A Long Term Extension Study of WA19926 (NCT01007435) of Tocilizumab (RoActemra/Actemra) in Participants With Early, Moderate to Severe Rheumatoid Arthritis (RA)
2019년 2월 11일 업데이트: 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.
연구 개요
연구 유형
중재적
등록 (실제)
23
단계
- 3단계
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연구 장소
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GO
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Goiania, GO, 브라질, 74110-120
- CIP - Centro Internacional de Pesquisa
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MG
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Juiz de Fora, MG, 브라질, 36036-330
- Centro Mineiro de Pesquisa - CMiP
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PR
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Curtiba, PR, 브라질, 80030-110
- Centro de Estudos em Terapias Inovadoras - CETI
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RS
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Porto Alegre, RS, 브라질, 90610-000
- Hospital Sao Lucas - PUCRS
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SP
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Sao Paulo, SP, 브라질, 04026-000
- Universidade Federal de Sao Paulo - UNIFESP; Reumatologia
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Sao Paulo, SP, 브라질, 04266-010
- Centro Paulista de Investigacao Clinica - CEPIC
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
1년 이상 (어린이, 성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 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.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
기간: 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
기간: 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
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Change From Baseline (CFB) in Disease Activity Score 28 Using Erythrocyte Sedimentation Rate (DAS28-ESR) at Specified Time Points
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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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연구 주요 날짜
연구 시작 (실제)
2013년 12월 9일
기본 완료 (실제)
2016년 5월 11일
연구 완료 (실제)
2016년 5월 11일
연구 등록 날짜
최초 제출
2012년 8월 16일
QC 기준을 충족하는 최초 제출
2012년 8월 16일
처음 게시됨 (추정)
2012년 8월 20일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2019년 5월 13일
QC 기준을 충족하는 마지막 업데이트 제출
2019년 2월 11일
마지막으로 확인됨
2019년 2월 1일
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