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A Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination With Rituximab to Adult Subjects With Systemic Lupus Erythematosus (SLE) - BLISS-BELIEVE

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03312907
Recruitment Status : Completed
First Posted : October 18, 2017
Results First Posted : April 25, 2022
Last Update Posted : April 25, 2022
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE October 13, 2017
First Posted Date  ICMJE October 18, 2017
Results First Submitted Date  ICMJE March 25, 2022
Results First Posted Date  ICMJE April 25, 2022
Last Update Posted Date April 25, 2022
Actual Study Start Date  ICMJE March 1, 2018
Actual Primary Completion Date May 29, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 25, 2022)
Percentage of Participants With a State of Disease Control at Week 52 [ Time Frame: Week 52 ]
Percentage of participants with a state of disease control (Independent blinded assessor [IBA]) was defined as the percentage of participants with a Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K)score less than or equal to(<=)2 achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day at Week 52. SLEDAI-2K was a weighted, cumulative index for measuring systemic lupus erythematosus (SLE) disease activity in previous 10 days,consisting 24 individual items in which signs and symptoms, laboratory tests and physician's assessment for each item within each of 9 organ systems were given a weighted score(1 to 8 with higher score indicating increased activity)and summed if present at the time of visit or in preceding 10 days. The SLEDAI-2K score was sum of all 24 individual items from the SLEDAI-2K, ranges from 0(no symptoms) to 105(presence of all defined symptoms) with higher scores representing increased disease activity.
Original Primary Outcome Measures  ICMJE
 (submitted: October 13, 2017)
Proportion of subjects with a state of disease control at week 52 [ Time Frame: Week 52 ]
State of disease control defined as SLEDAI-2K score <=2, achieved without the use of immunosuppressant and with corticosteroids at a prednisone equivalent dose of <=5 milligram per day (mg/day). The SLEDAI-2K is a clinical index for measuring SLE disease activity
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2022)
  • Percentage of Participants With a State of Clinical Remission at Week 64 [ Time Frame: Week 64 ]
    Percentage of participants with a state of clinical remission (IBA) was defined as percentage of participants with a clinical SLEDAI-2K score =0 (does not include anti-double stranded deoxyribonucleic [dsDNA] and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day at Week 64. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days, consisting 24 individual items in which signs and symptoms, laboratory tests, and physician's assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity.
  • Percentage of Participants With a State of Disease Control at Week 104 [ Time Frame: Week 104 ]
    Percentage of participants with a state of disease control (IBA) was defined as the percentage of participants with a SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day at Week 104. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days which consisted of 24 individual items in which signs and symptoms, laboratory tests, and physician's assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity.
  • Percentage of Participants With a State of Disease Control by Visits [ Time Frame: Weeks 12, 26, 40, 52, 64, 80 and 104 ]
    Percentage of participants with a state of disease control (IBA) was defined as the percentage of participants with a SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days which consisted of 24 individual items in which signs and symptoms, laboratory tests, and physician's assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity.
  • Percentage of Participants With a State of Clinical Remission by Visits [ Time Frame: Weeks 64, 80 and 104 ]
    Percentage of participants with a state of clinical remission (IBA) was defined as percentage of participants with a clinical SLEDAI-2K score =0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days, consisting 24 individual items in which signs and symptoms, laboratory tests, and physician's assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity
  • Percentage of Participants With a State of Complete Remission (CR) Sustained for at Least 24 Weeks During Week 52 to Week 104 [ Time Frame: Week 52 to Week 104 ]
    Percentage of participants with a state of CR (Principal Investigator [PI] assessed) was defined as percentage of participants with a SLEDAI-2K=0 achieved without immunosuppressants and with corticosteroids at prednisone equivalent dose of 0 mg/day,sustained for at least 24 weeks. Sustained CR was longest period a participant maintains CR without break calculated as last consecutive CR date minus first consecutive CR date plus 1. SLEDAI-2K consisted of 24 individual items within each 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at time of visit or in preceding 10 days. SLEDAI-2K score was sum of all 24 individual items from SLEDAI-2K, ranges from 0(no symptoms) to 105(presence of all defined symptoms),higher scores indicates increased disease activity. Percentage of participants with a state of CR sustained for at least 24 weeks at any visit during Week 52 to Week 104 were reported.
