GSK1550188 A 52 Week Study of Belimumab Versus Placebo in the Treatment of Subjects With Systemic Lupus Erythematosus (SLE) Located in Northeast Asia
2019年9月20日 更新者：GlaxoSmithKline
The purpose of this study is to evaluate the efficacy and safety of belimumab in addition to standard therapy compared to placebo in subjects in Northeast Asia with systemic lupus erythematosus (SLE) over a 52 week period.
調査の概要
詳細な説明
The purpose of this study is to demonstrate the efficacy and safety of belimumab 10mg/kg administered intravenously (IV) every 4 weeks compared to placebo, in patients with SLE when added to standard of care therapy, as measured by the SLE Responder Index (SRI) at 52 weeks, defined by a composite endpoint using SELENA SLEDAI score, Physician's Global Assessment (PGA) and BILAG A and B organ domain scores.
研究の種類
介入
入学 (実際)
709
段階
- フェーズ 3
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Beijing、中国、100044
- GSK Investigational Site
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Beijing、中国、100029
- GSK Investigational Site
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Beijing、中国、100032
- GSK Investigational Site
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Chongqing、中国、400038
- GSK Investigational Site
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Shanghai、中国、200025
- GSK Investigational Site
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Shanghai、中国、200433
- GSK Investigational Site
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Shanghai、中国、200001
- GSK Investigational Site
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Shanghai、中国、200003
- GSK Investigational Site
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Tianjin、中国、300052
- GSK Investigational Site
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Anhui
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Hefei、Anhui、中国、230001
- GSK Investigational Site
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Guangdong
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Guangzhou、Guangdong、中国、510080
- GSK Investigational Site
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Guangzhou、Guangdong、中国、510630
- GSK Investigational Site
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Guangzhou、Guangdong、中国、510260
- GSK Investigational Site
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Heilongjiang
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Harbin、Heilongjiang、中国、150001
- GSK Investigational Site
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Hunan
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Changsha、Hunan、中国、410011
- GSK Investigational Site
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Changsha、Hunan、中国、410008
- GSK Investigational Site
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Jiangsu
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Nanjing、Jiangsu、中国、210029
- GSK Investigational Site
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Suzhou、Jiangsu、中国、215006
- GSK Investigational Site
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Shaanxi
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Xian、Shaanxi、中国、710032
- GSK Investigational Site
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Shandong
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Jinan、Shandong、中国、250012
- GSK Investigational Site
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Sichuan
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Chengdu、Sichuan、中国、610041
- GSK Investigational Site
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Yunnan
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Kunming、Yunnan、中国、650101
- GSK Investigational Site
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Zhejiang
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Hangzhou、Zhejiang、中国、310009
- GSK Investigational Site
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Busan、大韓民国
- GSK Investigational Site
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Daegu、大韓民国、700-721
- GSK Investigational Site
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Incheon、大韓民国、400-711
- GSK Investigational Site
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Seoul、大韓民国、137-701
- GSK Investigational Site
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Seoul、大韓民国、110-744
- GSK Investigational Site
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Seoul、大韓民国
- GSK Investigational Site
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Seoul、大韓民国、133-792
- GSK Investigational Site
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Suwon, Kyonggi-do、大韓民国、443-721
- GSK Investigational Site
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Chiba、日本、275-8580
- GSK Investigational Site
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Ehime、日本、791-0295
- GSK Investigational Site
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Fukuoka、日本、807-8555
- GSK Investigational Site
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Fukuoka、日本、810-8563
- GSK Investigational Site
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Hiroshima、日本、730-8619
- GSK Investigational Site
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Hiroshima、日本、739-0002
- GSK Investigational Site
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Hokkaido、日本、060-8648
- GSK Investigational Site
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Hokkaido、日本、060-8604
- GSK Investigational Site
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Hyogo、日本、675-8545
- GSK Investigational Site
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Miyagi、日本、980-8574
- GSK Investigational Site
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Nagasaki、日本、852-8501
- GSK Investigational Site
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Nagasaki、日本、857-1195
- GSK Investigational Site
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Okayama、日本、710-0824
- GSK Investigational Site
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Okinawa、日本、901-0243
- GSK Investigational Site
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Tochigi、日本、321-0293
- GSK Investigational Site
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Tokyo、日本、113-8431
- GSK Investigational Site
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- Age 18 years and older.
- Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) classification criteria.
- Have active SLE disease.
- Have positive anti-nuclear antibody (ANA) test results.
- Are on a stable SLE treatment regimen.
- Females of childbearing age are willing to use appropriate contraception
Exclusion Criteria:
- Have received treatment with any B cell targeted therapy at any time.
- Have received a biologic investigational agent in the past year.
- Have received 3 or more courses of systemic corticosteroids in the past year.
- Have received intravenous (IV) cyclophosphamide within 180 days prior to Day 0.
- Have severe lupus kidney disease.
- Have active central nervous system (CNS) lupus.
- Have had a major organ transplant.
- Have significant unstable or uncontrolled acute or chronic diseases or conditions not due to SLE.
- Have a planned surgical procedure.
- Cancer within the last 5 years, except for adequately treated skin cancer, or carcinoma in situ of the uterine cervix.
- Have required management of acute or chronic infections in the past 60 days.
- Have current drug or alcohol abuse or dependence.
- Have a historically positive test, or test positive at screening for HIV, Hepatitis B, or Hepatitis C.
- Have an IgA deficiency.
- Have severe laboratory Abnormalities.
- Have had anaphylactic reaction to X-ray contrast agents or biologic agents.
- Suicidal behavior or ideation.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
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プラセボコンパレーター：プラセボ
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Administered intravenously.
Dosing at Weeks 0, 2, and 4, and then every 4 weeks through Week 48, with a final evaluation at Week 52.
All study subjects will receive standard SLE therapies during the study.
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実験的：ベリムマブ
10mg/kg
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10mg/kg administered intravenously.
Dosing at Weeks 0, 2, and 4, then every 4 weeks through Week 48, with a final evaluation at Week 52.
All study subjects will receive standard SLE therapies during the study.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Percent of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response Rate at Week 52 for Double-blind Phase.
時間枠：Week 52
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SRI response is a composite index, defined as the percent of participants with >=4 point reduction from Baseline in safety of estrogen in lupus national assessment (SELENA) systemic lupus erythematosus disease activity index (SLEDAI) score and no worsening (increase of < 0.30 points from Baseline) in physicians global assessment (PGA) and no new British isles lupus assessment group (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with Baseline at the time of assessment (at Week 52 of the blinded period).
A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus.
PGA ranges from 0 (no activity) to 3 (severe activity).
BILAG has no range.
The higher thresholds of SELENA SLEDAI improvement (i.e., SRI5, SRI6, and SRI7) indicates a higher response (SRI5 is a 5 point SELENA SLEDAI reduction, SRI6 is a 6 point reduction, and SRI7 is a 7 point reduction).
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Week 52
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Percent of Participants With >=4 Point Reduction From Baseline in SELENA SLEDAI Score at Week 52 for Double-blind Phase.
時間枠：Baseline (Day 0) and Week 52
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The SELENA SLEDAI score is a weighted index for assessing SLE disease activity in which signs and symptoms, laboratory tests and physician's assessment for each of 9 organ system were given a weighted score and summed if present at the time of the visit or in the preceding 10 days.
A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus.
A decrease of 4 points or more equates to a clinically meaningful improvement.
The Baseline value of a variable is defined as the value of the variable measured at Day 0 prior to dosing.
In case of multiple results on Day 0 prior to dosing, the latest result was used.
If a Day 0 value was not available, the last available value prior to Day 0 was used.
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Baseline (Day 0) and Week 52
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Percent of Participants With SRI7 Response at Week 52 for Double-blind Phase.
時間枠：Baseline (Day 0) and Week 52
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SRI7 response is defined as the percent of participants with >=7 point reduction from Baseline in SELENA SLEDAI score and no worsening (increase of < 0.30 points from Baseline) in PGA and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with Baseline at the time of assessment (at Week 52 of the blinded period).
A SELENA SLEDAI score of 0 would suggest no lupus activity; while a score of 105 is the maximum calculable if all items were scored as being present from active lupus.
PGA ranges from 0 (no activity) to 3 (severe activity).
BILAG has no range.
The higher thresholds of SELENA SLEDAI improvement (i.e., SRI5, SRI6, and SRI7) indicates a higher response (SRI5 is a 5 point SELENA SLEDAI reduction, SRI6 is a 6 point reduction, and SRI7 is a 7 point reduction).
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Baseline (Day 0) and Week 52
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Number of Days of Daily Prednisone Dose <=7.5 mg/Day and/or Reduced by 50 Percent From Baseline Over 52 Weeks for Double-blind Phase.
時間枠：Week 52
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Number of days of daily prednisone dose <=7.5 mg/day and/or reduced by 50 percent over time through each scheduled visit during the blinded period were compared between belimumab and placebo using Rank ANCOVA model which was used for comparing belimumab and placebo.
The independent variables in the model included treatment group, Baseline prednisone dose level, country, Baseline SELENA SLEDAI score (<=9 vs. >=10) and complement levels (low C3 and/or C4 vs. no low C3 or C4).
