Phase 2
N=25
A Study of Belimumab in the Prevention of Kidney Transplant Rejection
Transplantation, Organ
Bottom Line
View on ClinicalTrials.gov: NCT01536379 ↗Enrolled (actual)
25
Serious AEs
48.0%
Results posted
Apr 2017
Primary outcome: Primary: Change From Baseline in naïve B Cells From Baseline to Week 24 — 4.0; -30.4 cells/mm^3
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Belimumab (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Feb 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in naïve B Cells From Baseline to Week 24 |
4.0; -30.4 | — |
| PRIMARY Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) |
10; 11; 9; 10; 7; 5 | — |
| PRIMARY Number of Incidence of All Infections and Serious Infections |
8; 7; 2; 1; 7; 5 | — |
| PRIMARY Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24 and Week 52 |
-4.444; 7.286; -6.545; 4.200; 2.000; 10.000 | — |
| PRIMARY Change From Baseline in Heart Rate From Baseline at Week 24 and Week 52 |
5.125; 1.500; 2.000; -2.444 | — |
| PRIMARY Change From Baseline in Body Temperature From Baseline at Week 24 and Week 52 |
0.025; -0.233; -0.045; 0.030 | — |
| PRIMARY Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 |
1; 1; 1; 2; 3; 0 | — |
| PRIMARY Number of Participants Outside the Normal Range (NR) for Heart Rate at Week 24 and Week 52 |
1; 0; 2; 0; 0; 0 | — |
| PRIMARY Number of Participants Outside the Normal Range (NR) for Body Temperature at Week 24 and Week 52 |
0; 0; 3; 4; 0; 0 | — |
| PRIMARY Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 |
-0.001; -0.015; 0.033; -0.005; -0.531; -0.140 | — |
| PRIMARY Change From Baseline in the Haematology Parameter- Hemoglobin at Week 24 and Week 52 |
5.4; 13.2; 12.6; 6.3 | — |
| PRIMARY Change From Baseline in the Hematology Parameter- Hematocrit at Week 24 and Week 52 |
0.0216; 0.0477; 0.0434; 0.0238 | — |
| PRIMARY Change From Baseline in Haematology Parameter- Mean Corposcular Hemoglobin (MCH) at Week 24 and Week 52 |
-0.79; -1.37; -1.59; -1.93 | — |
| PRIMARY Change From Baseline in Haematology Parameter- Mean Corposcular Volume (MCV) at Week 24 and Week 52 |
-1.73; -2.55; -3.58; -4.61 | — |
| PRIMARY Change From Baseline in Haematology Parameter- Red Blood Cell (RBC) at Week 24 and Week 52 |
0.298; 0.645; 0.635; 0.468 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameter- Albumin at Week 24 and Week 52 |
4.1; 2.9; 2.9; 1.8 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 |
-16.0; -5.0; -17.5; 19.9; 1.0; 5.1 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 |
0.6; -0.7; 0.9; 0.2; 3.0; 2.7 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 |
0.116; 0.167; 0.116; 0.128; -3.73; 1.70 | — |
| PRIMARY Change From Baseline in Clinical Chemistry Parameter- Glomerular Filtration Rate (GFR) at Week 24 and Week 52 |
42.80; 44.36; 42.33; 53.75 | — |
| PRIMARY Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 |
-0.500; -0.433; -0.300; -0.500; -1.02; -2.40 | — |
| SECONDARY Median Percent Change From Baseline in Memory B Cell Count at Week 24 and Week 52 |
-12.5; 177.8; 2.4; -33.3 | — |
| SECONDARY Activated Memory B Cells Count at Week 24 and Week 52 |
37157.2; 38389.6; 24220.8; 11092.5 | — |
| SECONDARY Activated Memory B Cells Percentage at Week 24 and Week 52 |
32.8; 19.0; 32.0; 38.8 | — |
| SECONDARY Transitional B Cells Count at Week 24 and Week 52 |
5470; 2679; 7110; 6652 | — |
| SECONDARY Transitional B Cells Percentage at Week 24 and Week 52 |
2.43; 1.14; 2.61; 3.41 | — |
| SECONDARY Activated T Cell Count at Week 24 and Week 52 |
109279.5; 78952.7; 122304.7; 75349.4 | — |
| SECONDARY Activated T Cell Percentage at Week 24 and Week 52 |
17.0; 14.0; 15.2; 14.7 | — |
| SECONDARY Regulatory T Cell Count at Week 24 and Week 52 |
23586.2; 24234.5; 33038.7; 27419.8 | — |
| SECONDARY Regulatory T Cell (%CD4) at Week 24 and Week 52 |
4.4; 4.6; 5.0; 4.4 | — |
| SECONDARY Mean Activated: Regulatory T Cell Ratio at Week 24 and Week 52 |
4.88; 3.33; 4.62; 3.61 | — |
| SECONDARY Proportion of Participants With Episodes of Acute Rejection at Week 24 and Week 52 |
0.4; 0.33; 0.6; 0.33 | — |
| SECONDARY Mean Serum Creatinine at Week 24 and Week 52 |
115.1; 112.3; 135.4; 122.6 | — |
| SECONDARY Mean eGFR at Week 24 and Week 52 |
62.25; 49.33; 58.99; 56.29 | — |
| SECONDARY Mean Prednisolone Use at Week 24 |
5.71; 5.27 | — |
Summary
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.
Eligibility 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 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) 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 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 wit
Data sourced from ClinicalTrials.gov (NCT01536379). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.