  • Percentage of Participants With a State of Clinical Remission (CLR) Sustained for at Least 24 Weeks From Week 80 to Week 104 [ Time Frame: From Week 80 to Week 104 ]
    Percentage of participants with a state of CLR (PI assessed) at Week 104 was defined as percentage of participants with a clinical SLEDAI-2K score=0 (does not include anti-dsDNA and complement activity scores) achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day, sustained for at least 24 weeks(from Week 80 to Week 104). Sustained CLR is longest period a participant maintains CLR without a break, calculated as last consecutive CLR date minus first consecutive CLR date plus 1. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score(1 to 8 with higher score indicating increased activity) and summed if present at the time of visit or in preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity.
  • Percentage of Participants With a State of Complete Remission by Visits [ Time Frame: Weeks 60, 64, 72, 80, 88, 96 and 104 ]
    Percentage of participants with a state of complete remission (PI assessed) was defined as the percentage of participants with a SLEDAI-2K score =0, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. SLEDAI-2K was a weighted, cumulative index for measuring systemic lupus erythematosus (SLE) disease activity in the previous 10 days which consisted of 24 individual items in which signs and symptoms, laboratory tests, and physician's assessment for each item within for each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity.
  • Time to First Severe Flare [ Time Frame: Up to Week 104 ]
    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 to first severe flare was measured by Modified SLE flare index which identifies whether a participant had experienced a mild/moderate or severe flare. Analysis of first severe flare was performed on the modified SLE Flare index that excludes severe flares that were triggered only by an increase is SLEDAI-2K score to greater than 12.
  • Time to First Flare [ Time Frame: Up to Week 104 ]
    Time to first SLE flare 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 flare was measured by modified SLE flare index which identifies whether a participant had experienced a mild/moderate or severe flare.
  • Time to Disease Control Sustained for at Least 24 Weeks and Maintained Through Week 104 [ Time Frame: Up to Week 104 ]
    Disease control sustained for at least 24 weeks and maintained through Week 104 was defined as SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day. Time to disease control (PI assessed) was defined as the first visit of sustained disease control until Week 104 on or before Week 80 minus treatment start date (Day 1) plus 1. Sustained disease control was longest period a participant maintained disease control without a break. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. SLEDAI-2K score was the sum of all 24 individual items from SLEDAI-2K , ranges from 0 (no symptoms) to 105 (presence of all defined symptoms),higher scores representing increased disease activity.
  • Time to Clinical Remission Sustained for at Least 24 Weeks and Maintained Through Week 104 [ Time Frame: Up to Week 104 ]
    Clinical remission sustained for at least 24 weeks and maintained through Week 104 was defined as clinical SLEDAI-2K score=0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. Time to CLR (PI assessed) was defined as first visit of sustained CLR until Week 104 on or before Week 80 minus treatment start date (Day 1) plus 1. Sustained CLR was longest period a participant maintained clinical remission without a break. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity.
  • Duration of Disease Control [ Time Frame: Up to Week 104 ]
    Duration of disease control was defined as SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day. The duration of disease control (PI assessed) was the longest period between 2 visits that the participant was a disease control responder at all visits and calculated as the first visit of disease control minus last visit of disease control plus 1. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. SLEDAI-2K score was the sum of all 24 individual items from SLEDAI-2K, ranges from 0(no symptoms) to 105 (presence of all defined symptoms),higher scores representing increased disease activity
  • Duration of Clinical Remission [ Time Frame: Up to Week 104 ]
    Clinical remission was defined as clinical SLEDAI-2K score =0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. The duration of clinical remission (PI assessed) was the longest period between 2 visits that the participant was a clinical remission responder at all visits and was calculated as the first visit of clinical remission minus last visit of clinical remission plus 1. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity.
  • Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Score by Visit (PI Assessed) [ Time Frame: Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104 ]
    The SLEDAI-2K consisted of 24 individual items within 9 organ systems. Each item was given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of visit or in the preceding 10 days. Weighted scores for central nervous system (CNS) (7 items) was 8; for vascular (1 item) was 8; for Musculoskeletal (2 items) was 4; for Renal (4 items) was 4; for Mucocutaneous (3 items) was 2; for Cardiovascular and Respiratory (2 items) was 2; for Immunologic (2 items) was 2;for Constitutional (1 item) was 1 and for Hematologic (2 items) was 1. SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. Baseline value was latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Percentage of Participants With SLEDAI-2K Organ Improvement Compared to Baseline by Visits (PI Assessed) [ Time Frame: Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104 ]
    SLEDAI-2K assessments consisted of 24 individual items with 9 organ systems. Each item was given a weighted score(1 to 8 with higher score indicating increased activity)and summed if present at the time of analysis. SLEDAI-2K score was sum of all 24 individual items from SLEDAI-2K ranges from 0(no symptoms) to 105(presence of all defined symptoms). Higher scores indicates increased disease activity. An improvement was defined as a decrease(compared to Baseline) in SLEDAI-2K score within same organ system at a post-Baseline visit. Baseline value was latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data for following organ systems was reported: CNS total, Vascular total, Musculoskeletal total, Renal total, Mucocutaneous total, Cardiovascular (Cardio) and Respiratory (Resp) total, Immunologic total and Hematologic total. Constitutional organ system was removed from analysis and its one item (fever)moved to hematologic organ system.
  • Percentage of Participants With SLEDAI-2K Organ Worsening Compared to Baseline by Visits (PI Assessed) [ Time Frame: Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104 ]
    SLEDAI-2K assessments consisted of 24 individual items with 9 organ systems. Each item was given a weighted score(1 to 8 with higher score indicating increased activity)and summed if present at time of analysis. SLEDAI-2K score was sum of all 24 individual items from SLEDAI-2K, ranges from 0(no symptoms) to 105(presence of all defined symptoms). Higher scores indicates increased disease activity. A worsening was defined as an increase(compared to Baseline) in SLEDAI-2K score within same organ system at a post-Baseline visit. Baseline value was latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Percentage of participants with SLEDAI-2K organ worsening for following organ systems were reported;CNS total,Vascular total,Musculoskeletal total,Renal total,Mucocutaneous total,Cardio and Resp total,Immunologic total and Hematologic total. Constitutional organ system was removed from analysis and its one item (fever)moved to hematologic organ system.
  • Change From Baseline in Physician Global Assessment (PGA) by Visits [ Time Frame: Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104 ]
    The Physician's Global Assessment (PGA) was a physician-reported visual analogue scale that provides an overall measure of the participant's current disease activity. Physician's Global Assessment was collected on a 10 centimeter (cm) visual analogue scale (VAS) by placing a mark on the scale between 0 (no disease activity) to 10 (maximum disease activity). The PGA score was then rescaled for reporting by multiplying the collected score by 3 divided by 10. Hence, the PGA score ranges from 0 to 3 with higher scores indicating greater disease activity. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as the post-dose visit value minus Baseline value.
  • Percentage of Participants With Systemic Lupus International Collaborating Clinics (SLICC) -American College of Rheumatology (ACR) Damage Index Worsening Compared With Baseline at Week 52 and Week 104 [ Time Frame: Baseline (Day 1), Week 52 and Week 104 ]
    The SLICC-ACR Damage Index measures irreversible (not related to active inflammation) changes occurring since the diagnosis of SLE ascertained by clinical assessment and present for at least 6 months. The questionnaire contains 39 items covering 12 different organ systems which were scored on a numerical scale between 0 (no damage) to 7 (increasing disease damage). Individual ranges for organ systems were; ocular: 0-2, neuropsychiatric: 0-6, renal: 0-3, pulmonary: 0-5, cardiovascular:0-6, peripheral vascular: 0-5, gastrointestinal:0-5, musculoskeletal: 0-6, skin: 0-3, endocrine (diabetes): 0-1, gonadal:0-1 and malignancies: 0-2. The SLICC-ACR score was calculated by taking sum of the individual scores for 12 organ systems which ranges from 0 (no damage) to 45 (increasing disease damage) where higher score indicates increasing disease damage severity. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
  • Percentage of Participants That Met the Lupus Low Disease Activity State (LLDAS) Response Criteria by Visits (PI Assessed) [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96 and 104 ]
    Lupus low disease activity state (LLDAS) was defined as a state which, if sustained, was associated with a low likelihood of adverse outcome, considering disease activity and medication safety. The LLDAS response criteria were: (1) SLEDAI-2K <=4, with no activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity; (2) no new features of lupus disease activity compared with the previous assessment; (3) PGA (scale 0-3), <=1; (4) current prednisolone (or equivalent) dose <=7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents, excluding investigational drugs. Percentage of participants that met the LLDAS response criteria were reported.