This analysis was perfomed on the participants who used prednisone >7.5 mg/day at Baseline.
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Week 52
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Time to First Severe SLE Flare Index (SFI) Flare Over 52 Weeks for Double-blind Phase.
時間枠：52 weeks
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Time to first severe SLE flare is defined as the number of days from first treatment until the participant had an event (event date-treatement start date +1).
If a participant had a severe SFI flare and received protocol restricted medication then the event date was the earliest of the first severe SFI flare date, and the treatment failure date.
Analysis of severe SFI flare was performed on the modified SELENA SLEDAI SLE flare index in which the modification excluded severe flares that were triggered only by an increase in SELENA SLEDAI score to >12.
Analysis was from Cox proportional hazards model for the comparison between belimumab and placebo adjusting for country, Baseline SELENA SLEDAI score (<=9 vs. >=10) and complement levels (low C3 and/or C4 vs. no low C3 or C4).
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52 weeks
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Percent of Participants Achieving SLE SRI Response Rate for Open-label (OL) Phase
時間枠：Weeks 24 and 48 for Years 2, 3, 4, 5 and 6
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SRI response is a composite index, defined as the percent of participants with >=4 point reduction from Baseline in SELENA SLEDAI score and no worsening (increase of < 0.30 points from Baseline) in PGA and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with Baseline at time of assessment.
Excludes participants with a SELENA SLEDAI score <4 at baseline.
Participants randomized to belimumab in double-blinded (DB) phase, Baseline is last available value before first belimumab dose received in DB phase.
Participants randomized to placebo in DB phase, Baseline is last available value before receiving first belimumab dose in OL phase.
Observed case data are presented.Year 6 Week 48 is the Exit Visit obtained by slotting the Exit Visit to Week 48.
A SELENA SLEDAI score of 0 (no lupus activity) and a score of 105 (maximum).
PGA ranges from 0 (no activity) to 3 (severe activity).
BILAG has no range.
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Weeks 24 and 48 for Years 2, 3, 4, 5 and 6
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
- Gupta SV, Fanget MC, MacLauchlin C, Clausen VA, Li J, Cloutier D, Shen L, Robbie GJ, Mogalian E. Clinical and Preclinical Single-Dose Pharmacokinetics of VIR-2218, an RNAi Therapeutic Targeting HBV Infection. Drugs R D. 2021 Dec;21(4):455-465. doi: 10.1007/s40268-021-00369-w. Epub 2021 Nov 6.
- Zhou X, Lee TI, Zhu M, Ma P. Prediction of Belimumab Pharmacokinetics in Chinese Pediatric Patients with Systemic Lupus Erythematosus. Drugs R D. 2021 Dec;21(4):407-417. doi: 10.1007/s40268-021-00363-2. Epub 2021 Oct 9.
- Brunner HI, Abud-Mendoza C, Mori M, Pilkington CA, Syed R, Takei S, Viola DO, Furie RA, Navarra S, Zhang F, Bass DL, Eriksson G, Hammer AE, Ji BN, Okily M, Roth DA, Quasny H, Ruperto N. Efficacy and safety of belimumab in paediatric and adult patients with systemic lupus erythematosus: an across-study comparison. RMD Open. 2021 Sep;7(3):e001747. doi: 10.1136/rmdopen-2021-001747.
- Zhang F, Bae SC, Bass D, Chu M, Egginton S, Gordon D, Roth DA, Zheng J, Tanaka Y. A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea. Ann Rheum Dis. 2018 Mar;77(3):355-363. doi: 10.1136/annrheumdis-2017-211631. Epub 2018 Jan 2.
- Zhang F, Zheng J, Li Y, Wang G, Wang M, Su Y, Gu J, Li X, Bass D, Chu M, Curtis P, DeRose K, Kurrasch R, Lowe J, Meizlik P, Roth DA. Phase 3, long-term, open-label extension period of safety and efficacy of belimumab in patients with systemic lupus erythematosus in China, for up to 6 years. RMD Open. 2022 Apr;8(1):e001669. doi: 10.1136/rmdopen-2021-001669.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2011年5月23日
一次修了 (実際)
2015年9月15日
研究の完了 (実際)
2018年9月21日
試験登録日
最初に提出
2011年4月28日
QC基準を満たした最初の提出物
2011年4月28日
最初の投稿 (見積もり)
2011年5月2日
学習記録の更新
投稿された最後の更新 (実際)
2019年10月4日
QC基準を満たした最後の更新が送信されました
2019年9月20日
最終確認日
2019年9月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。