A Study of Belimumab in the Prevention of Kidney Transplant Rejection

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01536379
First received: February 16, 2012
Last updated: September 18, 2014
Last verified: September 2014
  Purpose

Kidney transplantation is the best treatment for many patients with kidney failure. Sometimes a transplanted kidney is rejected by the patient's immune system. Many types of immune system cells, including B cells, are active in rejection. B cells produce antibodies against anything the body sees as non-self, like germs or a transplanted kidney. Most medicines that help prevent transplant rejection affect cells other than B cells. Belimumab is a medication used to treat a disease called lupus. Belimumab slows development of antibody-producing B cells. This study will test whether belimumab works on parts of the immune system that cause rejection. Twenty to thirty adults getting a kidney transplant will be in this study. Like flipping a coin, a computer will randomly assign half to be given belimumab and half to be given placebo (a fake medicine). Patients and doctors will not know which medicine was assigned until the study is over. A total of 7 doses of study medicine will be given through a vein. One dose will be given during transplant surgery, and the other 6 will be given 2, 4, 8, 12, 16 and 20 weeks after transplant surgery. Usual transplant medicines will also be given. After all of the doses have been given, patients will be watched and tested at 24, 36, and 52 weeks after the transplant surgery. Blood samples will be tested to see what study medicines do to the immune system in transplant patients. If patients get a kidney biopsy, the samples will be tested to see if belimumab had any effect. Patients will be asked many questions to see if they are having any side effects. The study will be done at Addenbrooke's Hospital in Cambridge and Guys &St Thomas Hospital in London, United Kingdom. A pharmaceutical company, GlaxoSmithKline, is funding the study.


Condition Intervention Phase
Transplantation, Organ
Drug: Belimumab
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: BEL114424: A Phase 2 Pilot, Multicentered, Randomised, Double Blind, Placebo-Controlled Study to Evaluate the Potential for Efficacy and the Safety of Belimumab Plus Standard of Care Versus Placebo Plus Standard of Care in the Prevention of Allograft Rejection in Adult Subjects After Renal Transplantation

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change from baseline in naïve B cells from baseline to Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Change from Baseline in naïve B cells will be calculated as the value at Week 24 minus the value at Baseline

  • Incidence and occurrence of AE and SAE [ Time Frame: Assessed Up to 1 year ] [ Designated as safety issue: No ]
    AEs and SAEs will be collected from the screening until the follow-up visit

  • Incidence and severity of infections [ Time Frame: Assessed Up to 1 year ] [ Designated as safety issue: No ]
  • Change from baseline in Vital signs [ Time Frame: Assessed Up to 1 year ] [ Designated as safety issue: No ]
    Change from baseline and number of subjects outside the normal range for blood pressure, heart rate, and temperature. Change from Baseline will be calculated as the value on Day 365 minus the value at Baseline

  • Change from baseline in clinical laboratory parameters [ Time Frame: Assessed Up to 1 year ] [ Designated as safety issue: No ]
    Change from baseline and number of subjects outside the normal range for clinical chemistry and hematology parameters, with particular attention to white blood cell count and immunoglobulin levels. Change from Baseline will be calculated as the value on Day 365 minus the value at Baseline


Secondary Outcome Measures:
  • Percent change from baseline in memory B cells [ Time Frame: Assessed At Week 24 ] [ Designated as safety issue: No ]
    Percent Change from Baseline in memory B cells will be calculated as the value at Week 24 minus the value at Baseline

  • Activated memory B cells, transitional B cells [ Time Frame: Assessed At Week 24 ] [ Designated as safety issue: No ]
    Activated memory B cells, transitional B cells will be analysed at Week 24

  • Activated T cells, regulatory T cells, and ratio of activated: regulatory T cells [ Time Frame: Assessed At Week 24 ] [ Designated as safety issue: No ]
    Activated T cells, regulatory T cells, and ratio of activated: regulatory T cells will be analysed at Week 24

  • HLA-specific and donor HLA specific antibody levels [ Time Frame: Assessed Up to Week 52 ] [ Designated as safety issue: No ]
    HLA antibodies assessments will be performed at all time points indicated. Non-HLA exploratory antibodies will be performed at day 0, week 2, 4, 8, 12, 24 and week 52

  • Proportion of subjects with episodes of acute rejection [ Time Frame: Assessed Up to Week 52 ] [ Designated as safety issue: No ]
    Proportion of subjects with the number of episodes, and the long-term impact of episodes will be assessed

  • Serum creatinine assessments [ Time Frame: Assessed Up to 1 year ] [ Designated as safety issue: No ]
  • Estimated glomerular filtration rate (eGFR) [ Time Frame: Assessed up to 1 year ] [ Designated as safety issue: No ]
    Mean Change From Baseline in glomerular filtration rate. GFR (mL/min/1.73 m^2) = 175 * (Scr)^-1.154 * (Age)^-0.203 * (0.742 if female) * (1.212 if African American) (conventional units). (mL, milliliters; min, minute; m^s, meters squared; Scr, serum creatinine)

  • Immunosuppressant/corticosteroid use [ Time Frame: Assessed Up to 1 year ] [ Designated as safety issue: No ]
    Immunosuppressants included basiliximab, mycophenolate mofetil, tacrolimus, prednisolone


Estimated Enrollment: 20
Study Start Date: September 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Belimumab 10 mg
Subjects will receive belimumab 10 mg/ Kilogram (kg) infusion on Days 0, 14, 28 and every 4 weeks thereafter for a total of 7 infusions. The last dose of investigational product will be administered at the Week 20 visit; In addition to investigational product, all subjects will receive standard of care.
Drug: Belimumab
Belimumab (10 mg/kg) will be given as an intravenous solution over a 1 hour time period administered every 4 weeks for 24 weeks (with an additional dose at Week 2)
Placebo Comparator: Placebo
Subjects will receive placebo infusion on Days 0, 14, 28 and every 4 weeks thereafter for a total of 7 infusions. The last dose of investigational product will be administered at the Week 20 visit; In addition to investigational product, all subjects will receive standard of care
Drug: Placebo
Placebo will be given as an intravenous solution over a 1 hour time period administered every 4 weeks for 24 weeks (with an additional dose at Week 2)

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eligible for kidney transplantation: Considered eligible for transplantation after undergoing multidisciplinary evaluation at the institution at which the transplantation will be performed
  • Donor characteristics: Receiving a deceased donor kidney or a living donor kidney allograft
  • Age & Gender: Male or female between 18 and 75 years of age, inclusive, at the time of signing the informed consent
  • Female Subjects: Not pregnant or nursing and at least one of the following conditions apply: a. Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy or postmenopausal defined as 12 months of spontaneous amenorrhea. In the absence of confirmatory laboratory assessments [(a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 million international units per milliliter (MIU/mL) and estradiol < 40 picogram per milliliter (pg/mL) (<147 picomole per liter [pmol/L])] in questionable cases, female subjects will be required to use one of the contraception methods as described by the investigator or designee, until confirmatory results become available; b. Questionable post-menopausal status and agrees to use one of the contraception methods as described by the investigator or designee, from Day 0 until 16 weeks after the last dose of investigational product or until postmenopausal status is confirmed with a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MIU/mL and estradiol status who are using hormone replacement therapy (HRT) will be required to use one of the contraception methods as described by the investigator or designee, until post-menopausal status is confirmed. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method; c. Child-bearing potential and agrees to use one of the contraception methods as described by the investigator or designee, from Day 0 until 16 weeks after the last dose of investigational product.
  • Liver function (most recent values available before transplantation): alanine aminotransferase (ALT) < 2x upper limit of normal (ULN); bilirubin <= 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Immunosuppressants: at the time of transplantation, planned to receive a combination of immunosuppressants including basiliximab, mycophenolate mofetil, tacrolimus, prednisolone

Exclusion Criteria:

  • Donor characteristics: receiving a kidney allograft from a donor with any of the following characteristics: a) cold ischemic time exceeding 36 hours; b) age < 5 years old; c) for donors after brain death (DBD), age >70 years old; d) for donors after cardiac death (DCD) age >70 years old; e) ABO blood type incompatible against the recipient; f) 0 0 0 HLA-A -B -DR mismatch against the recipient by National Health Service Blood and Transplant (NHSBT criteria; g) T- and/or B-cell positive crossmatch by complement dependent cytotoxicity or flow cytometry against the recipient. Note :- (In some situations it may be that a pre-existing T- and/or B-cell positive crossmatch by complement dependent cytotoxicity or flow cytometry against the recipient will only be fully revealed immediately after the transplant; in such situations they will be recorded as having met exclusion criteria and withdraw from further involvement in the study; h) serology positive for hepatitis B (except hepatitis B surface antibody and prior vaccination), hepatitis C or human immunodeficiency virus (HIV)
  • Transplant other than kidney: has previously received a hematopoietic stem cell/marrow transplant or an organ transplant other than a kidney (with the exception of corneal transplantation)
  • Planned immunosuppressant regimen: are being considered for steroid-free or alemtuzumab induction
  • Prior therapy at any time: has ever received any of the following: a) B-cell targeted therapy (e.g., rituximab, other anti-CD20 agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab], BLyS-receptor fusion protein [BR3], TACI fragment, crystallizable (Fc), or belimumab)
  • 364 Day prior therapy: has received any of the following within 364 days before Day 0: a) Cyclophosphamide; b) Abatacept; c) A biologic investigational agent other than B-cell targeted therapy [e.g., abetimus sodium, anti CD40L antibody (e.g., BG9588/ IDEC 131; investigational agent applies to any drug not approved for sale in the country in which it is being used]
  • 90 Day prior therapy: has received any of the following within 90 days before Day 0: a) Anti- Tumor necrosis factor (TNF) or anti-Interleukin (IL)-6 therapy (e.g., adalimumab, etanercept, infliximab, tocilizumab); b) Interleukin-1 receptor antagonists (e.g., anakinra); c) Intravenous immunoglobulin (IVIG); d) Plasmapheresis, leukapheresis
  • 60 Day prior therapy: has received any of the following within 60 days before Day 0: a) A non-biologic investigational agent (investigational agent applies to any drug not approved for sale in the country in which it is being used); b) Any new immunosuppressive/immunomodulatory agent; tacrolimus, Mycophenolate mofetil (MMF), and corticosteroids are permitted. Inhaled steroids and new topical immunosuppressive agents (e.g., eye drops, topical creams) are also allowed.
  • 30 Day prior therapy: has received any of the following within 30 days before Day 0: a) A live vaccine; b) An increase in dose of an immunosuppressive/immunomodulatory agent (decreases in dose or discontinuations are permitted). Increases in doses of tacrolimus, MMF, and corticosteroids are permitted.
  • Malignancy: has a history of malignancy in the past 5 years except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix.
  • Acute or chronic infection: has required management of acute or chronic infections (excludes prophylaxis of infections), as follows: a) Currently receiving any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria), which, in the opinion of the investigator, could put the subject at undue risk; b) Hospitalized for treatment of infection within 30 days before Day 0, which, in the opinion of the investigator, could put the subject at undue risk ; c) Treated for an infection with parenteral (intravenous or intramuscular)] antibiotics (antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within 30 days before Day 0, which, in the opinion of the investigator, could put the subject at undue risk
  • Other disease/conditions: has any of the following: a) clinical evidence of significant unstable or uncontrolled acute or chronic diseases (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, neurological, malignancy or infectious diseases) which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk; b) a surgical procedure planned in the 6 months after Day 0, other than kidney transplantation or related procedure; c) a known history of any other medical disease (e.g., cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the investigator, makes the subject unsuitable for the study
  • Hepatitis: known to have serologic evidence of hepatitis B infection based on the results of testing for hepatitis B surface antigen (HBsAg), or antibodies against hepatitis B core antigen (HBc) and/or hepatitis B surface antigen (HBs) as follows: a) Patients positive for HBsAg are excluded; ) Patients negative for HBsAg and anti-HBc antibody but positive for anti-HBs antibody and with no history of hepatitis B vaccination are excluded; c) Patients negative for HBsAg but positive for both anti-HBc and anti-HBs antibodies are excluded; d) Patients negative for HBsAg and anti-HBs antibody but positive for anti-HBc antibody are excluded; e) Or has known serologic evidence of hepatitis C infection based on the results of testing for hepatitis C antibody and hepatitis C recombinant immunoblot assay (RIBA) as follows: Patients with a positive test for Hepatitis C antibody confirmed on the same sample with a Hepatitis C RIBA immunoblot assay. Patients who are positive for Hepatitis C antibody, and who are negative when the Hepatitis C RIBA immunoblot assay is performed on the same sample, will be eligible to participate. Patients who are positive for Hepatitis C antibody and who have a positive or indeterminate result when the Hepatitis C RIBA immunoblot assay is performed on the same sample, will not be eligible to participate.
  • HIV: known to have a historically positive HIV test or tests positive at screening for HIV.
  • Immunodeficiency: recipient with a history of immunodeficiency (defined as Immunoglobulin A isotype (IgA) level <10 milligrams per deciliter (mg/dL) or have Immunoglobulin G isotype (IgG) level <400 mg/dL).
  • Laboratory abnormalities: has an abnormal laboratory assessment, which is judged clinically significant by the investigator.
  • Lymphopenia: has a lymphocyte count <500/ millimeter (mm)^3.
  • Drug Sensitivity: has a history of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy including a previous anaphylactic reaction to parenteral administration contrast agents, human or murine proteins or monoclonal antibodies that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
  • Substance abuse: has evidence of current drug or alcohol abuse or dependence.
  • Blood donation: where participation in the study would result in donation of blood or blood products in excess of 700 mL within a 56-day period
  • Venous access: has venous access limitations likely to preclude monthly infusions
  • Compliance: is unlikely to comply with scheduled study visits based on investigator judgment or has a history of substance abuse, psychiatric disorder or condition that may compromise communication with the investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01536379

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Locations
United Kingdom
GSK Investigational Site Recruiting
Cambridge, United Kingdom, CB2 0QQ
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Not yet recruiting
London, United Kingdom, SE1 9RT
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01536379     History of Changes
Other Study ID Numbers: 114424
Study First Received: February 16, 2012
Last Updated: September 18, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
Infection
Quality of Life

Additional relevant MeSH terms:
Belimumab
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014