Systemic Lupus Erythematosus
Conditions
Keywords
Pediatric, Belimumab, Pharmacokinetics, Active Systemic Lupus Erythematosus, Safety, Efficacy
Brief summary
This study will be conducted to evaluate the safety, efficacy and pharmacokinetics of belimumab administered in combination with background standard therapy in pediatric participants with active SLE.
Interventions
DRUGBelimumab
Belimumab will be administered.
DRUGStandard therapy
Standard therapy will be continued.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Participants have or have had in series, 4 or more of the American College of Rheumatology (ACR) 11 criteria for the classification of SLE. * Participant's age is 5 to 17 years at the time of informed consent. * Have active SLE disease defined as a SELENA SLEDAI score \>= 8 at screening (SELENA SLEDAI scoring). * Have unequivocally positive autoantibody test results defined as an anti-nuclear antibody (ANA) titer \>=1:80 and/or a positive anti-Double stranded deoxyribonucleic acid (dsDNA) serum antibody test. * Are on a stable SLE therapy at Baseline. The stable treatment at Baseline consists of corticosteroids, anti-malarials, immunosuppressive/immunomodulatory agents and Non-steroidal anti-inflammatory drugs (NSAIDs), alone or in combination, at a fixed dose for a period of at least 30 days prior to Day 0. * No gender restriction. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * The investigator, or a person designated by the investigator, will obtain written informed assent from each study participant or the participant's legally acceptable representative, parent(s), or legal guardian and the participant's assent, when applicable, before any study-specific activity is performed. The investigator will retain the original copy of each participant's signed assent document.
Exclusion criteria
* Have an estimated glomerular filtration rate (eGFR) as calculated by Schwartz Formula of less than 30 mL/minutes. * Have acute severe nephritis defined as a significant worsening of renal disease (for example \[e.g.\], the presence of urinary sediments and other lab abnormalities) that, in the opinion of the study investigator, may lead to the participant requiring induction therapy with intravenous (IV) cyclophosphamide, Mycophenolate mofetil (MMF) or high dose corticosteroids during the first 6 months of the study. * Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant. * Have clinical evidence of significant, unstable or uncontrolled, acute or chronic diseases not due to SLE (cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases) which, in the opinion of the investigator, could confound the results of the study or put the participant at undue risk. * Have a planned surgical procedure or a history of any other medical disease (e.g., cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the investigator, makes the participant unsuitable for the study. * Have a history of malignant neoplasm within the last 5 years. * Have a history of a primary immunodeficiency. * Have an Immunoglobulin A (IgA) deficiency (IgA level less than \[\<\]10 mg/deciliters \[milligrams/dL\]). * Have acute or chronic infections requiring management. * Have recent infections that, in the opinions of the investigator, makes the participant unsuitable for the study or could put the participant at undue risk. * Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 0. * Have a Grade 3 or greater laboratory abnormality based on the protocol toxicity scale except for the following that are allowed: 1. Stable Grade 3 prothrombin time (PT) secondary to warfarin treatment. 2. Stable Grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and not related to liver disease or anti-coagulant therapy. 3. Stable Grade 3 hypoalbuminemia due to lupus nephritis and not related to liver disease or malnutrition. 4. Any grade proteinuria 5. Stable Grade 3 gamma glutamyl transferase (GGT) elevation due to lupus hepatitis and not related to alcoholic liver disease, uncontrolled diabetes or viral hepatitis. If present, any abnormalities in the Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) must be Grade 2. 6. Stable Grade 3 neutropenia; or stable Grade 3 lymphopenia; or stable Grade 3 leukopenia, due to SLE * Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies. * Have evidence of serious suicide risk including any history of suicidal behavior in the last 6 months or who in the investigator's judgment, poses a significant suicide risk. * Have received treatment with belimumab at any time. * Have received any of the following within 364 days of Day 0: 1. Treatment with any B-cell targeted 2. Abatacept 3. A biologic investigational agent * Have required 3 or more courses of systemic corticosteroids for concomitant conditions (e.g., asthma, atopic dermatitis) within 90 days of Day 0. * Have received any of the following within 90 days of Day 0: 1. Anti-Tumour Necrosis Factor (TNF) or anti-interleukin (IL)-6 therapy (e.g., adalimumab, etanercept, infliximab, tocilizumab certolizumab, golimumab) 2. Interleukin-1 receptor antagonist (anakinra) 3. Intravenous immunoglobulin (IVIG) 4. Plasmapheresis * Have received any of the following within 30 days of Day 0: 1. IV cyclophosphamide 2. A non-biologic investigational agent (30 days window OR 5 half-lives, whichever is longer) 3. Any new immunosuppressive/immunomodulatory agent, anti-malarial, NSAID 4. High dose prednisone or equivalent (\>1.5 mg/kilogram/day) or any intramuscular or intravenous steroid injection. * Have received a live or live-attenuated vaccine within 30 days of Day 0. * Have active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident \[CVA\], cerebritis or CNS vasculitis) requiring therapeutic intervention within 60 days of Day 0. * Have required renal replacement therapy (e.g., hemodialysis, peritoneal dialysis) within 90 days of Day 0 or be currently on renal replacement therapy. * Participation in an interventional clinical study either concurrently or within 6 months of screening. Participation in an observational study may be permitted. * Have a historically positive test or test positive at screening for Human immunodeficiency virus (HIV) antibody. * Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (posteroanterior) and a positive (not indeterminate) QuantiFERON-TB Gold Plus test. * Hepatitis B: Serologic evidence of Hepatitis B (HB) infection defined as Hepatitis B surface antigen positive (HBsAg+) or Hepatitis B core antibody positive (HBcAb+). * Hepatitis C: Positive test for Hepatitis C antibody at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Greater Than Equal to (>=) 4 Points Reduction From Baseline to Week 52 in Safety of Estrogen in Lupus National Assessment - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | Baseline (Day 0) and Week 52 | The SELENA-SLEDAI score is a cumulative and weighted index for assessing SLE disease activity in participants with SLE. It consists of 24 disease descriptors related to signs and symptoms, laboratory tests, and physician's assessment across 9 organ systems. Each descriptor is assigned a weighted score (8 descriptors with a weight of 8 each, 6 descriptors with a weight of 4 each, 7 descriptors with a weight of 2 each, and 3 descriptors with a weight of 1 each) which is added up if the descriptor is observed during a visit or within the preceding 10 days. The total score ranges from 0 (no disease activity) to 105 (all 24 descriptors present simultaneously). A higher score indicates a more significant degree of disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Number of participants with a decrease of 4 points or more in the score at Week 52 compared to their Baseline score is presented. |
| Number of Participants With Adverse Events of Special Interest (AESIs) Through Week 52 | Up to Week 52 | An adverse event (AE) is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs included malignancies, post-infusion systemic or hypersensitivity reactions, infections (including serious infections of special interest), and depression, suicide, or self-injury. Infections of special interest included opportunistic infections (OI), herpes zoster (HZ), tuberculosis (TB), and sepsis. Number of participants with AESIs as identified by custom Medical Dictionary for Regulatory Activities (MedDRA) query has been reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal Half-life (t1/2) of Belimumab | Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84 | Blood samples were collected at indicated time points for PK analysis of belimumab. |
| Maximum Plasma Concentration (Cmax) of Belimumab at Steady State | Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84 | Blood samples were collected at indicated time points for PK analysis of belimumab. |
| Minimum Plasma Concentration Reached Prior to Administration of Next Dose (Cmin) of Belimumab at Steady State | Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84 | Blood samples were collected at indicated time points for PK analysis of belimumab. |
| Average Plasma Concentration (Cavg) of Belimumab at Steady State | Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84 | Blood samples were collected at indicated time points for PK analysis of belimumab. |
| Area Under the Concentration Curve (AUC) of Belimumab at Steady State | Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84 | Blood samples were collected at indicated time points for PK analysis of belimumab. |
| Number of Participants With AEs and Serious Adverse Events (SAEs) Through Week 52 | Up to Week 52 | An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a birth defect or congenital anomaly, or other situations as per the medical or scientific judgment of the investigator. Number of participants with AEs and SAEs has been reported. |
| Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit | Baseline (Day 0) and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | The SELENA-SLEDAI score is a cumulative and weighted index for assessing SLE disease activity in participants with SLE. It consists of 24 disease descriptors related to signs and symptoms, laboratory tests, and physician's assessment across 9 organ systems. Each descriptor is assigned a weighted score (8 descriptors with a weight of 8 each, 6 descriptors with a weight of 4 each, 7 descriptors with a weight of 2 each, and 3 descriptors with a weight of 1 each) which is added up if the descriptor is observed during a visit or within the preceding 10 days. The total score ranges from 0 (no disease activity) to 105 (all 24 descriptors present simultaneously). A higher score indicates a more significant degree of disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Percentage of participants with a decrease of 4 points or more in the score at each visit compared to their Baseline score is presented. |
