A Study of Tocilizumab Added to DMARDs in Patients With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to DMARDs.
keskiviikko 28. helmikuuta 2018 päivittänyt: 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.
Tutkimuksen yleiskatsaus
Tila
Valmis
Ehdot
Opintotyyppi
Interventio
Ilmoittautuminen (Todellinen)
201
Vaihe
- Vaihe 4
Yhteystiedot ja paikat
Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.
Opiskelupaikat
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Chelyabinsk, Venäjän federaatio, 454076
- Chelyabinsk Regional Clinical Hospital; Rheumatology
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Cherkess, Venäjän federaatio, 369000
- Republican clinical hospital of Karachai-Cherkess; Rheumatologic Department
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Ekaterinburg, Venäjän federaatio, 620102
- Municipal Autonomous Institution of Healthcare "City Clinical Hospital #40"
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Ekaterinburg, Venäjän federaatio, 620102
- Sverdlovsk Regional Clinical Hospital # 1; Rheumatology Dept
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Irkutsk, Venäjän federaatio, 664047
- Irkutsk Regional Consulting and Diagnostic Clinical Center; Regional Center of Reumatolodic Deasise
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Izhevsk, Venäjän federaatio, 426009
- Republican Clinicodiagnostic Center
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Kaliningrad, Venäjän federaatio, 236016
- Kaliningrad Regional Clinical Hospital; Rheumatologic Department
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Kemerovo, Venäjän federaatio, 650099
- War Veterans Regional Clinical Hospital;Therapy Department
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Kirov, Venäjän federaatio, 610028
- Kirov Regional Clinical Hospital; Reumatology Department
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Krasnodar, Venäjän federaatio, 350086
- GUZ Regional clinical hospital # 1
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Kursk, Venäjän federaatio, 305007
- GMU Kursk regional clinical hospital
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Moscow, Venäjän federaatio, 123060
- Head Clinical Hospital of Internal Affair Ministry of Russia
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Moscow, Venäjän federaatio, 129110
- Vladimirskiy Regional Scientific Research Inst.
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Moscow, Venäjän federaatio, 115522
- FSBI "Scientific Research Institute of Rheumatology" of russian Academy of Medical Sciences
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Moscow, Venäjän federaatio, 115682
- FSBI "FSCC of particularized sorts of medical care and medical technologies of FMBA"
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Moscow, Venäjän federaatio, 121359
- FGU Central Clinical Hospital with Polyclinic Administration President RF
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Nizhny Novgorod, Venäjän federaatio, 603126
- SIH Nizhny Novgorod Regional Clinical Hospital n.a. Semashko
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Petrozavodsk, Venäjän federaatio, 185019
- Republican Hospital Named After V.A. Baranov
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Rostov-na-Donu, Venäjän federaatio, 344022
- Rostov State Medical University; Cardiorheumatology Department
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Smolensk, Venäjän federaatio, 214001
- Clinical hospital #1
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Surgut, Venäjän federaatio, 628408
- Surgut Region Clinical Hospital
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Tjumen, Venäjän federaatio, 625023
- Glpu Tjumen Regional Clinical Hospital #1
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UFA, Venäjän federaatio, 450005
- Republican clinical hospital named after G.G. Kuvatov
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Ulyanovsk, Venäjän federaatio, 432063
- State Institution of Healthcare Ulyanovsk Regional Clinical Hospital
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Veliky Novgorod, Venäjän federaatio, 173008
- GUZ "Novgorod Regional Clinical Hospital"; Cardioreumatological
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Voronezh, Venäjän federaatio, 394066
- Voronezh Regional Clinical Hospital #1
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Voronezh, Venäjän federaatio, 394066
- Budget Institution of Healthcare of Voronezh Region "Voronezh Regional Clinical Hospital #1"
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Yaroslavl, Venäjän federaatio, 150062
- SHI Yaroslavl Regional Clinical Hospital
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Osallistumiskriteerit
Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.
Kelpoisuusvaatimukset
Opintokelpoiset iät
18 vuotta ja vanhemmat (Aikuinen, Vanhempi Aikuinen)
Hyväksyy terveitä vapaaehtoisia
Ei
Sukupuolet, jotka voivat opiskella
Kaikki
Kuvaus
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
Opintosuunnitelma
Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Ei satunnaistettu
- Inventiomalli: Yksittäinen ryhmätehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
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Kokeellinen: 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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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Health Assessment Questionnaire (HAQ) Score
Aikaikkuna: Weeks 0, 4, 8, 12, 16, 20, and 24 and Withdrawal Visit
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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
Aikaikkuna: 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.
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Weeks 4, 8, 12, 16, 20, and 24
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Change in HAQ Score at Week 24
Aikaikkuna: 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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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Pain Score as Assessed by Visual Analogue Scale (VAS)
Aikaikkuna: Weeks 0, 4, 8, 12, 16, 20, and 24
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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
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European Quality of Life - 5 Dimensions (EQ-5D) Score
Aikaikkuna: Weeks 0, 4, 8, 12, 16, 20, and 24
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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
Aikaikkuna: Baseline and Week 24
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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
Aikaikkuna: 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
Aikaikkuna: 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.
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
Aikaikkuna: Baseline and Week 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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Baseline and Week 24
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Disease Activity Score Based on 28-Joint Count (DAS28)
Aikaikkuna: Weeks 0, 4, 8, 12, 16, 20, and 24
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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
Aikaikkuna: 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
Aikaikkuna: Weeks 0, 4, 8, 12, 16, 20, and 24
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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).
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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
Aikaikkuna: Weeks 0, 4, 8, 12, 16, 20, and 24
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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
Aikaikkuna: Weeks 4, 8, 12, 16, 20, and 24
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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
Aikaikkuna: Weeks 4, 8, 12, 16, 20, and 24
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CRP (milligrams/Liter) is a mediator of inflammation, acute phase protein.
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Weeks 4, 8, 12, 16, 20, and 24
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Erythrocyte Sedimentation Rate
Aikaikkuna: Weeks 4, 8, 12, 16, 20, and 24
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ESR (mm/hr) is used to determine the acute phase response.
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Weeks 4, 8, 12, 16, 20, and 24
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Yhteistyökumppanit ja tutkijat
Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.
Sponsori
Opintojen ennätyspäivät
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Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Lauantai 31. lokakuuta 2009
Ensisijainen valmistuminen (Todellinen)
Maanantai 14. helmikuuta 2011
Opintojen valmistuminen (Todellinen)
Maanantai 14. helmikuuta 2011
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Torstai 15. lokakuuta 2009
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Torstai 15. lokakuuta 2009
Ensimmäinen Lähetetty (Arvio)
Perjantai 16. lokakuuta 2009
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Torstai 29. maaliskuuta 2018
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Keskiviikko 28. helmikuuta 2018
Viimeksi vahvistettu
Torstai 1. helmikuuta 2018
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
Muut tutkimustunnusnumerot
- ML22665
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