Transplantation, Organ
Conditions
Keywords
Infection, Quality of Life
Brief 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.
Interventions
DRUGBelimumab
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)
DRUGPlacebo
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)
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Change from Baseline in immunoglobulins IgA, IgG and IgM was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | Week 24 and Week 52 | Number of participants outside the normal range (NR) for SBP and DBP was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Number of participants outside the normal range are summarized by less than (\<) normal range and greater than (\>) normal range categories at Week 24 and Week 52. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Number of Participants Outside the Normal Range (NR) for Heart Rate at Week 24 and Week 52 | Week 24 and Week 52 | Number of participants outside the normal range (NR) for heart rate was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Number of participants outside the normal range are summarized by less than (\<) normal range and greater than (\>) normal range categories at Week 24 and Week 52. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Number of Participants Outside the Normal Range (NR) for Body Temperature at Week 24 and Week 52 | Week 24 and Week 52 | Number of participants outside the normal range (NR) for body temperature was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Number of participants outside the normal range are summarized by less than (\<) normal range and greater than (\>) normal range categories at Week 24 and Week 52. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Hematology parameters included: basophils (B), eosinophils (E), lymphocytes (L), monocytes (M), total neutrophils (N), platelet count (PC) and white blood cells (WBC). Change from Baseline in haematology parameter was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in the Haematology Parameter- Hemoglobin at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Change from Baseline in hemoglobin was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in the Hematology Parameter- Hematocrit at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Haematology Parameter- Mean Corposcular Hemoglobin (MCH) at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Change from Baseline in MCH was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Haematology Parameter- Mean Corposcular Volume (MCV) at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Change from Baseline in MCV was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Haematology Parameter- Red Blood Cell (RBC) at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Change from Baseline in RBC was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Clinical Chemistry Parameter- Albumin at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Change from Baseline in albumin was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Clinical chemistry parameter included alkaline phosphatase (ALP), alanine amino Transferase (ALT) and aspartate amino transferase (AST). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Clinical chemistry parameters included direct bilirubin (DB), total bilirubin (TB) and creatinine (C). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Clinical chemistry parameters included calcium (Ca), carbon dioxide content/bicarbonate (CO2/Bicar), glucose (Gl), potassium (K), sodium (Na), phosphorus inorganic (PhI), urea/blood urine nitrogen (U/BUN). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Clinical Chemistry Parameter- Glomerular Filtration Rate (GFR) at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Change from Baseline in GFR was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Number of Incidence of All Infections and Serious Infections | Up to 1 year | All infections included: 1. Opportunistic infections per-clinical assessment, 2. Herpes Zoster, a. Recurrent, b. Disseminated, 3. Sepsis. Opportunistic infections were identified using list of preferred terms as per Medical Dictionary for Regulatory Activities (MedDRA) version 18.1. Any events falling under these preferred terms were adjudicated to determine if criteria was met for an opportunistic infection. |
| Change From Baseline in naïve B Cells From Baseline to Week 24 | Baseline and Week 24 | Naive B cell is cell that is not exposed to antigen. Naïve B cell count is CD20+CD27 concentration of cells (conc-cell)/cubic millimeter (cumm). Change from Baseline in naïve B cells was calculated as the value at Week 24 minus the value at Baseline. MITT Population consisted of all participants randomized to treatment, who have had taken at least one dose of study. Participants analyzed included those who had data at Week 24 for naïve B cells count (MITT Population). Baseline value used in the analysis was of Day 0 (Day of transplant). Adjusted mean differences (treatment-placebo) and 95% confidence intervals for differences were obtained from mixed-models repeated-measures (MMRM) model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. |
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | Up to 1 year | Number of participants with AEs, SAEs and AESI are summarized. The On-treatment (OT) phase started on the day and time of receiving the start of the first infusion and ended on the last dose date plus 28 days. The Post-treatment (PT) phase started 29 days after day of last dose up to 1 year. An AE is any untoward medical occurrence, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in, death, is life threatening, Requires hospitalization or prolongation of existing hospitalization, Results in disability/incapacity, Is a congenital anomaly/birth defect or event that but may jeopardize the subject or may require medical or surgical intervention to prevent one of the other outcomes listed. AESI included malignant neoplasms, infusion/anaphylaxis/hypersensitivity reactions, all infections, depression/suicide/self-injury, deaths. |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Change from Baseline in SBP and DBP were assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value at Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Heart Rate From Baseline at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Change from Baseline in heart rate was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value at Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Change From Baseline in Body Temperature From Baseline at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Change from Baseline in body temperature was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value at Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Activated Memory B Cells Count at Week 24 and Week 52 | Week 24 and Week 52 | Activated memory B cell-CD95% count is CD19+CD27+CD95 conc-cells/mL. Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Activated Memory B Cells Percentage at Week 24 and Week 52 | Week 24 and Week 52 | Activated memory B cell-CD95% percentage is CD19+CD27+CD95+ (%CD19/CD27). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Transitional B Cells Count at Week 24 and Week 52 | Week 24 and Week 52 | Transitional B cell count (Newell) is CD19+CD24b+CD38b+IgD+ (Conc-cells/mL). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Transitional B Cells Percentage at Week 24 and Week 52 | Week 24 and Week 52 | Transitional B cell percentage (Newell) is CD19+CD24b+CD38b+IgD+ (%CD19+). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Activated T Cell Count at Week 24 and Week 52 | Week 24 and Week 52 | A T cell is a type of lymphocyte that plays a central role in cell-mediated immunity. Activated T cell count Codarri is CD4+ CD25hi CD45RA- IL 7Rhi (Conc-cells/mL). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Activated T Cell Percentage at Week 24 and Week 52 | Week 24 and Week 52 | Activated T cell percentage (Codarri)= CD4+ CD25hi CD45RA- IL 7Rhi (% of CD4+). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Regulatory T Cell Count at Week 24 and Week 52 | Week 24 and Week 52 | Regulatory T cell count is CD4+ CD25hi IL-7Rlo (Conc-cells/mL). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Regulatory T Cell (%CD4) at Week 24 and Week 52 | Week 24 and Week 52 | Regulatory T cell (%CD4) = CD4+ CD25hi IL-7Rlo (% of CD4+). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Mean Activated: Regulatory T Cell Ratio at Week 24 and Week 52 | Week 24 and Week 52 | Activated: regulatory T cell ratio is Activated T cell CD4+CD25hi CD45RA IL 7Rhi (absolute number)/ Regulatory T cell CD4+CD25hi CD45RA IL 7Rlo (absolute number). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Proportion of Participants With Episodes of Acute Rejection at Week 24 and Week 52 | Week 24 and Week 52 | The endpoint diagnosis was made by a proven biopsy result. Number of rejections only counted once per participant. The proportion of participants with episodes of acute rejection was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Mean Serum Creatinine at Week 24 and Week 52 | Week 24 and Week 52 | Adjusted mean difference for serum creatinine values (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction, at Week 24 and Week 52. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). |
| Mean eGFR at Week 24 and Week 52 | Week 24 and Week 52 | The estimated glomerular filtration rate (eGFR) were calculated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation. Adjusted mean difference(treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction at Week 24 and Week 52. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the indicated time points were analyzed (represented by n= X, X in the category titles). |
| Mean Prednisolone Use at Week 24 | Week 24 | Adjusted mean difference (treatment-placebo) for Prednisolone use and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction at Week 24. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments Only those participants available at indicated timepoints were analyzed (represented by n=X, X in the category titles). |
| Median Percent Change From Baseline in Memory B Cell Count at Week 24 and Week 52 | Baseline, Week 24 and Week 52 | Memory B cells are B cell sub-type that are formed within germinal centres following primary infection and are important in generating an accelerated and more robust antibody-mediated immune response in the case of re-infection. Memory B cell count included CD20+CD27+ cells/mm\^3. Baseline value used in the analysis was of Day 0 (Day of transplant). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Percent change from Baseline in Memory B cell count was calculated as the value at Week 24 and Week 52 minus the value at Baseline multiplied by 100. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Median Difference and 95% confidence interval of difference obtained using the Hodges-Lehmann method. |
Countries
United Kingdom
Participant flow
Recruitment details
A total of 30 renal transplant recipients were enrolled, of which 28 were randomized and 25 were transplanted.
