A Long Term Extension Study of WA19926 (NCT01007435) of Tocilizumab (RoActemra/Actemra) in Participants With Early, Moderate to Severe Rheumatoid Arthritis (RA)
2019年2月11日 更新者：Hoffmann-La Roche
A Multicenter, Open-Label, Single Arm, Long Term Extension Study of WA19926 to Describe Safety During Treatment With Tocilizumab in Patients With Early, Moderate to Severe Rheumatoid Arthritis
This open-label, single arm, multicenter long-term extension study of WA19926 (NCT01007435) will evaluate the safety and efficacy of tocilizumab in participants with early, moderate to severe RA who have completed the 104-week WA19926 (NCT01007435) core study.
Eligible participants will be those who are expected to benefit from the study medicine based on the investigator's discretion.
調査の概要
研究の種類
介入
入学 (実際)
23
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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GO
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Goiania、GO、ブラジル、74110-120
- CIP - Centro Internacional de Pesquisa
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MG
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Juiz de Fora、MG、ブラジル、36036-330
- Centro Mineiro de Pesquisa - CMiP
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PR
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Curtiba、PR、ブラジル、80030-110
- Centro de Estudos em Terapias Inovadoras - CETI
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RS
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Porto Alegre、RS、ブラジル、90610-000
- Hospital Sao Lucas - PUCRS
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SP
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Sao Paulo、SP、ブラジル、04026-000
- Universidade Federal de Sao Paulo - UNIFESP; Reumatologia
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Sao Paulo、SP、ブラジル、04266-010
- Centro Paulista de Investigacao Clinica - CEPIC
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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
1年歳以上 (子、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:
- Participants who completed their last WA19926 (NCT01649804) core study visit (Week 104) and who may benefit from study drug treatment according to the Investigator's assessment
- No current or recent adverse event or laboratory finding preventing the use of tocilizumab 8 mg/kg at baseline visit
- Women of childbearing potential must agree to use highly reliable contraception during the treatment period
Exclusion Criteria:
- Pregnant or breastfeeding females
- Participants who have withdrawn prematurely from the WA19926 (NCT01649804) core study for any reason
- Treatment with any investigational agent or cell-depleting therapies since the last administration of study drug in WA19926 (NCT01649804)
- Treatment with an anti-tumor necrosis factor (TNF) or anti-interleukin (IL) 1 agent, or a T-cell costimulation modulator since the last administration of study drug in WA19926 (NCT01649804)
- Immunization with a live/attenuated vaccine since the last administration of study drug in WA19926 (NCT01649804)
- Diagnosis since last WA19926 (NCT01649804) visit (Week 104) of rheumatic autoimmune disease other than RA
- Diagnosis since last WA19926 (NCT01649804) visit (Week 104) of inflammatory joint disease other than RA
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, including tocilizumab and its excipients
- Evidence of severe uncontrolled concomitant disease or disorder
- Known active infections or history of recurrent infections
- Active tuberculosis requiring treatment in the previous 3 years
- History of alcohol, drug or chemical abuse since inclusion in the WA19926 (NCT01649804) study
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：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：Tocilizumab
Participants will receive tocilizumab 8 milligrams per kilogram (mg/kg) intravenously (IV) every 4 weeks for up to 104 weeks.
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Participants will receive tocilizumab 8 mg/kg IV every 4 weeks for up to 104 weeks.
他の名前：
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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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Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
時間枠：Baseline up to approximately 104 weeks
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An adverse event (AE) is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom or disease temporarily associated with use of study drug, regardless of its relation to study drug.
A TEAE is an AE that occurs only once treatment has started.
An SAE can be a) fatal, b) life-threatening, c) requires/prolongs hospitalization, d) results in persistent/significant incapacity/disability, e) results in congenital anomaly/birth defect or f) is considered as a significant medical event by the investigator.
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Baseline up to approximately 104 weeks
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Percentage of Participants With TEAEs of Special Interest
時間枠：Baseline up to approximately 104 weeks
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An AE is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom or disease temporarily associated with use of study drug, regardless of its relation to study drug.
A TEAE is an AE that occurs only once treatment has started.
Nine categories of AE of special interest are identified for tocilizumab which includes a) serious/medically significant infections, b) myocardial infarction/acute coronary syndrome, c) gastrointestinal perforations, d) malignancies, e) anaphylaxis/hypersensitivity reactions, f) demyelinating disorders, g) stroke, h) serious and/or medically significant bleeding events, and i) serious/medically significant hepatic events.
Data reported is an average of the nine categories.
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Baseline up to approximately 104 weeks
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Percentage of Participants With TEAEs Leading to Change in Dose or Study Drug Discontinuation
時間枠：Baseline up to approximately 104 weeks
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An AE is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom or disease temporarily associated with use of study drug, regardless of its relation to study drug.
A TEAE is an AE that occurs only once treatment has started.
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Baseline up to approximately 104 weeks
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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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Change From Baseline (CFB) in Disease Activity Score 28 Using Erythrocyte Sedimentation Rate (DAS28-ESR) at Specified Time Points
時間枠：Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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The DAS28-ESR is a combined index for measuring disease activity in rheumatoid arthritis (RA).
The index includes swollen joint counts (SJC) and tender joint counts (TJC), both scored 0-28 (higher scores indicate higher disease activity), as well as acute phase response (APR) determined as erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and general health (GH) (patient global assessment of disease activity [PGA] using visual analog scale [VAS], range 1-100 millimeters [mm]) (higher scores indicate higher disease activity).