  • Percentage of Participants With a State of Disease Control Using the PI Assessment of SLEDAI-2K by Visit [ Time Frame: Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104 ]
    Percentage of participants with a state of disease control was defined as the percentage of participants with a SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day, using the PI assessment of SLEDAI-2K. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. SLEDAI-2K score was the sum of all 24 individual items from SLEDAI-2K, ranges from 0 (no symptoms) to 105 (presence of all defined symptoms), higher scores representing increased disease activity. Percentage of participants with a state of disease control using the PI assessment of SLEDAI-2K were summarized.
  • Percentage of Participants With a State of Clinical Remission Using the PI Assessment of SLEDAI-2K by Visit [ Time Frame: Weeks 60, 64, 72, 80, 88, 96 and 104 ]
    Percentage of participants with a state of clinical remission was defined as the percentage of participants with a clinical SLEDAI-2K score =0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants (which was allowed in Belimumab+ Standard therapy arm only) and with corticosteroids at a prednisone equivalent dose of 0 mg/day using the PI assessment of SLEDAI-2K. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity. Percentage of participants with a state of clinical remission using the PI assessment of SLEDAI-2K were summarized.
  • Number of Participants With Serious Adverse Events (SAE) and Non-serious AE (Non-SAE) [ Time Frame: Up to Week 111 (including 8 weeks of safety follow-up) ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A 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 disability/incapacity, is a congenital anomaly/birth defect or any other situations as per medical or scientific judgment. Data for number of participants with SAE and non-SAE (>=5 %) has been summarized.
  • Number of Participants With Adverse Events of Special Interest (AESIs) [ Time Frame: Up to Week 104 ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. AESIs were Malignant Neoplasms, Post-Injection Systemic Reactions (PISR), All Infections of Special Interest (Opportunistic Infections (OI), Herpes Zoster (HZ), Tuberculosis (TB), and Sepsis), Depression (including mood disorders and anxiety)/suicide/self-injury and Deaths. Data for number of participants with AESIs has been summarized.
  • Change From Baseline in Patient Global Assessment (PtGA) by Visits [ Time Frame: Baseline (Day 1) and Weeks 8, 12, 26, 40, 52, 64, 72 and 104 ]
    The Patient's Global Assessment (PtGA) of Disease Activity is a single-item, participant reported scale developed for the assessment of the participant's overall rating of their disease activity due to SLE. The scale measures disease activity ranging from 0 (Very Well) to 10 (Very Poor) and the higher score indicates severe disease activity. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as the post-dose visit value minus Baseline value.
  • Change From Baseline in Lupus Quality of Life (LupusQoL) Domain Scores by Visit [ Time Frame: Baseline (Day 1) and Weeks 8, 12, 26, 40, 52, 64, 72 and 104 ]
    LupusQoL is a SLE-specific health related qualify of life (HRQOL) instrument with 34 questions across 8 domains:Physical health(8 items),Pain(3 items),Planning(3 items),Intimate relationship(2 items),Burden to others(3 items),Emotional health(6 items),Body image(5 items),Fatigue(4 items). Questions were related to participants experience in prior 4 weeks.A 5-point Likert response format was used, ranging from 0(all of the time) to 4(never) for each question. Individual domain scores were reported which were calculated by taking sum of responses to all items within each domain. Individual domain scores range:Physical health(0-32),Pain(0-12),Planning(0-12),Intimate relationship(0-8),Burden to others(0-12),Emotional health(0-24),Body image(0-20),Fatigue(0-16). Higher score indicates better HRQOL. Baseline value was latest pre-dose assessment with a non-missing value including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score by Visit [ Time Frame: Baseline (Day 1) and Weeks 8, 12, 26, 40, 52, 64, 72 and 104 ]
    The FACIT-Fatigue scale was a 13-item questionnaire completed by the participant, which provides a measure of fatigue/quality of life, with a 7-day recall period. The participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The higher score for the questions, the greater the fatigue. The total score was the sum of the responses from all questions (inverted for reversed items) multiplied by 13, then divided by the number of questions answered, ranging from 0 (worse fatigue) to 52 (no fatigue) where a higher score indicates an improvement in the participant's health status and decrease in the score indicates worse fatigue/quality of life. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as the post-dose visit value minus Baseline value.