Pre-assignment details
Participants were randomized to 1 of the 2 treatments groups in a 1:1 ratio and received standard of care in addition to investigational products (IPs). Participants received IP infusion on Day 0, Day 14, Day 28 and every 4 weeks thereafter for a total of 7 infusions.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. | 13 |
| Belimumab 10mg/kg Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. | 12 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Belimumab 10mg/kg | Total |
|---|---|---|---|
| Age, Continuous | 51.0 Years STANDARD_DEVIATION 14.02 | 54.3 Years STANDARD_DEVIATION 11.02 | 52.6 Years STANDARD_DEVIATION 12.52 |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White/Caucasian | 12 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 9 Participants | 5 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 13 | 9 / 12 |
| serious Total, serious adverse events | 7 / 13 | 5 / 12 |
Outcome results
Primary
Change From Baseline in Body Temperature From Baseline at Week 24 and Week 52
Change from Baseline in body temperature was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value at Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Body Temperature From Baseline at Week 24 and Week 52 | Week 24; n=8, 6 | 0.025 Degree Centigrade | Standard Deviation 0.7025 |
| Placebo | Change From Baseline in Body Temperature From Baseline at Week 24 and Week 52 | Week 52; n=11, 10 | -0.045 Degree Centigrade | Standard Deviation 0.4803 |
| Belimumab 10mg/kg | Change From Baseline in Body Temperature From Baseline at Week 24 and Week 52 | Week 24; n=8, 6 | -0.233 Degree Centigrade | Standard Deviation 0.5007 |
| Belimumab 10mg/kg | Change From Baseline in Body Temperature From Baseline at Week 24 and Week 52 | Week 52; n=11, 10 | 0.030 Degree Centigrade | Standard Deviation 0.5417 |
Primary
Change From Baseline in Clinical Chemistry Parameter- Albumin at Week 24 and Week 52
Change from Baseline in albumin was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Albumin at Week 24 and Week 52 | Week 24; n=9, 7 | 4.1 G/L | Standard Deviation 2.62 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Albumin at Week 24 and Week 52 | Week 52; n=10, 10 | 2.9 G/L | Standard Deviation 3 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Albumin at Week 24 and Week 52 | Week 24; n=9, 7 | 2.9 G/L | Standard Deviation 4.91 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Albumin at Week 24 and Week 52 | Week 52; n=10, 10 | 1.8 G/L | Standard Deviation 4.98 |
Primary
Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52
Clinical chemistry parameter included alkaline phosphatase (ALP), alanine amino Transferase (ALT) and aspartate amino transferase (AST). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 | AST Week 52; n=7, 4 | 3.3 International Unit (IU)/L | Standard Deviation 5.68 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 | ALP Week 24; n=9, 7 | -16.0 International Unit (IU)/L | Standard Deviation 26.14 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 | ALP Week 52; n=10, 10 | -17.5 International Unit (IU)/L | Standard Deviation 35.25 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 | ALT Week 24; n=9, 7 | 1.0 International Unit (IU)/L | Standard Deviation 15.86 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 | ALT Week 52; n=10, 10 | -2.5 International Unit (IU)/L | Standard Deviation 11.16 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 | AST Week 24; n=6, 3 | 3.2 International Unit (IU)/L | Standard Deviation 7.91 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 | ALT Week 52; n=10, 10 | 2.1 International Unit (IU)/L | Standard Deviation 5.8 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 | AST Week 52; n=7, 4 | 9.3 International Unit (IU)/L | Standard Deviation 3.86 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 | ALT Week 24; n=9, 7 | 5.1 International Unit (IU)/L | Standard Deviation 7.56 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 | ALP Week 24; n=9, 7 | -5.0 International Unit (IU)/L | Standard Deviation 60.03 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 | AST Week 24; n=6, 3 | 7.3 International Unit (IU)/L | Standard Deviation 4.04 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 | ALP Week 52; n=10, 10 | 19.9 International Unit (IU)/L | Standard Deviation 80.63 |
Primary
Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52
Clinical chemistry parameters included calcium (Ca), carbon dioxide content/bicarbonate (CO2/Bicar), glucose (Gl), potassium (K), sodium (Na), phosphorus inorganic (PhI), urea/blood urine nitrogen (U/BUN). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | U/BUN Week 52; n=10, 9 | -8.13 Millimole (MMOL)/L | Standard Deviation 14.967 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | K Week 24; n=9, 7 | 0.06 Millimole (MMOL)/L | Standard Deviation 0.723 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | CO2/Bicar Week 24; n=7, 6 | -3.73 Millimole (MMOL)/L | Standard Deviation 5.951 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | K Week 52; n=10, 10 | -0.02 Millimole (MMOL)/L | Standard Deviation 0.535 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | Ca Week 24; n=9, 7 | 0.116 Millimole (MMOL)/L | Standard Deviation 0.1344 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | Na Week 52; n=10, 10 | -0.7 Millimole (MMOL)/L | Standard Deviation 3.71 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | CO2/Bicar Week 52; n=8, 9 | -2.68 Millimole (MMOL)/L | Standard Deviation 5.142 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | PhI Week 24; n=8, 7 | -0.225 Millimole (MMOL)/L | Standard Deviation 0.3843 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | Na Week 24; n=9, 7 | -0.6 Millimole (MMOL)/L | Standard Deviation 4.03 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | PhI Week 52; n=9, 9 | -0.227 Millimole (MMOL)/L | Standard Deviation 0.4234 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | Gl Week 24; n=5, 5 | 0.20 Millimole (MMOL)/L | Standard Deviation 3.093 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | U/BUN Week 24; n=9, 6 | -5.91 Millimole (MMOL)/L | Standard Deviation 12.164 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | Ca Week 52; n=10, 9 | 0.116 Millimole (MMOL)/L | Standard Deviation 0.1013 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | Gl Week 52; n=5, 8 | -0.32 Millimole (MMOL)/L | Standard Deviation 2.483 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | U/BUN Week 52; n=10, 9 | -9.01 Millimole (MMOL)/L | Standard Deviation 7.323 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | Na Week 24; n=9, 7 | 5.9 Millimole (MMOL)/L | Standard Deviation 5.01 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | Ca Week 24; n=9, 7 | 0.167 Millimole (MMOL)/L | Standard Deviation 0.1942 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | Ca Week 52; n=10, 9 | 0.128 Millimole (MMOL)/L | Standard Deviation 0.1386 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | CO2/Bicar Week 24; n=7, 6 | 1.70 Millimole (MMOL)/L | Standard Deviation 3.449 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | CO2/Bicar Week 52; n=8, 9 | 0.77 Millimole (MMOL)/L | Standard Deviation 3.588 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | Gl Week 24; n=5, 5 | -0.04 Millimole (MMOL)/L | Standard Deviation 2.003 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | Gl Week 52; n=5, 8 | 1.79 Millimole (MMOL)/L | Standard Deviation 4.107 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | K Week 24; n=9, 7 | -0.63 Millimole (MMOL)/L | Standard Deviation 0.923 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | K Week 52; n=10, 10 | -0.44 Millimole (MMOL)/L | Standard Deviation 0.877 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | Na Week 52; n=10, 10 | 2.2 Millimole (MMOL)/L | Standard Deviation 4.71 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | PhI Week 24; n=8, 7 | -0.913 Millimole (MMOL)/L | Standard Deviation 0.5862 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | PhI Week 52; n=9, 9 | -0.726 Millimole (MMOL)/L | Standard Deviation 0.5453 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 | U/BUN Week 24; n=9, 6 | -9.47 Millimole (MMOL)/L | Standard Deviation 9.128 |
Primary
Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52
Clinical chemistry parameters included direct bilirubin (DB), total bilirubin (TB) and creatinine (C). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 | DB Week 24; n=8, 3 | 0.6 Micromole per Liter (umol/L) | Standard Deviation 1.51 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 | DB Week 52; n=9, 5 | 0.9 Micromole per Liter (umol/L) | Standard Deviation 1.54 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 | TB Week 24; n=9, 7 | 3.0 Micromole per Liter (umol/L) | Standard Deviation 6.5 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 | TB Week 52; n=10, 10 | 2.9 Micromole per Liter (umol/L) | Standard Deviation 5.26 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 | C Week 24; n=9, 7 | -471.1 Micromole per Liter (umol/L) | Standard Deviation 317.54 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 | C Week 52; n=10, 10 | -468.4 Micromole per Liter (umol/L) | Standard Deviation 310.54 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 | C Week 24; n=9, 7 | -571.3 Micromole per Liter (umol/L) | Standard Deviation 183.53 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 | DB Week 24; n=8, 3 | -0.7 Micromole per Liter (umol/L) | Standard Deviation 3.06 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 | TB Week 52; n=10, 10 | 2.9 Micromole per Liter (umol/L) | Standard Deviation 3.38 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 | DB Week 52; n=9, 5 | 0.2 Micromole per Liter (umol/L) | Standard Deviation 1.3 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 | C Week 52; n=10, 10 | -609.8 Micromole per Liter (umol/L) | Standard Deviation 271.89 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 | TB Week 24; n=9, 7 | 2.7 Micromole per Liter (umol/L) | Standard Deviation 5.22 |
Primary
Change From Baseline in Clinical Chemistry Parameter- Glomerular Filtration Rate (GFR) at Week 24 and Week 52
Change from Baseline in GFR was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Glomerular Filtration Rate (GFR) at Week 24 and Week 52 | Week 52; n=10, 10 | 42.33 milliliter (mL)/Minute (min) | Standard Deviation 29.14 |
| Placebo | Change From Baseline in Clinical Chemistry Parameter- Glomerular Filtration Rate (GFR) at Week 24 and Week 52 | Week 24; n=9, 7 | 42.80 milliliter (mL)/Minute (min) | Standard Deviation 23.604 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Glomerular Filtration Rate (GFR) at Week 24 and Week 52 | Week 52; n=10, 10 | 53.75 milliliter (mL)/Minute (min) | Standard Deviation 15.176 |
| Belimumab 10mg/kg | Change From Baseline in Clinical Chemistry Parameter- Glomerular Filtration Rate (GFR) at Week 24 and Week 52 | Week 24; n=9, 7 | 44.36 milliliter (mL)/Minute (min) | Standard Deviation 10.731 |
Primary
Change From Baseline in Haematology Parameter- Mean Corposcular Hemoglobin (MCH) at Week 24 and Week 52
Change from Baseline in MCH was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Haematology Parameter- Mean Corposcular Hemoglobin (MCH) at Week 24 and Week 52 | Week 24; n=8, 6 | -0.79 Picogram (pg) | Standard Deviation 2.173 |
| Placebo | Change From Baseline in Haematology Parameter- Mean Corposcular Hemoglobin (MCH) at Week 24 and Week 52 | Week 52; n=10, 10 | -1.59 Picogram (pg) | Standard Deviation 1.516 |
| Belimumab 10mg/kg | Change From Baseline in Haematology Parameter- Mean Corposcular Hemoglobin (MCH) at Week 24 and Week 52 | Week 24; n=8, 6 | -1.37 Picogram (pg) | Standard Deviation 2.683 |
| Belimumab 10mg/kg | Change From Baseline in Haematology Parameter- Mean Corposcular Hemoglobin (MCH) at Week 24 and Week 52 | Week 52; n=10, 10 | -1.93 Picogram (pg) | Standard Deviation 2.743 |
Primary
Change From Baseline in Haematology Parameter- Mean Corposcular Volume (MCV) at Week 24 and Week 52
Change from Baseline in MCV was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Haematology Parameter- Mean Corposcular Volume (MCV) at Week 24 and Week 52 | Week 24; n=9, 6 | -1.73 Femtoliter (FL) | Standard Deviation 6.43 |
| Placebo | Change From Baseline in Haematology Parameter- Mean Corposcular Volume (MCV) at Week 24 and Week 52 | Week 52; n=11, 10 | -3.58 Femtoliter (FL) | Standard Deviation 4.34 |
| Belimumab 10mg/kg | Change From Baseline in Haematology Parameter- Mean Corposcular Volume (MCV) at Week 24 and Week 52 | Week 24; n=9, 6 | -2.55 Femtoliter (FL) | Standard Deviation 8.198 |
| Belimumab 10mg/kg | Change From Baseline in Haematology Parameter- Mean Corposcular Volume (MCV) at Week 24 and Week 52 | Week 52; n=11, 10 | -4.61 Femtoliter (FL) | Standard Deviation 7.041 |