| Change From Baseline to Week 52 in Physician Global Assessment (PGA) | Baseline (Day 0) and Week 52 | The PGA is used to assess the participant's current disease activity by investigator. It is collected on a 10 centimeter (cm) visual analogue scale. The score ranges from 0 (no activity) to 3 (severe activity). Lower score means no disease activity, higher score means severe disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. |
| Change From Baseline to Week 52 in Parent Global Assessment (ParentGA) | Baseline (Day 0) and Week 52 | The ParentGA is used to assess the participant's overall well-being at the moment rated on a 21-numbered circle visual analog scale by the parent. The score ranges from 0 (very well) to 10 (very poorly). Higher score indicates worse effect of the illness on the child. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. |
| Change From Baseline in Average Daily Prednisone Equivalent Dose at Week 52 | Baseline (Day 0) and Week 52 | The average daily prednisone equivalent dose accounted for all steroids taken IV, intramuscularly (IM), subcutaneously (SC), intradermally, and orally for both SLE and non-SLE reasons. All steroid dosages were converted to a prednisone equivalent in mg at each visit. The daily prednisone equivalent dose for a steroid was calculated as follows: collected dose of the steroid in mg multiplied by (\*) conversion factor \* frequency factor. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. At Baseline, the average daily prednisone equivalent dose was the sum of all prednisone doses over 7 consecutive days up to but not including Day 0, divided by 7. The average daily prednisone dose at Week 52 visit was the sum of all prednisone doses over 7 consecutive days up to and including the Week 52 visit, divided by 7. Average daily prednisone equivalent dose was expressed in milligrams per day. |
| Time to First Flare Over 52 Weeks | Up to Week 52 | The SLE flare index (SFI) is used to categorize SLE flares as mild/moderate or severe. A mild/moderate SFI flare involves: a SELENA-SLEDAI score increase of 3 to 12 points (higher score means greater disease activity); SLE symptom development; prednisone dose increase (but not above 0.5 milligrams per kilogram per day \[mg/kg/day\]); non-steroidal anti-inflammatory drugs (NSAIDs)/hydroxychloroquine addition; or PGA score increase by 1 or more, but not to more than 2.5 (higher score means greater disease activity). A severe SFI flare involves: SELENA-SLEDAI score increase over 12 points; onset or worsening of severe SLE symptoms; prednisone dose increase above 0.5 mg/kg/day; introduction of potent immunosuppressants; hospitalization; or PGA score reaching 2.5 or higher. Time to first SLE flare (mild/moderate or severe) was the number of days from treatment start date until the participant met an event. Time to first flare was defined as event date minus treatment start date plus 1. |
| Time to First Severe Flare Over 52 Weeks | Up to Week 52 | The SFI is used to categorize SLE flares as mild/moderate or severe. A severe SFI flare involves SELENA-SLEDAI score increase over 12 points (higher score means greater disease activity), onset or worsening of severe SLE symptoms, prednisone dose increase above 0.5 mg/kg/day, introduction of potent immunosuppressants, hospitalization, or PGA score reaching 2.5 or higher (higher score means higher disease activity). Time to first severe SLE flare was the number of days from treatment start date until the participant met an event. Time to first severe flare was defined as event date minus treatment start date plus 1. |
| Median Belimumab Concentration Levels at Day 0, 7, and 14 Days Post First Dose, and Pre-infusion and Post-infusion at Day 84 | Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84 | Blood samples were collected at indicated time points for measurement of plasma concentrations of belimumab. |
| Apparent Total Clearance of Belimumab | Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84 | Blood samples were collected at indicated time points for PK analysis of belimumab. |
| Volume of Distribution of Belimumab | Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84 | Blood samples were collected at indicated time points for PK analysis of belimumab. |
Countries
China
Contacts
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Belimumab Participants with active SLE received belimumab at 10 mg/kg body weight by IV infusion over a minimum of 1 hour on Days 0, 14, 28, and then every 28 days through Week 48 in combination with standard therapy. | 67 |
| Total | 67 |
Baseline characteristics
| Characteristic | Belimumab |
|---|---|
| Age, Continuous | 13.0 YEARS STANDARD_DEVIATION 2.22 |
| Race/Ethnicity, Customized Asian | 67 Participants |
| Sex: Female, Male Female | 51 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 67 |
| other Total, other adverse events | 57 / 67 |
| serious Total, serious adverse events | 20 / 67 |
Outcome results
Primary
Number of Participants With Adverse Events of Special Interest (AESIs) Through Week 52
An adverse event (AE) is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs included malignancies, post-infusion systemic or hypersensitivity reactions, infections (including serious infections of special interest), and depression, suicide, or self-injury. Infections of special interest included opportunistic infections (OI), herpes zoster (HZ), tuberculosis (TB), and sepsis. Number of participants with AESIs as identified by custom Medical Dictionary for Regulatory Activities (MedDRA) query has been reported.
Time frame: Up to Week 52
Population: Intent-to-Treat (ITT) population consisted of all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Belimumab | Number of Participants With Adverse Events of Special Interest (AESIs) Through Week 52 | All malignancies | 0 Participants |
| Belimumab | Number of Participants With Adverse Events of Special Interest (AESIs) Through Week 52 | All infections of special interest (OI, HZ, TB, sepsis) | 2 Participants |
| Belimumab | Number of Participants With Adverse Events of Special Interest (AESIs) Through Week 52 | Depression (including mood disorders and anxiety)/suicide/self-injury | 0 Participants |
| Belimumab | Number of Participants With Adverse Events of Special Interest (AESIs) Through Week 52 | Post-infusion systemic reactions (PISR) | 0 Participants |
Primary
Number of Participants With Greater Than Equal to (>=) 4 Points Reduction From Baseline to Week 52 in Safety of Estrogen in Lupus National Assessment - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score
The SELENA-SLEDAI score is a cumulative and weighted index for assessing SLE disease activity in participants with SLE. It consists of 24 disease descriptors related to signs and symptoms, laboratory tests, and physician's assessment across 9 organ systems. Each descriptor is assigned a weighted score (8 descriptors with a weight of 8 each, 6 descriptors with a weight of 4 each, 7 descriptors with a weight of 2 each, and 3 descriptors with a weight of 1 each) which is added up if the descriptor is observed during a visit or within the preceding 10 days. The total score ranges from 0 (no disease activity) to 105 (all 24 descriptors present simultaneously). A higher score indicates a more significant degree of disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Number of participants with a decrease of 4 points or more in the score at Week 52 compared to their Baseline score is presented.
Time frame: Baseline (Day 0) and Week 52
Population: ITT population consisted of all participants who received at least one dose of study treatment. One participant with Baseline SELENA-SLEDAI score less than 4 was excluded from the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Belimumab | Number of Participants With Greater Than Equal to (>=) 4 Points Reduction From Baseline to Week 52 in Safety of Estrogen in Lupus National Assessment - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score | 44 Participants |
Secondary
Apparent Total Clearance of Belimumab
Time frame: Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84
Secondary
Area Under Plasma Concentration-time Curve (AUC) of Belimumab at Steady State
Time frame: Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84
Secondary
Change From Baseline in Average Daily Prednisone Equivalent Dose at Week 52
The average daily prednisone equivalent dose accounted for all steroids taken IV, intramuscularly (IM), subcutaneously (SC), intradermally, and orally for both SLE and non-SLE reasons. All steroid dosages were converted to a prednisone equivalent in mg at each visit. The daily prednisone equivalent dose for a steroid was calculated as follows: collected dose of the steroid in mg multiplied by (\*) conversion factor \* frequency factor. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. At Baseline, the average daily prednisone equivalent dose was the sum of all prednisone doses over 7 consecutive days up to but not including Day 0, divided by 7. The average daily prednisone dose at Week 52 visit was the sum of all prednisone doses over 7 consecutive days up to and including the Week 52 visit, divided by 7. Average daily prednisone equivalent dose was expressed in milligrams per day.
Time frame: Baseline (Day 0) and Week 52
Population: ITT population consisted of all participants who received at least one dose of study treatment. 'Overall Number of Participants Analyzed' included only those participants who were analyzed (i.e., contributed data reported in table).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Belimumab | Change From Baseline in Average Daily Prednisone Equivalent Dose at Week 52 | -6.020 milligrams per day | Standard Deviation 9.297 |
Secondary
Change From Baseline to Week 52 in Parent Global Assessment (ParentGA)
The ParentGA is used to assess the participant's overall well-being at the moment rated on a 21-numbered circle visual analog scale by the parent. The score ranges from 0 (very well) to 10 (very poorly). Higher score indicates worse effect of the illness on the child. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Baseline (Day 0) and Week 52
Population: ITT population consisted of all participants who received at least one dose of study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Belimumab | Change From Baseline to Week 52 in Parent Global Assessment (ParentGA) | -2.71 Scores on scale | Standard Deviation 2.713 |
Secondary
Change From Baseline to Week 52 in Physician Global Assessment (PGA)
The PGA is used to assess the participant's current disease activity by investigator. It is collected on a 10 centimeter (cm) visual analogue scale. The score ranges from 0 (no activity) to 3 (severe activity). Lower score means no disease activity, higher score means severe disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time frame: Baseline (Day 0) and Week 52
Population: ITT population consisted of all participants who received at least one dose of study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Belimumab | Change From Baseline to Week 52 in Physician Global Assessment (PGA) | -0.931 Scores on scale | Standard Deviation 0.6046 |
Secondary
Estimated Average Concentration (Cavg) of Belimumab at Steady State
Time frame: Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84
Secondary
Estimated Maximum Concentration (Cmax) of Belimumab at Steady State
Time frame: Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84
Secondary
Estimated Minimum Concentration (Cmin) of Belimumab at Steady State
Time frame: Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84
Secondary
Median Belimumab Concentration Levels at Day 0, 7, and 14 Days Post First Dose, and Pre-infusion and Post-infusion at Day 84
Blood samples were collected at indicated time points for measurement of plasma concentrations of belimumab.
Time frame: Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84
Population: Pharmacokinetic (PK) population consisted of all the participants who received at least one dose of study treatment and for whom at least one post belimumab treatment PK sample was obtained and analyzed. 'Overall number of participants analyzed' included only those participants who were analyzed (i.e., contributed data reported in table). 'Number analyzed' included participants evaluable for specified time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Belimumab | Median Belimumab Concentration Levels at Day 0, 7, and 14 Days Post First Dose, and Pre-infusion and Post-infusion at Day 84 | Day 0 | 197.1173 Micrograms per milliliter |
| Belimumab | Median Belimumab Concentration Levels at Day 0, 7, and 14 Days Post First Dose, and Pre-infusion and Post-infusion at Day 84 | Day 7 | 71.3616 Micrograms per milliliter |
| Belimumab | Median Belimumab Concentration Levels at Day 0, 7, and 14 Days Post First Dose, and Pre-infusion and Post-infusion at Day 84 | Day 14 | 37.8585 Micrograms per milliliter |
| Belimumab | Median Belimumab Concentration Levels at Day 0, 7, and 14 Days Post First Dose, and Pre-infusion and Post-infusion at Day 84 | Day 84, pre-infusion | 28.2415 Micrograms per milliliter |
| Belimumab | Median Belimumab Concentration Levels at Day 0, 7, and 14 Days Post First Dose, and Pre-infusion and Post-infusion at Day 84 | Day 84, post-infusion | 238.5688 Micrograms per milliliter |
Secondary
Number of Participants With AEs and Serious Adverse Events (SAEs) Through Week 52
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a birth defect or congenital anomaly, or other situations as per the medical or scientific judgment of the investigator. Number of participants with AEs and SAEs has been reported.
Time frame: Up to Week 52
Population: ITT population consisted of all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Belimumab | Number of Participants With AEs and Serious Adverse Events (SAEs) Through Week 52 | AEs | 56 Participants |
| Belimumab | Number of Participants With AEs and Serious Adverse Events (SAEs) Through Week 52 | SAEs | 19 Participants |
Secondary
Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit
The SELENA-SLEDAI score is a cumulative and weighted index for assessing SLE disease activity in participants with SLE. It consists of 24 disease descriptors related to signs and symptoms, laboratory tests, and physician's assessment across 9 organ systems. Each descriptor is assigned a weighted score (8 descriptors with a weight of 8 each, 6 descriptors with a weight of 4 each, 7 descriptors with a weight of 2 each, and 3 descriptors with a weight of 1 each) which is added up if the descriptor is observed during a visit or within the preceding 10 days. The total score ranges from 0 (no disease activity) to 105 (all 24 descriptors present simultaneously). A higher score indicates a more significant degree of disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Percentage of participants with a decrease of 4 points or more in the score at each visit compared to their Baseline score is presented.
Time frame: Baseline (Day 0) and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Population: ITT population. 1 participant with Baseline SELENA-SLEDAI score below 4 was excluded. All 66 participants served as denominator to calculate percentages at each visit. For all visits except Week 52 (where percentage value was rounded off as no data was missing), missing data from missed visits were handled by multiple imputation. Estimates generated for every imputed dataset were combined by Rubin's rules to obtain percentages. So reported percentages may not yield whole number of participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Belimumab | Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit | Week 20 | 65.4 Percentage of Participants |
| Belimumab | Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit | Week 28 | 65.7 Percentage of Participants |
| Belimumab | Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit | Week 4 | 39.8 Percentage of Participants |
| Belimumab | Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit | Week 8 | 51.8 Percentage of Participants |
| Belimumab | Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit | Week 12 | 68.9 Percentage of Participants |
| Belimumab | Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit | Week 16 | 69.0 Percentage of Participants |
| Belimumab | Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit | Week 24 | 68.1 Percentage of Participants |
| Belimumab | Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit | Week 32 | 67.7 Percentage of Participants |
| Belimumab | Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit | Week 36 | 69.1 Percentage of Participants |
| Belimumab | Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit | Week 40 | 75.1 Percentage of Participants |
| Belimumab | Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit | Week 44 | 74.2 Percentage of Participants |
| Belimumab | Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit | Week 48 | 71.3 Percentage of Participants |
| Belimumab | Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit | Week 52 | 66.7 Percentage of Participants |
Secondary
Terminal Half-life (t1/2) of Belimumab
Time frame: Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84
Secondary
Time to First Flare Over 52 Weeks
The SLE flare index (SFI) is used to categorize SLE flares as mild/moderate or severe. A mild/moderate SFI flare involves: a SELENA-SLEDAI score increase of 3 to 12 points (higher score means greater disease activity); SLE symptom development; prednisone dose increase (but not above 0.5 milligrams per kilogram per day \[mg/kg/day\]); non-steroidal anti-inflammatory drugs (NSAIDs)/hydroxychloroquine addition; or PGA score increase by 1 or more, but not to more than 2.5 (higher score means greater disease activity). A severe SFI flare involves: SELENA-SLEDAI score increase over 12 points; onset or worsening of severe SLE symptoms; prednisone dose increase above 0.5 mg/kg/day; introduction of potent immunosuppressants; hospitalization; or PGA score reaching 2.5 or higher. Time to first SLE flare (mild/moderate or severe) was the number of days from treatment start date until the participant met an event. Time to first flare was defined as event date minus treatment start date plus 1.
Time frame: Up to Week 52
Population: ITT population consisted of all participants who received at least one dose of study treatment. 'Overall number of participants analyzed' included those participants who experienced a post-baseline SFI flare over 52 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Belimumab | Time to First Flare Over 52 Weeks | 141.0 days |
Secondary
Time to First Severe Flare Over 52 Weeks
The SFI is used to categorize SLE flares as mild/moderate or severe. A severe SFI flare involves SELENA-SLEDAI score increase over 12 points (higher score means greater disease activity), onset or worsening of severe SLE symptoms, prednisone dose increase above 0.5 mg/kg/day, introduction of potent immunosuppressants, hospitalization, or PGA score reaching 2.5 or higher (higher score means higher disease activity). Time to first severe SLE flare was the number of days from treatment start date until the participant met an event. Time to first severe flare was defined as event date minus treatment start date plus 1.
Time frame: Up to Week 52
Population: ITT population consisted of all participants who received at least one dose of study treatment. 'Overall number of participants analyzed' included those participants who experienced a post-baseline severe SFI flare over 52 weeks.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Belimumab | Time to First Severe Flare Over 52 Weeks | NA days |
Secondary
Volume of Distribution of Belimumab
Time frame: Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84