DAS28-ESR is calculated according to the following formula: DAS28-ESR equals (=) [0.56 multiplied by (*) the square root (√) of TJC] plus (+) [0.28 * √ of SJC] + (0.70 * the natural logarithm [ln] ESR in mm/h) + (0.014*GH in mm VAS).
DAS28-ESR scale is transformed and ranges from 0 to 10.
A negative CFB indicated improvement.
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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CFB in Simplified Disease Activity Index (SDAI) Score at Specified Time Points
時間枠：Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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The SDAI is a combined index for measuring disease activity.
SDAI is the sum of TJC and SJC, both scored 0-28 (higher scores indicate higher disease activity), physician global assessment (PhGA) and PGA of disease activity, both scored 0 to 10 centimeters (cm) as assessed by VAS, and C-reactive protein level (CRP) in milligrams per deciliter (mg/dL) where normal is less than (<) 1 mg/dL.
SDAI is calculated according to the following formula: SDAI = TJC + SJC + PhGA + PGA + CRP.
SDAI ranges from 0 to 86.
A negative CFB indicated improvement.
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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CFB in Swollen Joint Count (SJC) at Specified Time Points
時間枠：Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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For SJC, a total of 66 joints are assessed.
The presence of a swollen joint is scored as 1 and absence as 0. Total score is calculated by adding the scores, which ranges from 0 (best possible score or no swollen joint) to 66 (worse possible score or all swollen joints).
Lower scores indicated no swollen joint and higher scores indicated worsening swollen joints.
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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CFB in Tender Joint Count (TJC) at Specified Time Points
時間枠：Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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The number of tender joints is recorded on the joint assessment form, no tenderness = 0, tenderness = 1, for 68 joints and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 68.
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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Percentage of Participants Reaching Clinical Remission (DAS28-ESR Score Less Than [<] 2.6 and/or SDAI Score Less Than or Equal to [</=] 3.3) Among Participants for Whom Tocilizumab Treatment Was Discontinued
時間枠：Baseline up to approximately 104 weeks
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Remission: DAS28-ESR score <2.6 and SDAI score </=3.3.
DAS28-ESR index included SJC and TJC, both scored 0-28, as well as APR determined as ESR in mm/hr, and GH (ranges 1-100 mm; higher scores=higher disease activity).
DAS28=(0.56*√TJC)+(0.28*√SJC)
+(0.70*ln
ESR) +(0.014*GH).
DAS28-ESR scale is transformed and ranges from 0 to 10. Negative CFB indicated improvement.
DAS28 >2.6 (clinical remission); DAS28 2.6 to 3.2 (low disease activity); DAS28 >3.2 to 5.1 = moderate to high disease activity.
SDAI is sum of TJC and SJC (both scored 0-28), PhGA and PGA of disease activity (both scored 0 to 10 cm as assessed by VAS, higher scores=higher disease activity), and CRP in mg/dL where normal is <1 mg/dL.
SDAI=TJC + SJC + PhGA + PGA + CRP.
SDAI ranged from 0 to 86.
A negative CFB indicated improvement.
SDAI <=3.3 (clinical remission), >3.4 to 11 (low disease activity) >11 to 26 (moderate disease activity), and >26 = (high/severe disease activity).
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Baseline up to approximately 104 weeks
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Time to RA Crisis Among Participants Who Discontinued After Clinical Remission
時間枠：Baseline up to approximately 104 weeks
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RA crisis is any worsening of participant disease acitivity that, in the opinion of the investigator, required intensified treatment other than supportive therapy, and may have included restart of the treatment with the study drug.
Time to RA crisis is defined as the period of remission without drug until the RA crisis documentation.
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Baseline up to approximately 104 weeks
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CFB in PGA of Disease Activity Using VAS Score at Specified Time Points
時間枠：Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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PGA of disease activity is assessed on a 0 to 100 mm horizontal VAS by the participant.
The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity).
A negative CFB indicated improvement.
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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CFB in PGA of Pain Using VAS Score at Specified Time Points
時間枠：Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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PGA of pain is assessed on a 0 to 100 mm horizontal VAS.
The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm, and is described as "unbearable pain".
A negative change indicated improvement.
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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CFB in PhGA of Disease Activity Using VAS Score at Specified Time Points
時間枠：Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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PhGA of disease activity is assessed on a 0 to 100 mm horizontal VAS by the physician.
The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as "maximum disease activity" (maximum arthritis disease activity).
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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CFB in Health Assessment Questionnaire-Disease Index (HAQ-DI) Score at Specified Time Points
時間枠：Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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HAQ-DI is a self-reported participant questionnaire specific for RA.
It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities.
Each domain has at least 2 component questions.
There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do.
Total score for HAQ-DI is the sum of all questions and ranges from 0 = without any difficulty to 60 = unable to do.
A negative CFB indicates improvement.
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Baseline, Weeks 12, 24, 36, 48, 56, 68, 80, 92, 104, early withdrawal (up to 104 weeks), follow-up 1 (8 weeks after the last visit or discontinuation; 112 weeks), follow-up 2 (16 weeks after the last visit or discontinuation; 120 weeks)
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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
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)
2013年12月9日
一次修了 (実際)
2016年5月11日
研究の完了 (実際)
2016年5月11日
試験登録日
最初に提出
2012年8月16日
QC基準を満たした最初の提出物
2012年8月16日
最初の投稿 (見積もり)
2012年8月20日
学習記録の更新
投稿された最後の更新 (実際)
2019年5月13日
QC基準を満たした最後の更新が送信されました
2019年2月11日
最終確認日
2019年2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。