patients.

Description:

This is a 4 arm (all active) study to determine the safety and efficacy of Alefacept in de novo kidney transplant recipients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 323
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subject is anticipated to receive first oral dose of tacrolimus within 48 hours of transplant procedure

• Subject is a recipient of a de novo kidney transplant

• Subject is a recipient of a kidney from a non-human leukocyte antigen (HLA) identical related living donor, a non-related living donor, or a deceased donor

Exclusion Criteria:

• Subject has a screening (pre-operative)estimated cluster of differentiation (CD) 4+ T-cell count of < 250 cells/µL

• Subject will receive a kidney with an anticipated cold ischemia time (CIT) of > 30 hours

• Recipient has a positive T or B-cell cross match by investigational site's standard method of determination

• Subject will receive a kidney from a 50-65 year old deceased donor with one of the following:

• History of hypertension and a terminal serum creatinine > 1.5 mg/dL

• Cerebrovascular accident as cause of death and a terminal serum creatinine > 1.5 mg/dL

• History of hypertension and cerebrovascular accident as cause of death and a terminal serum creatinine > 1.5 mg/dL

Study Design

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

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Drug:
• Alefacept
Administered as a 7.5 mg intravenous bolus on day 0 (intraoperatively, prior to kidney revascularization) and Day 3; subsequently administered subcutaneously either weekly or every 2 weeks.
• tacrolimus
The initial dose of tacrolimus was administered orally within 48 hours post-transplant. Subsequent doses were to be adjusted to achieve target whole blood trough concentrations.
• basiliximab
Administered as a 20 mg bolus injection within 2 hours prior to transplantation and a 20 mg bolus injection on Day 3.
• mycophenolate mofetil
Administered at 750 mg twice per day orally or intravenously for patients enrolled under Amendment 6 or earlier and at 1000 mg twice per day orally or intravenously for patients enrolled under Amendment 7. The dose of MMF could be adjusted based on clinical symptoms.
• Corticosteroids
Corticosteroids were administered as a 500 to 1000 mg intravenous bolus on Day 0 and a 125 to 250 mg methylprednisone (or equivalent oral/intravenous corticosteroid dose) on Day 1. Oral prednisone was to be tapered per protocol.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Medical College of Georgia, Augusta	Augusta	Georgia
United States	University of Colorado Health Science Center	Aurora	Colorado
United States	University of Maryland Center	Baltimore	Maryland
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Buffalo General Hospital	Buffalo	New York
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Rush - Presbyterian - St. Lukes Medical Center	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	University Hospital of Cleveland	Cleveland	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Florida, Shands Hospital, Gainesville	Gainesville	Florida
United States	Pinnacle Health at Harrisburg	Harrisburg	Pennsylvania
United States	Methodist Hospital Research Institute of Houston	Houston	Texas
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	University of Kentucky	Lexington	Kentucky
United States	St. Barnabas Medical Center	Livingston	New Jersey
United States	Loma Linda University Medical Center	Loma Linda	California
United States	St. Vincent/National Institute of Transplantation	Los Angeles	California
United States	University of Southern California - University Hospital	Los Angeles	California
United States	University of Wisconsin Hospital	Madison	Wisconsin
United States	Methodist University Hospital - Memphis	Memphis	Tennessee
United States	Mt. Sinai School of Medicine	New York	New York
United States	New York Presbyterian Hospital - Cornell	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Legacy Transplant Services	Portland	Oregon
United States	Oregon Health & Science University	Portland	Oregon
United States	Virginia Commonwealth University School of Medicine	Richmond	Virginia
United States	UC Davis Medical Center	Sacramento	California
United States	University of Utah Medical Center	Salt Lake City	Utah
United States	California Institute of Renal Research/Sharp Memorial Hospital	San Diego	California
United States	UCSD	San Diego	California
United States	University of California - San Francisco	San Francisco	California