Primary
Change From Baseline in Haematology Parameter- Red Blood Cell (RBC) at Week 24 and Week 52
Change from Baseline in RBC was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Haematology Parameter- Red Blood Cell (RBC) at Week 24 and Week 52 | Week 24; n=9, 6 | 0.298 Tera (TI)/L | Standard Deviation 0.6716 |
| Placebo | Change From Baseline in Haematology Parameter- Red Blood Cell (RBC) at Week 24 and Week 52 | Week 52; n=11, 10 | 0.635 Tera (TI)/L | Standard Deviation 0.7064 |
| Belimumab 10mg/kg | Change From Baseline in Haematology Parameter- Red Blood Cell (RBC) at Week 24 and Week 52 | Week 52; n=11, 10 | 0.468 Tera (TI)/L | Standard Deviation 0.5884 |
| Belimumab 10mg/kg | Change From Baseline in Haematology Parameter- Red Blood Cell (RBC) at Week 24 and Week 52 | Week 24; n=9, 6 | 0.645 Tera (TI)/L | Standard Deviation 0.8097 |
Primary
Change From Baseline in Heart Rate From Baseline at Week 24 and Week 52
Change from Baseline in heart rate was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value at Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Heart Rate From Baseline at Week 24 and Week 52 | Week 24; n=8, 6 | 5.125 Beats per minute (BPM) | Standard Deviation 16.8983 |
| Placebo | Change From Baseline in Heart Rate From Baseline at Week 24 and Week 52 | Week 52; n=11, 9 | 2.000 Beats per minute (BPM) | Standard Deviation 11.5065 |
| Belimumab 10mg/kg | Change From Baseline in Heart Rate From Baseline at Week 24 and Week 52 | Week 52; n=11, 9 | -2.444 Beats per minute (BPM) | Standard Deviation 15.42 |
| Belimumab 10mg/kg | Change From Baseline in Heart Rate From Baseline at Week 24 and Week 52 | Week 24; n=8, 6 | 1.500 Beats per minute (BPM) | Standard Deviation 13.6345 |
Primary
Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52
Change from Baseline in immunoglobulins IgA, IgG and IgM was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 | IgA Week 24; n=2, 3 | -0.500 G/L | Standard Deviation 0.2828 |
| Placebo | Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 | IgA Week 52; n=2, 3 | -0.300 G/L | Standard Deviation 0 |
| Placebo | Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 | IgG Week 24; n=6, 6 | -1.02 G/L | Standard Deviation 1.184 |
| Placebo | Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 | IgG Week 52; n=10, 9 | 0.78 G/L | Standard Deviation 3.595 |
| Placebo | Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 | IgM Week 24; n=2, 3 | -0.100 G/L | Standard Deviation 0 |
| Placebo | Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 | IgM Week 52; n=2, 3 | 0.0000 G/L | Standard Deviation 0 |
| Belimumab 10mg/kg | Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 | IgM Week 24; n=2, 3 | -0.133 G/L | Standard Deviation 0.3512 |
| Belimumab 10mg/kg | Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 | IgA Week 24; n=2, 3 | -0.433 G/L | Standard Deviation 0.6429 |
| Belimumab 10mg/kg | Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 | IgG Week 52; n=10, 9 | -2.13 G/L | Standard Deviation 1.702 |
| Belimumab 10mg/kg | Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 | IgA Week 52; n=2, 3 | -0.500 G/L | Standard Deviation 0.5292 |
| Belimumab 10mg/kg | Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 | IgM Week 52; n=2, 3 | -0.333 G/L | Standard Deviation 0.4933 |
| Belimumab 10mg/kg | Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 | IgG Week 24; n=6, 6 | -2.40 G/L | Standard Deviation 1.731 |
Primary
Change From Baseline in naïve B Cells From Baseline to Week 24
Naive B cell is cell that is not exposed to antigen. Naïve B cell count is CD20+CD27 concentration of cells (conc-cell)/cubic millimeter (cumm). Change from Baseline in naïve B cells was calculated as the value at Week 24 minus the value at Baseline. MITT Population consisted of all participants randomized to treatment, who have had taken at least one dose of study. Participants analyzed included those who had data at Week 24 for naïve B cells count (MITT Population). Baseline value used in the analysis was of Day 0 (Day of transplant). Adjusted mean differences (treatment-placebo) and 95% confidence intervals for differences were obtained from mixed-models repeated-measures (MMRM) model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments.
Time frame: Baseline and Week 24
Population: Modified Intent to treat (MITT) Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in naïve B Cells From Baseline to Week 24 | 4.0 cells/mm^3 | Standard Error 25.55 |
| Belimumab 10mg/kg | Change From Baseline in naïve B Cells From Baseline to Week 24 | -30.4 cells/mm^3 | Standard Error 27.5 |
95% CI: [-109.5, 40.7]
Primary
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24 and Week 52
Change from Baseline in SBP and DBP were assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value at Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24 and Week 52 | DBP Week 52; n=11, 10 | -6.545 millimeter of mercury (mmHg) | Standard Deviation 13.9668 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24 and Week 52 | SBP Week 52; n=11, 10 | -2.909 millimeter of mercury (mmHg) | Standard Deviation 27.2046 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24 and Week 52 | SBP Week 24; n=9, 7 | 2.000 millimeter of mercury (mmHg) | Standard Deviation 26.096 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24 and Week 52 | DBP Week 24; n=9, 7 | -4.444 millimeter of mercury (mmHg) | Standard Deviation 14.3275 |
| Belimumab 10mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24 and Week 52 | DBP Week 52; n=11, 10 | 4.200 millimeter of mercury (mmHg) | Standard Deviation 8.5479 |
| Belimumab 10mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24 and Week 52 | DBP Week 24; n=9, 7 | 7.286 millimeter of mercury (mmHg) | Standard Deviation 13.8289 |
| Belimumab 10mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24 and Week 52 | SBP Week 24; n=9, 7 | 10.000 millimeter of mercury (mmHg) | Standard Deviation 35.9444 |
| Belimumab 10mg/kg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24 and Week 52 | SBP Week 52; n=11, 10 | 3.300 millimeter of mercury (mmHg) | Standard Deviation 27.9008 |
Primary
Change From Baseline in the Haematology Parameter- Hemoglobin at Week 24 and Week 52