  • Percentage of Participants With Improvement in FACIT-Fatigue Score Exceeding the Minimal Clinically Important Difference (MCID, Greater Than or Equal to [>=]4) [ Time Frame: Weeks 8, 12, 26, 40, 52, 64, 72 and 104 ]
    The FACIT-Fatigue scale was a 13-item questionnaire completed by the participant, which provides a measure of fatigue/quality of life, with a 7-day recall period. The participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions, the greater the fatigue. The total score was the sum of the responses (inverted for reversed items) multiplied by 13, then divided by the number of questions answered, ranging from 0 (worse fatigue) to 52 (no fatigue) where a higher score indicates an improvement in the participant's health status and decrease in the score indicates worse fatigue/quality of life. A participant was considered to had an improvement exceeding the minimal clinically important difference if they had >=4 points improvement in their FACIT-Fatigue Scale score from Baseline. Percentage of participants with improvement in FACIT-Fatigue scale score exceeding the MCID (>=4 points) were summarized.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2017)
  • Proportion of subjects with a state of clinical remission at Week 64 (Major) [ Time Frame: Week 64 ]
    State of clinical remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day. Serological activity score, i.e., anti-dsDNA positivity, and/or hypocomplementemia, is excluded from the Clinical SLEDAI-2K endpoint
  • Proportion of subjects with a state of disease control at Week 104 (Major) [ Time Frame: Week 104 ]
    State of disease control defined as SLEDAI-2K score <=2, achieved without the use of immunosuppressant and with corticosteroids at a prednisone equivalent dose of <=5 mg/day.
  • Proportion of subjects with a state of disease control at each visit [ Time Frame: Up to Week 104 ]
    State of disease control defined as SLEDAI-2K score <=2, achieved without the use of immunosuppressant and with corticosteroids at a prednisone equivalent dose of <=5 mg/day.
  • Proportion of subjects with a state of clinical remission at each visit [ Time Frame: Up to Week 104 ]
    State of clinical remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day.
  • Proportion of subjects with a state of complete remission sustained for at least 24 weeks [ Time Frame: Up to Week 104 ]
    State of complete remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day that should at least sustain for 24 weeks
  • Proportion of subjects with a state of clinical remission at Week 104 [ Time Frame: Week 104 ]
    State of clinical remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day.
  • Proportion of subjects with a state of complete remission at each visit [ Time Frame: Up to Week 104 ]
    State of complete remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day
  • Time to first severe flare (Measured by Modified SLE flare index) [ Time Frame: Up to Week 104 ]
    The SLE flare index is categorized as "mild/moderate" or "severe" flare.
  • Time to first flare (Measured by Modified SLE flare index) [ Time Frame: Up to Week 104 ]
    SLE flare indicates an increase in SLE disease activity. SLE flare index identifies whether a subject has experienced mild/moderate or severe flare
  • Time to disease control sustained Week 104 [ Time Frame: Week 104 ]
    Time to disease control sustained defined as SLEDAI-2K score <=2, achieved without the use of immunosuppressant and with corticosteroids at a prednisone equivalent dose of <=5 mg/day
  • Time to clinical remission sustained at Week 64 [ Time Frame: Week 64 ]
    Time to clinical remission sustained defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day.
  • Duration of disease control at each visit [ Time Frame: Up to Week 104 ]
    Duration of disease control defined as SLEDAI-2K score <=2, achieved without the use of immunosuppressant and with corticosteroids at a prednisone equivalent dose of <=5 mg/day
  • Duration of clinical remission [ Time Frame: Up to Week 104 ]
    Duration of clinical remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day.
  • Change from baseline in SLEDAI-2K score by visit [ Time Frame: Baseline and up to Week 104 ]
    The SLEDAI-2K is a clinical index for measuring SLE disease activity.
  • Proportion of subjects with SLEDAI-2K organ improvement at each visit [ Time Frame: Up to Week 104 ]
    The SLEDAI-2K is a clinical index for measuring SLE disease activity
  • Proportion of subjects with SLEDAI-2K organ worsening at each visit [ Time Frame: Up to Week 104 ]
    The SLEDAI-2K is a clinical index for measuring SLE disease activity
  • Change from Baseline in Physician Global Assessment (PGA) at each visit [ Time Frame: Baseline and up to Week 104 ]
    PGA is a physician-reported visual analogue scale that provides an overall measure of the subject's current disease activity.
  • Proportion of subjects with Systemic Lupus International Collaborating Clinics (SLICC) damage index worsening compared with baseline at Week 52 and Week 104 [ Time Frame: Baseline and up to Week 104 ]
    The SLICC-American College of Rheumatology (ACR) Damage Index measures irreversible changes occurring since the diagnosis of SLE.