United States	University of Washington Medical Center	Seattle	Washington
United States	Westchester Medical Center	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Biopsy-confirmed Acute Rejection (BCAR) at Month 6 Assessed by Local Review	Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 2005 Banff criteria. All biopsies (T-cell and/or antibody mediated) of grade 1 or higher were considered a BCAR.; The Kaplan-Meier estimates at Day 182 was used for the analyses at 6 months. Lost to follow-up or patients with missing outcomes were censored at their last follow up visit.	6 months	No
Secondary	Patient Survival at Month 6 and Month 12	Patient survival is any participant who is known to be alive 6 months and 12 months after the skin closure date.; The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.	6 months and 12 months	No
Secondary	Graft Survival at Month 6 and Month 12	Graft survival was defined as any participant who was known to have a functioning graft (i.e., not graft loss) at 6 months and 12 months after the skin closure date. Graft loss was defined as patient death, retransplant, permanent return to dialysis (dialysis greater than 30 days) or transplant nephrectomy.; The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.	6 months and 12 months	No
Secondary	Percentage of Participants With BCAR at Month 12 Assessed by Local Review	Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 2005 Banff criteria. All biopsies (T-cell and/or antibody mediated) of grade 1 or higher were considered a BCAR.; The Kaplan-Meier estimates at Day 365 was used for the analyses at 12 months. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.	12 months	No
Secondary	Percentage of Participants With BCAR at Month 6 and 12 Assessed by Central Review	Rejection episodes were confirmed by biopsy by a central reviewer. Biopsies were graded according to the 2005 Banff criteria. All biopsies (T-cell and/or antibody mediated) of grade 1 or higher were considered a BCAR.; The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.	6 months and 12 months	No
Secondary	Percentage of Participants With T-cell Mediated BCAR at Month 6 and 12 Assessed by Local Review	Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 2005 Banff criteria. All biopsies of grade 1 or higher were considered a BCAR.; The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.	6 months and 12 months	No
Secondary	Percentage of Participants With T-cell Mediated BCAR at Month 6 and 12 Assessed by Central Review	Rejection episodes were confirmed by biopsy by the central reviewer. Biopsies were graded according to the 2005 Banff criteria. All biopsies of grade 1 or higher were considered a BCAR.; The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.	6 months and 12 months	No
Secondary	Change From Week 4 in Glomerular Filtration Rate Estimated by the MDRD Method at Month 6 and Month 12	The glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease (MDRD) method.	Week 4, Month 6 and Month 12	No
Secondary	Change From Week 4 in GFR by Iothalamate Clearance at Month 6	The glomerular filtration rate was measured directly using iothalamate clearance.	Week 4 and Month 6	No
Secondary	Change From Week 4 in Serum Creatinine at Month 6 and 12		Week 4 and Month 6 and 12	No
Secondary	Percentage of Participants With Efficacy Failure at 6 and 12 Months Assessed by Local Review	Efficacy failure is defined as death, graft failure (permanent return to dialysis [>30 days] or retransplant), BCAR according to local review, or lost to follow-up.	6 months and 12 months	No
Secondary	Percentage of Participants With Efficacy Failure at 6 and 12 Months Assessed by Central Review	Efficacy failure is defined as death, graft failure (permanent return to dialysis [>30 days] or retransplant), BCAR according to central review, or lost to follow-up.	6 months and 12 months	No
Secondary	Time to First BCAR Assessed by Local Review	The time to first BCAR (local review) was calculated as the first biopsy date in which the local reviewer confirmed an acute rejection minus the date of skin closure +1. Only participants with a BCAR are included in the analysis.	12 months	No
Secondary	Time to First BCAR Assessed by Central Review	The time to first BCAR (central review) was calculated as the first biopsy date in which the central reviewer confirmed an acute rejection minus the date of skin closure +1. Only participants with a BCAR are included in the analysis.	12 months	No