Change from Baseline in hemoglobin was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Haematology Parameter- Hemoglobin at Week 24 and Week 52 | Week 24; n=9, 6 | 5.4 Grams per Liter (G/L) | Standard Deviation 24.84 |
| Placebo | Change From Baseline in the Haematology Parameter- Hemoglobin at Week 24 and Week 52 | Week 52; n=11, 10 | 12.6 Grams per Liter (G/L) | Standard Deviation 22.69 |
| Belimumab 10mg/kg | Change From Baseline in the Haematology Parameter- Hemoglobin at Week 24 and Week 52 | Week 24; n=9, 6 | 13.2 Grams per Liter (G/L) | Standard Deviation 28.9 |
| Belimumab 10mg/kg | Change From Baseline in the Haematology Parameter- Hemoglobin at Week 24 and Week 52 | Week 52; n=11, 10 | 6.3 Grams per Liter (G/L) | Standard Deviation 23.48 |
Primary
Change From Baseline in the Hematology Parameter- Hematocrit at Week 24 and Week 52
Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Hematology Parameter- Hematocrit at Week 24 and Week 52 | Week 24; n=9, 6 | 0.0216 Percentage of blood | Standard Deviation 0.06625 |
| Placebo | Change From Baseline in the Hematology Parameter- Hematocrit at Week 24 and Week 52 | Week 52; n=11, 10 | 0.0434 Percentage of blood | Standard Deviation 0.06813 |
| Belimumab 10mg/kg | Change From Baseline in the Hematology Parameter- Hematocrit at Week 24 and Week 52 | Week 24; n=9, 6 | 0.0477 Percentage of blood | Standard Deviation 0.0954 |
| Belimumab 10mg/kg | Change From Baseline in the Hematology Parameter- Hematocrit at Week 24 and Week 52 | Week 52; n=11, 10 | 0.0238 Percentage of blood | Standard Deviation 0.07045 |
Primary
Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52
Hematology parameters included: basophils (B), eosinophils (E), lymphocytes (L), monocytes (M), total neutrophils (N), platelet count (PC) and white blood cells (WBC). Change from Baseline in haematology parameter was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | L Week 52; n=10, 10 | 0.085 Gills/Liter (GI/L) | Standard Deviation 0.5841 |
| Placebo | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | M Week 24; n=9, 6 | -0.097 Gills/Liter (GI/L) | Standard Deviation 0.2231 |
| Placebo | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | B Week 24; n=9, 6 | -0.001 Gills/Liter (GI/L) | Standard Deviation 0.0215 |
| Placebo | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | M Week 52; n=10, 10 | 0.001 Gills/Liter (GI/L) | Standard Deviation 0.1799 |
| Placebo | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | B Week 52; n=10, 10 | 0.033 Gills/Liter (GI/L) | Standard Deviation 0.1024 |
| Placebo | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | TN Week 24; n=9, 6 | 0.946 Gills/Liter (GI/L) | Standard Deviation 2.6602 |
| Placebo | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | PC Week 24; n=9, 6 | 15.9 Gills/Liter (GI/L) | Standard Deviation 59.64 |
| Placebo | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | TN Week 52; n=10, 10 | 1.657 Gills/Liter (GI/L) | Standard Deviation 3.5533 |
| Placebo | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | E Week 24; n=9, 6 | -0.531 Gills/Liter (GI/L) | Standard Deviation 1.025 |
| Placebo | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | WBC Week 52; n=11, 10 | 1.47 Gills/Liter (GI/L) | Standard Deviation 3.572 |
| Placebo | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | PC Week 52; n=11, 10 | 18.1 Gills/Liter (GI/L) | Standard Deviation 55.81 |
| Placebo | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | E Week 52; n=10, 10 | -0.392 Gills/Liter (GI/L) | Standard Deviation 0.8048 |
| Placebo | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | WBC Week 24; n=9, 6 | 0.10 Gills/Liter (GI/L) | Standard Deviation 3.483 |
| Placebo | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | L Week 24; n=9, 6 | -0.218 Gills/Liter (GI/L) | Standard Deviation 0.6457 |
| Belimumab 10mg/kg | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | WBC Week 24; n=9, 6 | -0.95 Gills/Liter (GI/L) | Standard Deviation 2.868 |
| Belimumab 10mg/kg | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | L Week 24; n=9, 6 | -0.347 Gills/Liter (GI/L) | Standard Deviation 0.3467 |
| Belimumab 10mg/kg | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | L Week 52; n=10, 10 | -0.245 Gills/Liter (GI/L) | Standard Deviation 0.3357 |
| Belimumab 10mg/kg | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | WBC Week 52; n=11, 10 | -1.11 Gills/Liter (GI/L) | Standard Deviation 3.557 |
| Belimumab 10mg/kg | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | B Week 52; n=10, 10 | -0.005 Gills/Liter (GI/L) | Standard Deviation 0.0357 |
| Belimumab 10mg/kg | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | E Week 24; n=9, 6 | -0.140 Gills/Liter (GI/L) | Standard Deviation 0.1274 |
| Belimumab 10mg/kg | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | E Week 52; n=10, 10 | -0.127 Gills/Liter (GI/L) | Standard Deviation 0.1489 |
| Belimumab 10mg/kg | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | M Week 24; n=9, 6 | -0.365 Gills/Liter (GI/L) | Standard Deviation 0.3509 |
| Belimumab 10mg/kg | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | M Week 52; n=10, 10 | -0.111 Gills/Liter (GI/L) | Standard Deviation 0.3892 |
| Belimumab 10mg/kg | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | TN Week 24; n=9, 6 | -0.083 Gills/Liter (GI/L) | Standard Deviation 2.4752 |
| Belimumab 10mg/kg | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | TN Week 52; n=10, 10 | -0.606 Gills/Liter (GI/L) | Standard Deviation 3.3406 |
| Belimumab 10mg/kg | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | PC Week 24; n=9, 6 | 7.3 Gills/Liter (GI/L) | Standard Deviation 40.35 |
| Belimumab 10mg/kg | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | PC Week 52; n=11, 10 | -10.0 Gills/Liter (GI/L) | Standard Deviation 54.14 |
| Belimumab 10mg/kg | Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 | B Week 24; n=9, 6 | -0.015 Gills/Liter (GI/L) | Standard Deviation 0.0207 |
Primary
Number of Incidence of All Infections and Serious Infections
All infections included: 1. Opportunistic infections per-clinical assessment, 2. Herpes Zoster, a. Recurrent, b. Disseminated, 3. Sepsis. Opportunistic infections were identified using list of preferred terms as per Medical Dictionary for Regulatory Activities (MedDRA) version 18.1. Any events falling under these preferred terms were adjudicated to determine if criteria was met for an opportunistic infection.
Time frame: Up to 1 year
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Incidence of All Infections and Serious Infections | All Infections | 8 Infections |
| Placebo | Number of Incidence of All Infections and Serious Infections | Serious Infections | 2 Infections |
| Placebo | Number of Incidence of All Infections and Serious Infections | All Opportunistic Infections | 7 Infections |
| Placebo | Number of Incidence of All Infections and Serious Infections | Serious Opportunistic Infections | 1 Infections |
| Placebo | Number of Incidence of All Infections and Serious Infections | All Herpes Zoster | 0 Infections |
| Placebo | Number of Incidence of All Infections and Serious Infections | Serious Herpes Zoster | 0 Infections |
| Placebo | Number of Incidence of All Infections and Serious Infections | Sepsis | 3 Infections |
| Placebo | Number of Incidence of All Infections and Serious Infections | Serious Sepsis | 2 Infections |
| Belimumab 10mg/kg | Number of Incidence of All Infections and Serious Infections | Serious Sepsis | 1 Infections |
| Belimumab 10mg/kg | Number of Incidence of All Infections and Serious Infections | All Infections | 7 Infections |
| Belimumab 10mg/kg | Number of Incidence of All Infections and Serious Infections | All Herpes Zoster | 1 Infections |
| Belimumab 10mg/kg | Number of Incidence of All Infections and Serious Infections | Serious Infections | 1 Infections |
| Belimumab 10mg/kg | Number of Incidence of All Infections and Serious Infections | Sepsis | 2 Infections |
| Belimumab 10mg/kg | Number of Incidence of All Infections and Serious Infections | All Opportunistic Infections | 5 Infections |
| Belimumab 10mg/kg | Number of Incidence of All Infections and Serious Infections | Serious Herpes Zoster | 0 Infections |
| Belimumab 10mg/kg | Number of Incidence of All Infections and Serious Infections | Serious Opportunistic Infections | 0 Infections |
Primary
Number of Participants Outside the Normal Range (NR) for Body Temperature at Week 24 and Week 52
Number of participants outside the normal range (NR) for body temperature was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Number of participants outside the normal range are summarized by less than (\<) normal range and greater than (\>) normal range categories at Week 24 and Week 52. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Outside the Normal Range (NR) for Body Temperature at Week 24 and Week 52 | < NR Week 24; n=8, 6 | 3 Participants |
| Placebo | Number of Participants Outside the Normal Range (NR) for Body Temperature at Week 24 and Week 52 | > NR Week 52; n=11, 10 | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range (NR) for Body Temperature at Week 24 and Week 52 | < NR Week 52; n=11, 10 | 5 Participants |
| Placebo | Number of Participants Outside the Normal Range (NR) for Body Temperature at Week 24 and Week 52 | > NR Week 24; n=8, 6 | 0 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for Body Temperature at Week 24 and Week 52 | < NR Week 52; n=11, 10 | 2 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for Body Temperature at Week 24 and Week 52 | > NR Week 52; n=11, 10 | 0 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for Body Temperature at Week 24 and Week 52 | < NR Week 24; n=8, 6 | 4 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for Body Temperature at Week 24 and Week 52 | > NR Week 24; n=8, 6 | 0 Participants |
Primary
Number of Participants Outside the Normal Range (NR) for Heart Rate at Week 24 and Week 52
Number of participants outside the normal range (NR) for heart rate was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Number of participants outside the normal range are summarized by less than (\<) normal range and greater than (\>) normal range categories at Week 24 and Week 52. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Outside the Normal Range (NR) for Heart Rate at Week 24 and Week 52 | > NR Week 24; n=8, 6 | 1 Participants |
| Placebo | Number of Participants Outside the Normal Range (NR) for Heart Rate at Week 24 and Week 52 | > NR Week 52; n=11, 9 | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range (NR) for Heart Rate at Week 24 and Week 52 | < NR Week 52; n=11, 9 | 1 Participants |
| Placebo | Number of Participants Outside the Normal Range (NR) for Heart Rate at Week 24 and Week 52 | < NR Week 24; n=8, 6 | 2 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for Heart Rate at Week 24 and Week 52 | < NR Week 24; n=8, 6 | 0 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for Heart Rate at Week 24 and Week 52 | > NR Week 24; n=8, 6 | 0 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for Heart Rate at Week 24 and Week 52 | < NR Week 52; n=11, 9 | 1 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for Heart Rate at Week 24 and Week 52 | > NR Week 52; n=11, 9 | 0 Participants |
Primary
Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52
Number of participants outside the normal range (NR) for SBP and DBP was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Number of participants outside the normal range are summarized by less than (\<) normal range and greater than (\>) normal range categories at Week 24 and Week 52. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | DBP, > NR, Week 52; n=11, 10 | 3 Participants |
| Placebo | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | SBP, < NR, Week 52; n=11, 10 | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | SBP, > NR, Week 24; n=9, 7 | 5 Participants |
| Placebo | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | DBP, > NR, Week 24; n=9, 7 | 1 Participants |
| Placebo | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | SBP, > NR, Week 52; n=11, 10 | 5 Participants |
| Placebo | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | DBP, < NR, Week 24; n=9, 7 | 1 Participants |
| Placebo | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | DBP, < NR, Week 52; n=11, 10 | 2 Participants |
| Placebo | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | SBP, < NR, Week 24; n=9, 7 | 0 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | SBP, > NR, Week 52; n=11, 10 | 4 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | DBP, > NR, Week 52; n=11, 10 | 0 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | DBP, < NR, Week 52; n=11, 10 | 1 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | SBP, > NR, Week 24; n=9, 7 | 3 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | SBP, < NR, Week 24; n=9, 7 | 0 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | DBP, < NR, Week 24; n=9, 7 | 2 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | SBP, < NR, Week 52; n=11, 10 | 1 Participants |
| Belimumab 10mg/kg | Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 | DBP, > NR, Week 24; n=9, 7 | 1 Participants |
Primary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)
Number of participants with AEs, SAEs and AESI are summarized. The On-treatment (OT) phase started on the day and time of receiving the start of the first infusion and ended on the last dose date plus 28 days. The Post-treatment (PT) phase started 29 days after day of last dose up to 1 year. An AE is any untoward medical occurrence, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in, death, is life threatening, Requires hospitalization or prolongation of existing hospitalization, Results in disability/incapacity, Is a congenital anomaly/birth defect or event that but may jeopardize the subject or may require medical or surgical intervention to prevent one of the other outcomes listed. AESI included malignant neoplasms, infusion/anaphylaxis/hypersensitivity reactions, all infections, depression/suicide/self-injury, deaths.
Time frame: Up to 1 year
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | PT AEs | 9 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | Post-Infusion Systemic Reactions | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | PT SAEs | 2 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | All Infections | 6 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | Depression/suicide/self-injury | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | OT SAEs | 7 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | Deaths | 1 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | Malignant neoplasms | 0 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | OT AEs | 10 Participants |
| Belimumab 10mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | All Infections | 7 Participants |
| Belimumab 10mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | OT AEs | 11 Participants |
| Belimumab 10mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | PT AEs | 10 Participants |
| Belimumab 10mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | OT SAEs | 5 Participants |
| Belimumab 10mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | PT SAEs | 2 Participants |
| Belimumab 10mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | Malignant neoplasms | 0 Participants |
| Belimumab 10mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | Post-Infusion Systemic Reactions | 1 Participants |
| Belimumab 10mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | Depression/suicide/self-injury | 0 Participants |
| Belimumab 10mg/kg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) | Deaths | 0 Participants |
Secondary
Activated Memory B Cells Count at Week 24 and Week 52
Activated memory B cell-CD95% count is CD19+CD27+CD95 conc-cells/mL. Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Activated Memory B Cells Count at Week 24 and Week 52 | Week 24; n=9, 7 | 37157.2 cells/mL | Standard Error 16664.42 |
| Placebo | Activated Memory B Cells Count at Week 24 and Week 52 | Week 52; n=10, 8 | 24220.8 cells/mL | Standard Error 15744.17 |
| Belimumab 10mg/kg | Activated Memory B Cells Count at Week 24 and Week 52 | Week 24; n=9, 7 | 38389.6 cells/mL | Standard Error 18682.83 |
| Belimumab 10mg/kg | Activated Memory B Cells Count at Week 24 and Week 52 | Week 52; n=10, 8 | 11092.5 cells/mL | Standard Error 17711.36 |
95% CI: [-50457, 52921.8]
95% CI: [-61868.9, 35612.2]
Secondary
Activated Memory B Cells Percentage at Week 24 and Week 52
Activated memory B cell-CD95% percentage is CD19+CD27+CD95+ (%CD19/CD27). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Activated Memory B Cells Percentage at Week 24 and Week 52 | Week 24; n=9, 7 | 32.8 Percentage of activated memory B cells | Standard Error 5.94 |
| Placebo | Activated Memory B Cells Percentage at Week 24 and Week 52 | Week 52; n=11, 10 | 32.0 Percentage of activated memory B cells | Standard Error 5.07 |
| Belimumab 10mg/kg | Activated Memory B Cells Percentage at Week 24 and Week 52 | Week 24; n=9, 7 | 19.0 Percentage of activated memory B cells | Standard Error 6.06 |
| Belimumab 10mg/kg | Activated Memory B Cells Percentage at Week 24 and Week 52 | Week 52; n=11, 10 | 38.8 Percentage of activated memory B cells | Standard Error 5.48 |
95% CI: [-31.3, 3.7]
95% CI: [-8.6, 22.2]
Secondary
Activated T Cell Count at Week 24 and Week 52
A T cell is a type of lymphocyte that plays a central role in cell-mediated immunity. Activated T cell count Codarri is CD4+ CD25hi CD45RA- IL 7Rhi (Conc-cells/mL). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Activated T Cell Count at Week 24 and Week 52 | Week 24; n=9, 6 | 109279.5 cells/mL | Standard Error 22998.02 |
| Placebo | Activated T Cell Count at Week 24 and Week 52 | Week 52; n=10, 7 | 122304.7 cells/mL | Standard Error 21898.24 |
| Belimumab 10mg/kg | Activated T Cell Count at Week 24 and Week 52 | Week 24; n=9, 6 | 78952.7 cells/mL | Standard Error 26155.19 |
| Belimumab 10mg/kg | Activated T Cell Count at Week 24 and Week 52 | Week 52; n=10, 7 | 75349.4 cells/mL | Standard Error 24313.62 |
95% CI: [-100559.1, 39905.3]
95% CI: [-113218.9, 19308.3]
Secondary
Activated T Cell Percentage at Week 24 and Week 52
Activated T cell percentage (Codarri)= CD4+ CD25hi CD45RA- IL 7Rhi (% of CD4+). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Activated T Cell Percentage at Week 24 and Week 52 | Week 24; n=9, 6 | 17.0 Percentage of activated T cell | Standard Error 2.29 |
| Placebo | Activated T Cell Percentage at Week 24 and Week 52 | Week 52; n=10, 7 | 15.2 Percentage of activated T cell | Standard Error 2.15 |
| Belimumab 10mg/kg | Activated T Cell Percentage at Week 24 and Week 52 | Week 24; n=9, 6 | 14.0 Percentage of activated T cell | Standard Error 2.58 |
| Belimumab 10mg/kg | Activated T Cell Percentage at Week 24 and Week 52 | Week 52; n=10, 7 | 14.7 Percentage of activated T cell | Standard Error 2.33 |
95% CI: [-10.1, 4.2]
95% CI: [-7.2, 6.3]
Secondary
Mean Activated: Regulatory T Cell Ratio at Week 24 and Week 52
Activated: regulatory T cell ratio is Activated T cell CD4+CD25hi CD45RA IL 7Rhi (absolute number)/ Regulatory T cell CD4+CD25hi CD45RA IL 7Rlo (absolute number). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Activated: Regulatory T Cell Ratio at Week 24 and Week 52 | Week 24; n= 9, 6 | 4.88 Ratio | Standard Error 0.832 |
| Placebo | Mean Activated: Regulatory T Cell Ratio at Week 24 and Week 52 | Week 52; n= 10, 7 | 4.62 Ratio | Standard Error 0.779 |
| Belimumab 10mg/kg | Mean Activated: Regulatory T Cell Ratio at Week 24 and Week 52 | Week 24; n= 9, 6 | 3.33 Ratio | Standard Error 0.915 |
| Belimumab 10mg/kg | Mean Activated: Regulatory T Cell Ratio at Week 24 and Week 52 | Week 52; n= 10, 7 | 3.61 Ratio | Standard Error 0.942 |
95% CI: [-4.07, 0.98]
95% CI: [-3.68, 1.67]
Secondary
Mean eGFR at Week 24 and Week 52
The estimated glomerular filtration rate (eGFR) were calculated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation. Adjusted mean difference(treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction at Week 24 and Week 52. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the indicated time points were analyzed (represented by n= X, X in the category titles).
Time frame: Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean eGFR at Week 24 and Week 52 | Week 52; n= 10, 10 | 58.99 mL/minute/1.73 square meter (m^2) | Standard Error 5.732 |
| Placebo | Mean eGFR at Week 24 and Week 52 | Week 24; n=9, 7 | 62.25 mL/minute/1.73 square meter (m^2) | Standard Error 6.119 |
| Belimumab 10mg/kg | Mean eGFR at Week 24 and Week 52 | Week 24; n=9, 7 | 49.33 mL/minute/1.73 square meter (m^2) | Standard Error 6.897 |
| Belimumab 10mg/kg | Mean eGFR at Week 24 and Week 52 | Week 52; n= 10, 10 | 56.29 mL/minute/1.73 square meter (m^2) | Standard Error 5.765 |
95% CI: [-31.56, 5.71]
95% CI: [-19.11, 13.72]
Secondary
Mean Prednisolone Use at Week 24
Adjusted mean difference (treatment-placebo) for Prednisolone use and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction at Week 24. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments Only those participants available at indicated timepoints were analyzed (represented by n=X, X in the category titles).
Time frame: Week 24
Population: mITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Prednisolone Use at Week 24 | 5.71 mg/day | Standard Error 1.438 |
| Belimumab 10mg/kg | Mean Prednisolone Use at Week 24 | 5.27 mg/day | Standard Error 1.713 |
95% CI: [-4.84, 3.96]
Secondary
Mean Serum Creatinine at Week 24 and Week 52
Adjusted mean difference for serum creatinine values (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction, at Week 24 and Week 52. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Serum Creatinine at Week 24 and Week 52 | Week 24; n=9, 7 | 115.1 micromole/L | Standard Error 35.24 |
| Placebo | Mean Serum Creatinine at Week 24 and Week 52 | Week 52; n= 10, 10 | 135.4 micromole/L | Standard Error 33.5 |
| Belimumab 10mg/kg | Mean Serum Creatinine at Week 24 and Week 52 | Week 24; n=9, 7 | 112.3 micromole/L | Standard Error 38.2 |
| Belimumab 10mg/kg | Mean Serum Creatinine at Week 24 and Week 52 | Week 52; n= 10, 10 | 122.6 micromole/L | Standard Error 33.37 |
95% CI: [-105.9, 100.3]
95% CI: [-107.1, 81.4]
Secondary
Median Percent Change From Baseline in Memory B Cell Count at Week 24 and Week 52
Memory B cells are B cell sub-type that are formed within germinal centres following primary infection and are important in generating an accelerated and more robust antibody-mediated immune response in the case of re-infection. Memory B cell count included CD20+CD27+ cells/mm\^3. Baseline value used in the analysis was of Day 0 (Day of transplant). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Percent change from Baseline in Memory B cell count was calculated as the value at Week 24 and Week 52 minus the value at Baseline multiplied by 100. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Median Difference and 95% confidence interval of difference obtained using the Hodges-Lehmann method.
Time frame: Baseline, Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Median Percent Change From Baseline in Memory B Cell Count at Week 24 and Week 52 | Week 24; n=9, 7 | -12.5 Percent change |
| Placebo | Median Percent Change From Baseline in Memory B Cell Count at Week 24 and Week 52 | Week 52; n=10, 7 | 2.4 Percent change |
| Belimumab 10mg/kg | Median Percent Change From Baseline in Memory B Cell Count at Week 24 and Week 52 | Week 24; n=9, 7 | 177.8 Percent change |
| Belimumab 10mg/kg | Median Percent Change From Baseline in Memory B Cell Count at Week 24 and Week 52 | Week 52; n=10, 7 | -33.3 Percent change |
95% CI: [90, 550]
95% CI: [-169.84, 25]
Secondary
Proportion of Participants With Episodes of Acute Rejection at Week 24 and Week 52
The endpoint diagnosis was made by a proven biopsy result. Number of rejections only counted once per participant. The proportion of participants with episodes of acute rejection was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Week 24 and Week 52
Population: mITT Population. Participants analyzed had at least one biopsy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Proportion of Participants With Episodes of Acute Rejection at Week 24 and Week 52 | Week 24; n=5, 6 | 0.4 Proportion of participants |
| Placebo | Proportion of Participants With Episodes of Acute Rejection at Week 24 and Week 52 | Week 52; n=5, 6 | 0.6 Proportion of participants |
| Belimumab 10mg/kg | Proportion of Participants With Episodes of Acute Rejection at Week 24 and Week 52 | Week 24; n=5, 6 | 0.33 Proportion of participants |
| Belimumab 10mg/kg | Proportion of Participants With Episodes of Acute Rejection at Week 24 and Week 52 | Week 52; n=5, 6 | 0.33 Proportion of participants |
95% CI: [-0.638, 0.505]
95% CI: [-0.838, 0.305]
Secondary
Regulatory T Cell (%CD4) at Week 24 and Week 52
Regulatory T cell (%CD4) = CD4+ CD25hi IL-7Rlo (% of CD4+). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Regulatory T Cell (%CD4) at Week 24 and Week 52 | Week 52; n= 11, 10 | 5.0 Percentage of Regulatory T cell | Standard Error 1.01 |
| Placebo | Regulatory T Cell (%CD4) at Week 24 and Week 52 | Week 24; n= 9, 7 | 4.4 Percentage of Regulatory T cell | Standard Error 1.12 |
| Belimumab 10mg/kg | Regulatory T Cell (%CD4) at Week 24 and Week 52 | Week 52; n= 11, 10 | 4.4 Percentage of Regulatory T cell | Standard Error 1.04 |
| Belimumab 10mg/kg | Regulatory T Cell (%CD4) at Week 24 and Week 52 | Week 24; n= 9, 7 | 4.6 Percentage of Regulatory T cell | Standard Error 1.25 |
95% CI: [-3.2, 3.5]
95% CI: [-3.5, 2.3]
Secondary
Regulatory T Cell Count at Week 24 and Week 52
Regulatory T cell count is CD4+ CD25hi IL-7Rlo (Conc-cells/mL). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Regulatory T Cell Count at Week 24 and Week 52 | Week 24; n= 9, 7 | 23586.2 cells/mL | Standard Error 8427.77 |
| Placebo | Regulatory T Cell Count at Week 24 and Week 52 | Week 52; n= 10, 8 | 33038.7 cells/mL | Standard Error 7676.99 |
| Belimumab 10mg/kg | Regulatory T Cell Count at Week 24 and Week 52 | Week 24; n= 9, 7 | 24234.5 cells/mL | Standard Error 9238.41 |
| Belimumab 10mg/kg | Regulatory T Cell Count at Week 24 and Week 52 | Week 52; n= 10, 8 | 27419.8 cells/mL | Standard Error 9093.84 |
95% CI: [-24661.1, 25957.7]
95% CI: [-29994.8, 18757]
Secondary
Transitional B Cells Count at Week 24 and Week 52
Transitional B cell count (Newell) is CD19+CD24b+CD38b+IgD+ (Conc-cells/mL). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Transitional B Cells Count at Week 24 and Week 52 | Week 24; n=9, 7 | 5470 cells/mL | Standard Error 2910.9 |
| Placebo | Transitional B Cells Count at Week 24 and Week 52 | Week 52; n=10, 8 | 7110 cells/mL | Standard Error 2836.7 |
| Belimumab 10mg/kg | Transitional B Cells Count at Week 24 and Week 52 | Week 52; n=10, 8 | 6652 cells/mL | Standard Error 3291.5 |
| Belimumab 10mg/kg | Transitional B Cells Count at Week 24 and Week 52 | Week 24; n=9, 7 | 2679 cells/mL | Standard Error 3518.4 |
95% CI: [-12105, 6524]
95% CI: [-9487, 8572]
Secondary
Transitional B Cells Percentage at Week 24 and Week 52
Transitional B cell percentage (Newell) is CD19+CD24b+CD38b+IgD+ (%CD19+). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time frame: Week 24 and Week 52
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Transitional B Cells Percentage at Week 24 and Week 52 | Week 24; n=9, 7 | 2.43 Percentage of transitional B cells | Standard Error 0.776 |
| Placebo | Transitional B Cells Percentage at Week 24 and Week 52 | Week 52; n=11, 10 | 2.61 Percentage of transitional B cells | Standard Error 0.713 |
| Belimumab 10mg/kg | Transitional B Cells Percentage at Week 24 and Week 52 | Week 24; n=9, 7 | 1.14 Percentage of transitional B cells | Standard Error 0.869 |
| Belimumab 10mg/kg | Transitional B Cells Percentage at Week 24 and Week 52 | Week 52; n=11, 10 | 3.41 Percentage of transitional B cells | Standard Error 0.731 |
95% CI: [-3.59, 1.01]
95% CI: [-1.24, 2.82]