A Study to Assess Efficacy With Respect to Clinical Improvement in Disease Activity and Safety of Tocilizumab in Patients Wtih Active Rheumatoid Arthritis.
14. ledna 2016 aktualizováno: Hoffmann-La Roche
"Effectiveness After Four and Twentyfour Weeks and Safety of Tocilizumab in Patients With Active RA"
This single arm study will assess the effectiveness of tocilizumab in combination with traditional DMARDs with regard to the clinical improvement in disease activity (achievement of LDAS) after 24 weeks' treatment in patients with active rheumatoid arthritis (RA) who have had an inadequate response to current traditional DMARD and/or anti-TNF therapy.
Patients will receive tocilizumab 8mg/kg iv every 4 weeks, in addition to ongoing DMARDs at the stable pre-entry dose prescribed by the physician, for a total of 6 infusions during the regular treatment period and a further 6 infusions during an optional extension phase.
The anticipated time on study treatment is 6 to 12 months, and the target sample size is <500 individuals.
Přehled studie
Typ studie
Intervenční
Zápis (Aktuální)
286
Fáze
- Fáze 3
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Aachen, Německo, 52064
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Bad Abbach, Německo, 93077
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Bad Aibling, Německo, 83043
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Bad Bramstedt, Německo, 24576
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Bad Nauheim, Německo, 61231
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Baden-baden, Německo, 76530
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Bayreuth, Německo, 95445
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Berlin, Německo, 10117
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Berlin, Německo, 13125
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Berlin, Německo, 13055
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Berlin, Německo, 14163
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Berlin, Německo, 12435
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Berlin, Německo, 14109
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Berlin, Německo, 12161
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Bremen, Německo, 28199
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Cuxhaven, Německo, 27476
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Damp, Německo, 24351
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Donaueschingen, Německo, 78166
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Dresden, Německo, 01307
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Dresden, Německo, 01067
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Dresden, Německo, 01109
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Düsseldorf, Německo, 40225
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Düsseldorf, Německo, 40217
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Erfurt, Německo, 99096
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Erlangen, Německo, 91054
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Erlangen, Německo, 91056
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Essen, Německo, 45239
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Frankfurt, Německo, 60596
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Frankfurt Am Main, Německo, 60590
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Fulda, Německo, 36039
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Gommern, Německo, 39245
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Goslar, Německo, 38642
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Grafschaft, Německo, 53501
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Göttingen, Německo, 37075
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Hagen, Německo, 58135
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Halle, