A Study of Tocilizumab Added to DMARDs in Patients With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to DMARDs.
28. februar 2018 opdateret af: Hoffmann-La Roche
Local Open-label Multicenter Study to Evaluate the Quality of Life in Patients With Moderate to Severe Active Rheumatoid Arthritis and an Inadequate Response to DMARDs When Adding Tocilizumab (TCZ)
This open-label single arm study will evaluate the efficacy and safety of tocilizumab added to traditional disease-modifying antirheumatic drugs (DMARDs) in patients with moderate to severe active rheumatoid arthritis and an inadequate response to DMARDs.
Patients will receive tocilizumab 8 mg/kg by intravenous infusion every 4 weeks for 24 weeks, in addition to their current non-biologic DMARDs at stable doses.
Anticipated time on study treatment is 24 weeks, and the target sample size is 200.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
201
Fase
- Fase 4
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Chelyabinsk, Den Russiske Føderation, 454076
- Chelyabinsk Regional Clinical Hospital; Rheumatology
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Cherkess, Den Russiske Føderation, 369000
- Republican clinical hospital of Karachai-Cherkess; Rheumatologic Department
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Ekaterinburg, Den Russiske Føderation, 620102
- Municipal Autonomous Institution of Healthcare "City Clinical Hospital #40"
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Ekaterinburg, Den Russiske Føderation, 620102
- Sverdlovsk Regional Clinical Hospital # 1; Rheumatology Dept
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Irkutsk, Den Russiske Føderation, 664047
- Irkutsk Regional Consulting and Diagnostic Clinical Center; Regional Center of Reumatolodic Deasise
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Izhevsk, Den Russiske Føderation, 426009
- Republican Clinicodiagnostic Center
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Kaliningrad, Den Russiske Føderation, 236016
- Kaliningrad Regional Clinical Hospital; Rheumatologic Department
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Kemerovo, Den Russiske Føderation, 650099
- War Veterans Regional Clinical Hospital;Therapy Department
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Kirov, Den Russiske Føderation, 610028
- Kirov Regional Clinical Hospital; Reumatology Department
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Krasnodar, Den Russiske Føderation, 350086
- GUZ Regional clinical hospital # 1
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Kursk, Den Russiske Føderation, 305007
- GMU Kursk regional clinical hospital
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Moscow, Den Russiske Føderation, 123060
- Head Clinical Hospital of Internal Affair Ministry of Russia
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Moscow, Den Russiske Føderation, 129110
- Vladimirskiy Regional Scientific Research Inst.
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Moscow, Den Russiske Føderation, 115522
- FSBI "Scientific Research Institute of Rheumatology" of russian Academy of Medical Sciences
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Moscow, Den Russiske Føderation, 115682
- FSBI "FSCC of particularized sorts of medical care and medical technologies of FMBA"
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Moscow, Den Russiske Føderation, 121359
- FGU Central Clinical Hospital with Polyclinic Administration President RF
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Nizhny Novgorod, Den Russiske Føderation, 603126
- SIH Nizhny Novgorod Regional Clinical Hospital n.a. Semashko
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Petrozavodsk, Den Russiske Føderation, 185019
- Republican Hospital named after V.A. Baranov
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Rostov-na-Donu, Den Russiske Føderation, 344022
- Rostov State Medical University; Cardiorheumatology Department
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Smolensk, Den Russiske Føderation, 214001
- Clinical hospital #1
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Surgut, Den Russiske Føderation, 628408
- Surgut Region Clinical Hospital
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Tjumen, Den Russiske Føderation, 625023
- Glpu Tjumen Regional Clinical Hospital #1
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UFA, Den Russiske Føderation, 450005
- Republican clinical hospital named after G.G. Kuvatov
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Ulyanovsk, Den Russiske Føderation, 432063
- State Institution of Healthcare Ulyanovsk Regional Clinical Hospital
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Veliky Novgorod, Den Russiske Føderation, 173008
- GUZ "Novgorod Regional Clinical Hospital"; Cardioreumatological
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Voronezh, Den Russiske Føderation, 394066
- Voronezh Regional Clinical Hospital #1
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Voronezh, Den Russiske Føderation, 394066
- Budget Institution of Healthcare of Voronezh Region "Voronezh Regional Clinical Hospital #1"
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Yaroslavl, Den Russiske Føderation, 150062
- SHI Yaroslavl Regional Clinical Hospital
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- adult patients, >/= 18 years of age
- moderate to severe active rheumatoid arthritis of >/=6 months duration
- inadequate clinical response to current non-biologic DMARDs
- current DMARDs must be at stable dose for 8 weeks prior to study entry
- oral corticosteroids (</=10mg/day prednisone or equivalent) and NSAIDs must be at stable dose for >/=4 weeks prior to screening
Exclusion Criteria:
- rheumatic autoimmune disease other than RA
- history of or current inflammatory joint disease other than RA
- previous treatment with any biologic DMARD
- functional class IV as defined by the ACR classification
- intra-articular or parenteral corticosteroids within 6 weeks prior to screening
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: 1
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8 mg/kg iv every 4 weeks for 24 weeks
stable doses at investigator's prescription
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Health Assessment Questionnaire (HAQ) Score
Tidsramme: Weeks 0, 4, 8, 12, 16, 20, and 24 and Withdrawal Visit
|
HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity.
To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen.
Scoring was as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all.
Minimum score was 0, maximum score was 3. Withdrawal Visit is the final visit prior to the withdrawal of the subject from the study.
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Weeks 0, 4, 8, 12, 16, 20, and 24 and Withdrawal Visit
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Percentage of Participants With an HAQ Score Decrease of 20 Percent (%), 50%, and 70% During Tocilizumab Treatment
Tidsramme: Weeks 4, 8, 12, 16, 20, and 24
|
HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity.
To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen.
Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all.
Minimum score was 0, maximum score was 3.
|
Weeks 4, 8, 12, 16, 20, and 24
|
|
Change in HAQ Score at Week 24
Tidsramme: Baseline and Week 24
|
HAQ includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity.
To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen.
Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all.
Minimum score was 0, maximum score was 3.
|
Baseline and Week 24
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Pain Score as Assessed by Visual Analogue Scale (VAS)
Tidsramme: Weeks 0, 4, 8, 12, 16, 20, and 24
|
Participant's global assessment of pain was assessed using a 100-millimeter (mm) horizontal VAS (0 to 100 mm) with 0=pain absent and 100=intolerable pain.
Participants responded by placing a mark on the line to indicate their current level of pain.
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Weeks 0, 4, 8, 12, 16, 20, and 24
|
|
European Quality of Life - 5 Dimensions (EQ-5D) Score
Tidsramme: Weeks 0, 4, 8, 12, 16, 20, and 24
|
EQ-5D questionnaire assess 5 domains of quality of life including mobility, self-care, habitual daily activities, pain, discomfort, and anxiety/depression.
Each of five domains was assessed by 3 levels depending on severity of a problem and scored using the following: 1=no disturbances, 2=moderate disturbances, 3=severe disturbances.
Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
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Weeks 0, 4, 8, 12, 16, 20, and 24
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Change in EQ-5D Score at Week 24 From Baseline
Tidsramme: Baseline and Week 24
|
EQ-5D questionnaire assess 5 domains of quality of life including mobility, self-care, habitual daily activities, pain, discomfort, and anxiety/depression.
Each of five domains was assessed by 3 levels depending on severity of a problem and scored using the following: 1=no disturbances, 2=moderate disturbances, 3=severe disturbances.
Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Minimum clinically significant change in EQ-5D corresponds to the parameter differences before and after treatment = 0.10.
Graduations of assessment of the therapy efficacy by EQ-5D are: Difference (Δ) EQ-5D less than (<)0.10 points: none; 0.10 less than or equal to (≤)Δ EQ-5D ≤0.24: minimal effect; 0.24≤ Δ EQ-5D <0.31: satisfactory effect; Δ EQ-5D greater than or equal to (≥)0.31 points: pronounced effect.
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Baseline and Week 24
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General Health Score as Assessed by EQ-5D VAS
Tidsramme: Weeks 0, 4, 8, 12, 16, 20, and 24
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Participant-reported general health quality was assessed using an EQ-5D 100-mm horizontal VAS (0 to 100 mm) with 0=worst health state and 100=the best health state.
The participants were asked to mark the line that corresponded to assessment of general health quality.
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Weeks 0, 4, 8, 12, 16, 20, and 24
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Percentage of Participants Achieving a Positive Response on Health Quality Assessment of EQ-5D
Tidsramme: Weeks 0, 4, 8, 12, 16, 20, and 24
|
Participant-reported general health quality was assessed using an EQ-5D 100-mm horizontal VAS (0 to 100 mm) with 0=worst health state and 100=the best health state.
The participants were asked to mark the line that corresponded to assessment of general health quality.
Positive response was defined as an increase of EQ-5D score by 0.1 or more i.e. it is a clinically significant increase.
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Weeks 0, 4, 8, 12, 16, 20, and 24
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Change in General Health Assessed by VAS
Tidsramme: Baseline and Week 24
|
Participant-reported general health quality was assessed using an EQ-5D 100-mm horizontal VAS (0 to 100 mm) with 0=worst health state and 100=the best health state.
The participants were asked to mark the line that corresponded to assessment of general health quality.
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Baseline and Week 24
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Disease Activity Score Based on 28-Joint Count (DAS28)
Tidsramme: Weeks 0, 4, 8, 12, 16, 20, and 24
|
DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity.
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Weeks 0, 4, 8, 12, 16, 20, and 24
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Change in DAS28 Score From Baseline to Week 24
Tidsramme: Baseline and Week 24
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Baseline and Week 24
|
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Percentage of Patients With Varied Disease Activity Assessed Using DAS28 During Tocilizumab Treatment
Tidsramme: Weeks 0, 4, 8, 12, 16, 20, and 24
|
DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR mm/hour, and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity.
Disease activity: 0=remission (DAS28 less than [<] 2.6), I=low (DAS28 less than or equal to [≤]2.6 to <3.2), II=moderate (DAS28=3.2
to 5.1), III=high (DAS28 greater than [>]5.1).
|
Weeks 0, 4, 8, 12, 16, 20, and 24
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Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
Tidsramme: Weeks 0, 4, 8, 12, 16, 20, and 24
|
ACR20/50/70 response: ≥20%, ≥50%, or ≥70% improvement, respectively, in swollen/tender joint count (66 joints assessed for swelling and 68 joints assessed for tenderness) and in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and acute phase response: C-reactive protein (CRP) or ESR.
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Weeks 0, 4, 8, 12, 16, 20, and 24
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Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
Tidsramme: Weeks 4, 8, 12, 16, 20, and 24
|
The DAS28-based EULAR response criteria were used to measure individual response as no effect, good effect, and moderate effect, depending on the extent of change from baseline and the level of disease activity reached.
Good effect: change from baseline >1.2 with DAS28 score ≤3.2; moderate effect: change from baseline >1.2 with DAS28 score 3.2 to 5.1 or change from baseline >0.6 to <1.2 with DAS28 score <3.2; no effect: change from baseline ≤0.6 or change from baseline >0.6 and ≤1.2 with DAS28 score >5.1.
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Weeks 4, 8, 12, 16, 20, and 24
|
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C-Reactive Protein
Tidsramme: Weeks 4, 8, 12, 16, 20, and 24
|
CRP (milligrams/Liter) is a mediator of inflammation, acute phase protein.
|
Weeks 4, 8, 12, 16, 20, and 24
|
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Erythrocyte Sedimentation Rate
Tidsramme: Weeks 4, 8, 12, 16, 20, and 24
|
ESR (mm/hr) is used to determine the acute phase response.
|
Weeks 4, 8, 12, 16, 20, and 24
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
31. oktober 2009
Primær færdiggørelse (Faktiske)
14. februar 2011
Studieafslutning (Faktiske)
14. februar 2011
Datoer for studieregistrering
Først indsendt
15. oktober 2009
Først indsendt, der opfyldte QC-kriterier
15. oktober 2009
Først opslået (Skøn)
16. oktober 2009
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
29. marts 2018
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
28. februar 2018
Sidst verificeret
1. februar 2018
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- ML22665
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .