Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression (BENEFIT)

NCT00256750 | Completed Phase 3 Results DMC

• 1 other identifier: IM103-008
• Study Type: interventional
• Target: 738
• Locations: 20 countries
• Sites: 101

Brief Summary

The purpose of this study is to learn if Belatacept can provide protection from organ rejection following kidney transplantation while avoiding some of the toxic effects of standard immunosuppressive medications such as kidney damage. Effects on kidney function and patient survival as well as drug safety will also be studied.

Conditions

Kidney Transplantation; Chronic Kidney Failure

Outcome Measures

Primary Outcomes (3)

• Percent of Participants Surviving With a Functioning Graft by Month 12

  Graft loss was defined as either functional loss or physical loss (nephrectomy). Functional loss was defined as a sustained level of serum creatinine (SCr) ≥ 6.0 milligrams per deciliter (mg/dL) or 530 micromolar per liter (μmol/L) as determined by the central laboratory for ≥ 4 weeks or ≥ 56 consecutive days of dialysis or impairment of renal function to such a degree that the participant underwent retransplant.

  Day 1 to Month 12

• Percent of Participants With a Composite of Measured Glomerular Filtration Rate (mGFR) Less Than 60 mL/Min/1.73 m^2 at Month 12 or With a Decrease in mGFR Greater Than or Equal to 10 mL/Min/1.73m^2 From Month 3 to Month 12

  Measured glomerular filtration rate (mGFR) is the direct measurement of renal function and was assessed by measurement of the clearance of a true glomerular filtration marker (non-radiolabeled iothalamate) using a validated procedure. A GFR of 60 mL/min/1.73 m\^2 was used as the approximate equal of the threshold values of serum creatinine (SCr) of 1.5 mg/dL. A change in GFR of at least 10 mL/min/1.73 m\^2 was used as the approximate change in SCr of at least 0.3 mg/dL. The change component of the composite renal endpoint was assessed from Month 3 to Month 12, since post-transplant renal function is largely stable by Month 3.

  Month 12; Month 3 to Month 12

• Percent of Participants Experiencing Acute Rejection (AR) Post-transplant by Month 12

  Acute rejection was defined as a clinico-pathological event requiring clinical evidence and biopsy confirmation. Clinical evidence was defined if either a or b was satisfied: a: an unexplained rise of serum creatinine ≥ 25% from baseline creatinine; b: an unexplained decreased urine output; or fever and graft tenderness; or a serum creatinine that remains elevated within 14 days post-transplantation and clinical suspicion of acute rejection exists. Allograft biopsies were evaluated by a blinded central independent pathologist using Banff 97 working classification of kidney transplant pathology. Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. AR was defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection. Only the episode with the highest Banff grade for each participant was counted.

  Day 1 to Month 12

Secondary Outcomes (40)

• Mean Value of the Measured Glomerular Filtration Rate (mGFR)

  Months 3, 12, 24

• Percent of Participants With Prevalence of Chronic Allograft Nephropathy (CAN) at Month 12

  Month 12

• Number of Participants With Serious Adverse Events, Death, Discontinuation Due to Adverse Events by Month 84

  Randomization to Month 84

• Number of Participants With Adverse Events of Special Interest by Month 84

  Randomization to Month 84

• Mean Blood Pressure at Month 84

  Month 84

Study Arms (3)

Cyclosporine (CsA)

ACTIVE COMPARATOR

Drug: Cyclosporine (CsA)

Belatacept LI (less intensive)

EXPERIMENTAL

Drug: Belatacept LI (less intensive)

Belatacept MI (more intensive)

EXPERIMENTAL

Drug: Belatacept MI (more intensive)

Interventions

Cyclosporine (CsA) DRUG

tablet, oral, 1st month target: 150-300 ng/mL, after 1st month target: 100-250 ng/mL, daily, 36 months (ST), 100-250 ng/mL, daily, 24 months (LT)

Cyclosporine (CsA)

Belatacept LI (less intensive) DRUG

solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)

Belatacept LI (less intensive)

Belatacept MI (more intensive) DRUG

solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months (ST), 5 mg/kg every 4 weeks, q 4 weeks, 24 months (LT)

Belatacept MI (more intensive)

Eligibility Criteria

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

You may qualify if:

• The subject is a recipient of a living donor or deceased donor kidney transplant.
• Male or Female, 18 or older

You may not qualify if:

• First time recipient, PRA \>- 50% or for retransplantation PRA \>- 30%.
• If retransplantation, previous graft loss cannot be due to acute rejection.
• Positive cross match.
• Subject receiving extended criteria donor (ECD) organ
• For Long-term extension study-Subjects who have completed three years of study treatment (through Week 156)

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (105)

University Of Alabama At Birmingham

Birmingham, Alabama, 35294, United States

Location

Loma Linda University Medical Center-Transplantation Institu

Loma Linda, California, 92354, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

California Institute Of Renal Research

San Diego, California, 92123, United States

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University Of California San Francisco Medical Center

San Francisco, California, 94143, United States

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University Of Colorado Health Sciences Center

Aurora, Colorado, 80045, United States

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Yale University School Of Medicine-Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

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Piedmont Hospital

Atlanta, Georgia, 30309, United States

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Emory University Hospital

Atlanta, Georgia, 30322, United States

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Medical College Of Georgia

Augusta, Georgia, 30912, United States

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University Of Chicago Hospitals

Chicago, Illinois, 60637, United States

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University Of Iowa Hospitals And Clinics

Iowa City, Indiana, 52242, United States

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University Of Kentucky

Lexington, Kentucky, 40536, United States

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Maine Tranplant Program

Portland, Maine, 04102, United States

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Western New England Renal & Transplant Associates, Pc

Springfield, Massachusetts, 01107, United States

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Henry Ford Hospital, Transplant Institute

Detriot, Michigan, 48202, United States

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University Of Minnesota

Minneapolis, Minnesota, 55455, United States

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Washington University School Of Medicine

St Louis, Missouri, 63110, United States

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Recanati/Miller Transplantation Institute

New York, New York, 10029, United States

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Columbia University College Of Physicians & Surgeons

New York, New York, 10032, United States

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University Of Rochester Medical Center

Rochester, New York, 14642, United States

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University Of North Carolina At Chapel Hill

Chapel Hill, North Carolina, 27599, United States

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Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Div Of Multi-Organ Trans, Hepato-Biliary-Pancreatic Surgery

Philadelphia, Pennsylvania, 19102, United States

Location

Musc

Charleston, South Carolina, 29425, United States

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Vanderbilt University Medical Center

Nashville, Tennessee, 27232, United States

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Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Fletcher Allen Health Care

Burlington, Vermont, 05401, United States

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Inova Transplant Center

Fairfax, Virginia, 22031, United States

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Swedish Medical Center

Seattle, Washington, 98104, United States

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Sacred Heart Medical Ctr Providence Medical Research Ctr

Spokane, Washington, 99204, United States

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University Of Wisconsin

Madison, Wisconsin, 53792, United States

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Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, 53226, United States

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Local Institution

Buenos Aires, Buenos Aires, C1155APP, Argentina

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Capital Federal, Buenos Aires, C1425APQ, Argentina

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La Plata, Buenos Aires, 1900, Argentina

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Cordoba, Crd, Córdoba Province, X5016KEH, Argentina

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Rosario, Santa Fe Province, 2000, Argentina

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Santa Fe, Santa Fe Province, S3000EPV, Argentina

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Camperdown, New South Wales, 2050, Australia

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Westmead, New South Wales, 2145, Australia

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Adelaide, South Australia, 5000, Australia

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Parkville, Victoria, 3052, Australia

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Innsbuck, 6020, Austria

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Vienna, 1090, Austria

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Rio de Janeiro / Rj, Rio de Janeiro, 21041, Brazil

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Porto Alegre, Rio Grande do Sul, 90035, Brazil

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Porto Alegre/rs, Rio Grande do Sul, 90035, Brazil

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Campinas, São Paulo, 13033, Brazil

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Sao Paulo/sp, São Paulo, 04038, Brazil

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São Paulo, São Paulo, 05403, Brazil

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Edmonton, Alberta, T6G 2S2, Canada

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Halifax, Nova Scotia, B3H 2Y9, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Montreal, Quebec, H2L 2W5, Canada

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Montreal, Quebec, H3A 1A1, Canada

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Saskatoon, Saskatchewan, S7M 0Z9, Canada

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Prague, 140 21, Czechia

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Bordeaux, 33076, France

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Brest, 29609, France

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Créteil, 94000, France

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Grenoble, 38043, France

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Nantes, 44093, France

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Paris, 75015, France

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Toulouse, 31054, France

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Berlin, 13353, Germany

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Erlangen, 91054, Germany

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Essen, 45122, Germany

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Hanover, 30625, Germany

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Szeged, H-6720, Hungary

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Gujarat, Ahmedabad, 380016, India

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Chandigarh, Chandigarh, 160012, India

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Ahmedabad, Gujarat, 380052, India

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Nadiād, Gujarat, 387001, India

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Kochi, Kerala, 682304, India

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Mumbai, Maharashtra, 400 026, India

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Mumbai, Maharashtra, 400016, India

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Chennai, 600 006, India

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Lucknow, 226000, India

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New Delhi, 110076, India

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Petah Tikva, 49100, Israel

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Milan, 20162, Italy

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Padua, 35128, Italy

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Roma, 00168, Italy

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Aguascalientes, Aguascalientes, 20000, Mexico

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Distrito Federal, Mexico City, 14080, Mexico

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Mexico City, Mexico City, 14080, Mexico

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Cuernavaca, Morelos, 62448, Mexico

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Monterrey, Nuevo León, 64460, Mexico

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San Luis Potosí City, San Luis Potosí, 78240, Mexico

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Poznan, 60-479, Poland

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Szczecin, 70-111, Poland

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Observatory, Cape Town, 7925, South Africa

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Pretoria, Gauteng, 0002, South Africa

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Durban, KwaZulu-Natal, 4001, South Africa

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Barcelona, 08907, Spain

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Madrid, 28040, Spain

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Málaga, 29010, Spain

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Gothenburg, SE-413 45, Sweden

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Bern, 3010, Switzerland

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Zurich, 8091, Switzerland

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Antalya, 07059, Turkey (Türkiye)

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Related Publications (3)

• Vincenti F, Rostaing L, Grinyo J, Rice K, Steinberg S, Gaite L, Moal MC, Mondragon-Ramirez GA, Kothari J, Polinsky MS, Meier-Kriesche HU, Munier S, Larsen CP. Belatacept and Long-Term Outcomes in Kidney Transplantation. N Engl J Med. 2016 Jan 28;374(4):333-43. doi: 10.1056/NEJMoa1506027.

  PMID: 26816011 DERIVED

• Dobbels F, Wong S, Min Y, Sam J, Kalsekar A. Beneficial effect of belatacept on health-related quality of life and perceived side effects: results from the BENEFIT and BENEFIT-EXT trials. Transplantation. 2014 Nov 15;98(9):960-8. doi: 10.1097/TP.0000000000000159.

  PMID: 24831918 DERIVED

• Vincenti F, Larsen CP, Alberu J, Bresnahan B, Garcia VD, Kothari J, Lang P, Urrea EM, Massari P, Mondragon-Ramirez G, Reyes-Acevedo R, Rice K, Rostaing L, Steinberg S, Xing J, Agarwal M, Harler MB, Charpentier B. Three-year outcomes from BENEFIT, a randomized, active-controlled, parallel-group study in adult kidney transplant recipients. Am J Transplant. 2012 Jan;12(1):210-7. doi: 10.1111/j.1600-6143.2011.03785.x. Epub 2011 Oct 12.

  PMID: 21992533 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Cyclosporine

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2005
• First Posted: November 22, 2005
• Study Start: March 1, 2005
• Primary Completion: June 1, 2008
• Study Completion: April 1, 2015
• Last Updated: August 19, 2016
• Results First Posted: August 19, 2016

Record last verified: 2016-07

Locations

AU (2); CZ (1); IL (1); SE (1); US (34); CH (2); BR (6); HU (1); CA (6); IN (10); PL (2); ES (3); BE (2); AR (6); IT (3); TU (1); FR (7); ME (6); ZA (3); DE (4)