Secondary	Time to First T-cell Mediated BCAR Assessed by Local Review	The time to first T-cell mediated BCAR (local review) was calculated as the first biopsy date in which the local reviewer confirmed an acute rejection minus the date of skin closure +1.	12 months	No
Secondary	Time to First T-cell Mediated BCAR Assessed by Central Review	The time to first T-cell mediated BCAR (central review) was calculated as the first biopsy date in which the central reviewer confirmed an acute rejection minus the date of skin closure +1. Only participants with a T-cell mediated BCAR are included in the analysis.	12 months	No
Secondary	Maximum Grade of T-cell Mediated Rejection Assessed by Local Review	The grade of acute T-cell mediated rejection was classified as IA, IB, IIA, IIB and III according to Banff 2005 criteria. If a patient had more than 1 T-cell mediated rejection, the episode with the most severe grade was used in the analysis.; Grade IA: Cases with significant interstitial infiltration (> 25% of parenchyma affected) and foci of moderate tubulitis; Grade IB: Cases with significant interstitial infiltration (> 25% of parenchyma affected) and foci of severe tubulitis; Grade IIA: Cases with mild to moderate intimal arteritis; Grade IIB: Cases with severe intimal arteritis comprising >25% of the luminal area; Grade III: Cases with "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.	6 months and 12 months	No
Secondary	Maximum Grade of T-cell Mediated Rejection as Assessed by Central Review	The grade of acute T-cell mediated rejection was classified as IA, IB, IIA, IIB and III according to Banff 2005 criteria. If a patient had more than 1 T-cell mediated rejection, the episode with the most severe grade was used in the analysis.; Grade IA: Cases with significant interstitial infiltration (> 25% of parenchyma affected) and foci of moderate tubulitis; Grade IB: Cases with significant interstitial infiltration (> 25% of parenchyma affected) and foci of severe tubulitis; Grade IIA: Cases with mild to moderate intimal arteritis; Grade IIB: Cases with severe intimal arteritis comprising >25% of the luminal area; Grade III: Cases with "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.	6 months and 12 months	No
Secondary	Percentage of Participants With Clinically Treated Acute Rejection at Month 6 and Month 12	Patients who received immunosuppressive medications for the treatment of suspected or BCAR were considered to have a clinically-treated acute rejection.	6 months and 12 months	No
Secondary	Percentage of Participants With Anti-lymphocyte-treated Rejection at Months 6 and 12	Participants with histologically proved Banff Grade II or III rejection could receive anti-rejection therapy with anti-lymphocyte antibodies per institutional protocol.; The use of anti-lymphocyte antibody therapy at any time during a suspected or proven rejection episode for the treatment of acute rejection was considered an event.	6 months and 12 months	No
Secondary	Percentage of Participants With Multiple Rejection Episodes at Months 6 and 12	All participants were evaluated for the incidence of multiple rejection episodes (clinically treated and/or BCAR as assessed by the local reviewer) through 6 months and 12 months.	6 months and 12 months	No
Secondary	Percentage of Participants With Treatment Failure at Month 6 and 12	Treatment failure was defined as death, graft loss, BCAR (local review), lost to follow-up or early discontinuation of treatment regimen. The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.	6 months and 12 months	No
Secondary	Gastrointestinal Quality of Life Index Score Over Time	The impact of gastrointestinal (GI) symptoms on health-related quality of life was assessed using the Gastrointestinal Quality of Life Index (GIQLI) symptom severity score. The GIQLI is a 36-item self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past 2 weeks on a scale from 0 (all of the time) to 4 (never). Possible overall scores ranged from 0 to 4, with higher scores indicating a better quality of life according to the different symptomatic criteria.	Months 1, 3, 6, and 12	No
Secondary	Gastrointestinal Symptom Rating Scale Scores Over Time	The impact of gastrointestinal (GI) symptoms on health-related quality of life was assessed using the Gastrointestinal Symptom Rating Scale Scores (GSRS). The GSRS a 15-item self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort). Possible overall scores range from 1 to 7, with lower scores indicating a better quality of life with respect to gastrointestinal symptoms.	Months 1, 3, 6, and 12	No

External Links

•   Link to results on JAPIC