Belatacept in Liver Transplant Recipients

NCT00555321 | Terminated Phase 2 Results DMC

• 1 other identifier: IM103-045
• Study Type: interventional
• Target: 260
• Locations: 9 countries
• Sites: 42

Brief Summary

The purpose of this clinical research study is to evaluate the effects of belatacept, relative to tacrolimus, on the incidence of rejection, graft loss and death in subjects receiving a liver transplant

Conditions

Immunosuppression in Solid Organ Transplant

Outcome Measures

Primary Outcomes (6)

• Percentage of Participants Who Experienced at Least One Episode of Acute Rejection (AR), Graft Loss, or Death by 6 Months Post-transplant

  Any AR that was clinically suspected and biopsy proven (by central pathologist) was included in this triple composite end point. All biopsies for suspected AR were assessed by a blinded central histopathologist using Banff grading schema. Graft loss was defined as impairment of liver function to such a degree that the participant died or underwent re-transplantation. For 95% (confidence interval) CI within each group, normal approximation is used if N\>=5, otherwise exact method is used.

  At 6 months posttransplant

• Number of Participants Who Had Adverse Events (AEs), Death, Serious AEs (SAEs) or Were Discontinued Due to AEs (Includes Long Term Extension [LTE] Data)

  AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.

  Day 1 (randomization) to Week 104 + within 56 Days after the last infusion/dose, Deaths were monitored up to database lock (20-June-2011)

• Number of Participants Who Had AEs of Special Interest During the LTE

  AE of special interest included malignancies (including skin carcinomas), infections (viral, cytomegalovirus, herpes, fungal, and bacterial).

  Day 1 (randomization) through database lock (20-June-2011)

• Number of Participants With Marked Hematology Abnormalities During the LTE

  Low platelet count: \<50\*10\^9 c/µl; Low leukocytes: \<2.0\*10\^3 c/µl; Low lymphocytes (absolute): \<0.5\*10\^3 c/µl; Low neutrophils (absolute): \<1.0\*10\^3 c/µl.

  Every 4 weeks from Week 53 to Week 104.

• Number of Participants With Marked Liver and Kidney Function Abnormalities During the LTE

  ULN= upper limit of normal; Normal ranges are provided by the Central Laboratory and may vary according to sex and age. High alanine aminotransferase (ALT): \>5.0\*ULN U/L; High aspartate aminotransferase (AST): \>5.0\*ULN U/L; High direct bilirubin: \>3.0\*ULN mg/dL; High g-glutamyl transferase (GGT): \>5.0\*ULN U/L; High total bilirubin: \>3.0\*ULN mg/dL; High creatinine: \> 3.0\*ULN mg/dL

  Every 4 weeks from Week 53 to Week 104.

• Number of Participants With Marked Electrolytes, Protein and Metabolic Test Abnormalities During the LTE

  Low Serum Potassium: \<3.0 meq/L; High serum potassium:\>6.0 mEq/L; Low serum magnesium:\<0.8 mEq/L; Low serum sodium: \<130 mEq/L; High serum sodium: \>155 mEq/L; Low inorganic phosphorus: \<2.0 mg/dL; High uric acid: \>10 mg/dL

  Every 4 weeks from Week 53 to Week 104.

Secondary Outcomes (53)

• Percentage of Participants Surviving With Functional Graft: 12-month Treatment Phase

  At 6 and 12 months

• Percentage of Participants Surviving With Functional Graft by End of Study (Includes LTE Data)

  Day 1 (randomization) through database lock (20-June-2011)

• Percentage of Participants Who Experienced at Least One Episode of Acute Rejection, Graft Loss, or Death by 12 Months

  At 12 months posttransplant

• Percentage of Participants Who Experienced at Least One Episode of Acute Rejection, Graft Loss, or Death by End of Study (Includes LTE Data)

  Day 1 (randomization) through database lock (20-June-2011)

• Number of Participants Having Acute Rejections: 12-month Treatment Phase

  3 , 6, and 12 months

Study Arms (5)

Group 1: Basiliximab+Belatacept (MI) + MMF

EXPERIMENTAL

Drug: Basiliximab; Drug: Belatacept More Intensive (MI); Drug: Mycophenolate Mofetil (MMF)

Group 2: Belatacept (MI) + MMF

EXPERIMENTAL

Drug: Belatacept More Intensive (MI); Drug: Mycophenolate Mofetil (MMF)

Group 3: Belatacept Less Intensive (LI) + MMF

EXPERIMENTAL

Drug: Belatacept Less Intensive (LI); Drug: Mycophenolate Mofetil (MMF)

Group 4: Tacrolimus + MMF

OTHER

Other

Drug: Tacrolimus; Drug: Mycophenolate Mofetil (MMF)

Group 5: Tacrolimus

ACTIVE COMPARATOR

Drug: Tacrolimus

Interventions

Tacrolimus DRUG

Capsules, Oral, dosed to achieve 12 hour trough level of 6-12 ng/mL, twice daily, 52 weeks (Short Term \[ST\]), in accordance with local practice and the package insert, 4 years (Long-Term Extension \[LTE\])

Group 4: Tacrolimus + MMF; Group 5: Tacrolimus

Basiliximab DRUG

Intravenous (IV), 20 mg, Day1 and Day 5

Group 1: Basiliximab+Belatacept (MI) + MMF

Belatacept More Intensive (MI) DRUG

Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 6, 8, 10, 12, 16, 20, and 24. After 6 months (24 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), 5 mg/kg, every 4 weeks, 4 years (Long-term extension \[LTE\])

Group 1: Basiliximab+Belatacept (MI) + MMF; Group 2: Belatacept (MI) + MMF

Belatacept Less Intensive (LI) DRUG

Intravenous (IV), 10 mg/kg on Days 1, 3 and 5, and at Weeks 2, 4, 8 and 12. After 3 months (12 weeks) 5 mg/kg, every 4 weeks, 52 weeks (Short term \[ST\]), 5 mg/kg, every 4 weeks, 4 years (Long-Term Extension(LTE)

Group 3: Belatacept Less Intensive (LI) + MMF

Mycophenolate Mofetil (MMF) DRUG

Intravenous (IV)/Capsules, IV/Oral, 1-2g/day, 52 weeks (Short term \[ST\]), ≤ 1 g/day, 4 years (Long-term extension \[LTE\])

Group 1: Basiliximab+Belatacept (MI) + MMF; Group 2: Belatacept (MI) + MMF; Group 3: Belatacept Less Intensive (LI) + MMF; Group 4: Tacrolimus + MMF

Eligibility Criteria

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

You may qualify if:

• First time recipient of deceased donor liver transplant
• Age 18-70
• Hepatitis C virus (HCV) positive recipients
• For Long-term extension study-Subjects who have completed one year of study treatment (through Week 52)
• Medical History and Concurrent Diseases
• Subjects who have received 2 or more consecutive weeks of dialysis 1 month prior to enrollment OR anticipated to have prolonged dialysis post-transplantation
• Subjects with known intrinsic renal disease (e.g., a urine protein/ creatinine ratio \> 150 mg/g or the presence of an abnormal number of red blood cells (RBCs) or granular casts in the urine) AND calculated GFR \< 40 ml/min/1.73 m\^2 body surface area (BSA) (abbreviated Modification of Diet in Renal Disease \[MDRD\]). Subjects must have a calculated GFR assessment within 1 month prior to enrollment.
• Subjects with known HIV
• Subjects with any prior or concurrent solid organ (e.g., heart, kidney, pancreas) or cell (e.g., islet, bone marrow) transplant or subjects deemed likely to have a second solid organ or cell transplant (e.g., islet, bone marrow) within the next 3 years.
• Subjects with a history of cancer within the last 5 years
• Allergies and Adverse Drug Reactions
• a) Hypersensitivity to any medications that will be used in the protocol
• Prohibited Treatments and/or Therapies
• Subjects receiving immunosuppressive agent(s) (e.g., methotrexate, abatacept, infliximab, etanercept, chemotherapy, etc.) within the past 6 months for other indications such as an autoimmune disease
• Subjects who received maintenance corticosteroids at a dose of \> 5 mg/day of prednisone (or equivalent) for at least 7 consecutive days within the prior year for an underlying chronic inflammatory or autoimmune disease

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (42)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Usc University Hospital

Los Angeles, California, 90033, United States

Location

University Of California San Francisco Medical Center

San Francisco, California, 94143, United States

Location

Mayo Clinic Transplant Department

Jacksonville, Florida, 32224, United States

Location

Lifelink Healthcare Institute

Tampa, Florida, 33606, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Northwestern University Feinberg School Of Medicine

Chicago, Illinois, 60611, United States

Location

Tulane Center For Abdominal Transplant

New Orleans, Louisiana, 70112, United States

Location

Henry Ford Hospital

Detriot, Michigan, 48202, United States

Location

University Of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University School Of Medicine

St Louis, Missouri, 63110, United States

Location

Nyu School Of Medicine

New York, New York, 10016, United States

Location

Westchester Medical Center

Valhalla, New York, 10595, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Univ. Of Cin. Coll. Of Med.

Cincinnati, Ohio, 45267, United States

Location

Integris-Baptist Medical Ctr.

Oklahoma City, Oklahoma, 73112, United States

Location

Hospital Of The University Of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Local Institution

Ciudad de Buenos Aires, Buenos Aires, C1181ACH, Argentina

Location

Local Institution

Vienna, 1090, Austria

Location

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Curitiba, Paraná, 80060, Brazil

Location

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Rio de Janeiro, Rio de Janeiro, 21041, Brazil

Location

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

Location

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Edmonton, Alberta, T6G 2B7, Canada

Location

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Toronto, Ontario, M5G 2N2, Canada

Location

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Clichy, 92118, France

Location

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Lyon, 69437, France

Location

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Montpellier, 34295, France

Location

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Paris, 75014, France

Location

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Toulouse, 31059, France

Location

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Villejuif, 94800, France

Location

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Berlin, 13353, Germany

Location

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Hamburg, 20246, Germany

Location

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Hanover, 30625, Germany

Location

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Heidelberg, 69120, Germany

Location

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Tübingen, 72076, Germany

Location

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Bergamo, 24128, Italy

Location

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Padua, 35128, Italy

Location

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Pisa, 56124, Italy

Location

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Roma, 00168, Italy

Location

Local Institution

Barcelona, 08036, Spain

Location

Related Publications (1)

• Klintmalm GB, Feng S, Lake JR, Vargas HE, Wekerle T, Agnes S, Brown KA, Nashan B, Rostaing L, Meadows-Shropshire S, Agarwal M, Harler MB, Garcia-Valdecasas JC. Belatacept-based immunosuppression in de novo liver transplant recipients: 1-year experience from a phase II randomized study. Am J Transplant. 2014 Aug;14(8):1817-27. doi: 10.1111/ajt.12810.

  PMID: 25041339 DERIVED

MeSH Terms

Interventions

Tacrolimus; Basiliximab; Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: BMS 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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2007
• First Posted: November 8, 2007
• Study Start: January 1, 2008
• Primary Completion: March 1, 2010
• Study Completion: June 1, 2011
• Last Updated: October 18, 2012
• Results First Posted: October 18, 2012

Record last verified: 2012-09

Locations

ES (1); CA (2); US (19); FR (6); DE (5); IT (4); AR (1); AU (1); BR (3)