  • Proportion of subjects that meet the Lupus Low Disease Activity State (LLDAS) response criteria by visit [ Time Frame: Up to Week 104 ]
    The LLDAS incorporates multiple measures of disease activity, such as :SLEDAI-2K <=4, with no activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity; no new features of lupus disease activity compared with the previous assessment; PGA (scale 0-3), <=1; current prednisolone (or equivalent) dose <=7.5 mg daily; well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents.
  • Proportion of subjects with Adverse events (AE), serious AEs (SAE) and AEs of special interest (AESIs) [ Time Frame: Up to Week 104 ]
    An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose may result in death, life-threatening, requires in-subject hospitalization or prolongation of hospitalization, results in persistent disability or incapacity, or causes to congenital anomaly or birth defect. AESIs included changes in laboratory parameters and immunogenicity (both anti-belimumab and anti-rituximab antibodies will be assessed).
  • Change from Baseline in Patient Global Assessment (PtGA) at each visit [ Time Frame: Baseline and up to Week 104 ]
    In PtGA subjects will be asked to rate the severity of their SLE between 0 (Very Well) and 10 (Very Poor) that best represents their current level of disease activity.
  • Change from Baseline in LupusQoL domain summary scores (8 domains) at each visit [ Time Frame: Baseline and up to Week 104 ]
    The LupusQoL is a valid SLE specific health related qualify of life (HRQOL) instrument with 34 questions across 8 domains. Questions are related to the subject experience in the prior 4 weeks, and a 5-point Likert response format is used, ranging from 0 (all of the time) to 4 (never). A LupusQoL summary score for each domain is reported on a 0 to 100 scale, with greater values indicating better HRQOL
  • Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score at each visit [ Time Frame: Baseline and up to Week 104 ]
    FACIT-Fatigue scale includes 13-fatigue related questions for subject rates fatigue during the previous 7 days, yielding an overall score 0 to 52, with lowest score representing worst fatigue.
  • Proportion of subjects with improvement in FACIT-Fatigue score exceeding the Minimal Clinically Important Difference (MCID, >=4) at each visit [ Time Frame: Up to Week 104 ]
    FACIT-Fatigue scale includes 13-fatigue related questions for subject rates fatigue during the previous 7 days, yielding an overall score 0 to 52, with lowest score representing worst fatigue.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination With Rituximab to Adult Subjects With Systemic Lupus Erythematosus (SLE) - BLISS-BELIEVE
Official Title  ICMJE A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 104-Week Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination With Rituximab to Adult Subjects With Systemic Lupus Erythematosus (SLE)
Brief Summary The purpose of this study is to assess whether co-administration of belimumab and a single cycle of rituximab will optimize treatment with belimumab, which will result in improvements of clinical status with a favorable safety profile, by comparing subjects randomized to belimumab plus rituximab versus belimumab plus rituximab-placebo. Approximately 292 subjects will be randomized in a 1:2:1 ratio to 1 of 3 treatment arms; belimumab plus rituximab-placebo (Arm A, control), belimumab plus rituximab (Arm B, combination), or belimumab plus standard therapy (Arm C, reference). Belimumab will be administered as subcutaneous (SC) and rituximab-placebo or rituximab will be administered by intravenous (IV) infusions. The total duration of the study is for 104 weeks.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Systemic Lupus Erythematosus
Intervention  ICMJE
  • Drug: Belimumab
    Belimumab will be administered as SC injection once weekly via autoinjector in thigh or abdomen
  • Drug: Rituximab
    Rituximab will be administered as IV infusion of 1000mg at Week 4 and Week 6
  • Drug: Rituximab-placebo
    Saline will be administered as IV infusions at Week 4 and Week 6
  • Drug: Standard therapy (Including Immunosuppressants)
    Standard therapy will contain stable SLE medications including immunosuppressant to be administered from baseline through Week 104.
  • Drug: Standard therapy (Excluding Immunosuppressants)
    Standard therapy excluding Immunosuppressant will contain anti-malarials, NSAIDs, and/or corticosteroids with prednisone dose equivalent to <= 5 mg/day will administered through Week 104.
  • Drug: Steroid Taper
    Steroid taper will include prednisone doses equivalent to =< 5 mg/day in all Arms through Week 104.
Study Arms  ICMJE
  • Placebo Comparator: Belimumab + Placebo
    Eligible subjects will receive Belimumab 200 milligrams (mg) to be administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Subjects will also receive rituximab-placebo to be administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Subjects will receive standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Subjects will not receive treatment after 52 weeks and will be in observation until Week 104.
    Interventions:
    • Drug: Belimumab
    • Drug: Rituximab-placebo
    • Drug: Standard therapy (Excluding Immunosuppressants)
    • Drug: Steroid Taper
  • Experimental: Belimumab + Rituximab
    Eligible subjects will receive Belimumab 200 mg to be administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Subjects will also receive rituximab 1000 mg to be administered by IV infusions at Weeks 4 and 6 in double blind manner. Subjects will receive standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Subjects will not receive treatment after 52 weeks and will be in observation until Week 104.
    Interventions:
    • Drug: Belimumab
    • Drug: Rituximab
    • Drug: Standard therapy (Excluding Immunosuppressants)
    • Drug: Steroid Taper
  • Belimumab + Standard therapy
    Eligible subjects will receive open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Subjects will also receive standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
    Interventions:
    • Drug: Belimumab
    • Drug: Standard therapy (Including Immunosuppressants)
    • Drug: Steroid Taper
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 7, 2020)
292
Original Estimated Enrollment  ICMJE
 (submitted: October 13, 2017)
200
Actual Study Completion Date  ICMJE July 7, 2021
Actual Primary Completion Date May 29, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects must be >=18 years of age at the time of signing the informed consent.
  • Subjects who have clinical diagnosis of SLE based on 4 or more of the 11 American College of Rheumatology (ACR) criteria.
  • Subjects who have a screening SLEDAI-2K score >=6 (This refers to the total score. Serological activity, i.e., anti-double stranded deoxyribonucleic acid [dsDNA]) positivity and/or hypocomplementemia is not required to be present in SLEDAI-2K assessment, but are scored if present).
  • Subjects who have unequivocally positive autoantibody test results defined as an anti-nuclear (ANA) titer >=1:80 and/or a positive anti-dsDNA (>=30 International Units per milliliter [IU/mL]) serum antibody test from 2 independent time points as follows: Positive test results from 2 independent time points within the study screening period. Screening results must be based on the study's central laboratory results. Or, one positive historical test result and 1 positive test result during the screening period.
  • Subjects who are on a stable SLE treatment regimen consisting of any of these medications (alone or in combination) for a period of at least 30 days prior to Day 1 (i.e. day of first dose of study treatment) with the exception that switching one agent for another of the same class for tolerability or availability reasons, which will be allowed within 30 days of Day 1: Corticosteroids (prednisone or prednisone equivalent); For those subjects on alternating daily doses of steroids, use the average of 2 daily doses to calculate the average daily steroid dose; Any immunosuppressant or immunomodulatory agents including methotrexate, azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil, mycophenolate mofetil hydrochloride, and mycophenolate sodium), calcineurin inhibitors (example [e.g.] tacrolimus, cyclosporine), sirolimus, oral cyclophosphamide, 6-mercaptopurine, mizoribine, or thalidomide; Anti-malarials (e.g., hydroxychloroquine, chloroquine, quinacrine); Non steroidal anti-inflammatory drugs (NSAIDs).
  • Male and/or female. A female subject is eligible to participate if she is not pregnant not breastfeeding, and at least one of the these conditions applies: Not a woman of childbearing potential (WOCBP) or A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 16 weeks after the last dose of belimumab, or at least 12 months after the last dose of rituximab or rituximab-placebo.
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

  • Symptomatic herpes zoster within 3 months prior to screening.
  • Evidence of active or latent tuberculosis (TB). Documentation may include medical history and examination, chest X-rays (posterior, anterior, and lateral), and TB testing: either a positive tuberculin skin test (TST; defined as a skin induration ≥5 mm at 48 to 72 hours, regardless of Baccillus Calmette-Guerin (BCG) or other vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold Plus test.
  • Significant allergies to humanized monoclonal antibodies.
  • History of hypersensitivity to belimumab and/or rituximab or known to have titers of human anti-mouse antibody or history of hypersensitivity reactions when treated with other diagnostic or therapeutic monoclonal antibodies.
  • Lymphoma, leukemia, or any malignancy within the past 5 years (yrs) except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 yrs.
  • Alanine transferase (ALT) greater than 2 times upper limit of normal (ULN).
  • Bilirubin greater than 1.5 times ULN (isolated bilirubin greater than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
  • Immunoglobulin A (IgA) deficiency (IgA level less than 10 milligram per deciliter [mg/dL]).
  • Immunoglobulin G (IgG) less than 250 mg/dL. For Germany only, IgG less than 400mg/dL.
  • Neutrophils less than 1.5 times 10^9.
  • Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
  • Severe heart failure (New York Heart Association Class IV) or other severe, uncontrolled cardiac disease.
  • QT interval corrected (QTc) greater than 450 millisecond (msec) or QTc greater than 480 msec in subjects with bundle branch block.
  • Subjects who have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
  • Subjects who have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, psychiatric, malignancy, or infectious diseases) which, in the opinion of the principal investigator, could confound the results of the study or put the subject at undue risk.
  • Subjects who have an acute or chronic infection requiring management as : Currently on any suppressive therapy for a chronic infection such as pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria); Hospitalization for treatment of infection within 60 days of Day 1; subjects who had infection requiring treatment with parenteral (IV or intramuscular [IM]) antibiotics (antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within 60 days of Day 1. Prophylactic anti-infective treatment is allowed.
  • Subjects who have severe lupus kidney disease (defined by proteinuria greater than 6 gram (g)/24 hours or equivalent using spot urine protein to creatinine ratio, or serum creatinine greater than 2.5 mg/dL), or have severe active nephritis requiring induction therapy not permitted by protocol (e.g., IV cyclophosphamide), or have required hemodialysis or high dose prednisone or equivalent (greater than 100 mg/day) within 90 days of Day 1.
  • Subjects who have severe 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 1.
  • Subjects who have a planned surgical procedure, laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the principal investigator, makes the subject unsuitable for the study.
  • Subjects who have evidence of serious suicide risk, including any history of suicidal behavior in the last 6 months and/or any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) in the last 2 months or who, in the investigator's opinion, pose a significant suicide risk.
  • Subjects who have a history of an anaphylaxis reaction to parenteral administration of contrast agents, human or murine proteins, or monoclonal antibodies.
  • Subjects who have received live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines during the screening period or during the study.
  • Subjects who have received any of the these prior/concomitant therapy within 364 days of Day 1: Belimumab; Rituximab; Abatacept; Any B cell targeted therapy (anti-cluster of differentiation-20 [CD] agents other than rituximab, anti CD22 [epratuzumab], anti-CD52 [alemtuzumab], BLyS-receptor fusion protein [BR3], Trans-membrane activator and calcium-modulator and cytophilin ligand interactor [TACI] Fc, anti B-cell activating factor [BAFF] (LY2127399), anti-Interferon alpha agents or anti-BLyS other than belimumab); A biologic investigational agent other than B cell targeted therapy (e.g., abetimus sodium, anti CD40L antibody [BG9588/ IDEC 1311]). (Investigational agent applies to any drug not approved for sale in the country in which it is being used).
  • Subjects who have required 3 or more courses of systemic corticosteroids within 364 days of Day 1. (Topical or inhaled steroids are permitted).
  • Subjects who have received any of these within 90 days of Day 1: Anti- Tumor Necrosis Factor (Anti-TNF) therapy (e.g., adalimumab, etanercept, infliximab); Interleukin-1 receptor antagonist (anakinra); Intravenous immunoglobulin (IVIG); High dose prednisone or equivalent (greater than 100 mg/day); Plasmapheresis.
  • Subjects who have received any of the these within 60 days of Day 1: A non-biologic investigational agent (Investigational agent applies to any drug not approved for sale in the country in which it is being used); IV cyclophosphamide and, for Germany only, oral cyclophosphamide; Any steroid injection (e.g., intramuscular [IM], intraarticular, or IV).
  • Positive immunodeficiency virus (HIV) antibody test.
  • Positive serology for Hepatitis B (HB), defined as HB surface antigen positive (HBsAg+) OR HB core antibody positive (HBcAb+).
  • Positive Hepatitis C (HCV) antibody test.
  • Subjects who have current drug or alcohol dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 1.
  • Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study.
  • Unable to administer study treatment (belimumab) by SC injection and has no other reliable resource to administer the injection.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Canada,   France,   Germany,   Korea, Republic of,   Mexico,   Netherlands,   Russian Federation,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03312907
Other Study ID Numbers  ICMJE 205646
2016-003050-32 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Current Responsible Party GlaxoSmithKline
Original Responsible Party Same as current
Current Study Sponsor  ICMJE GlaxoSmithKline
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date February 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP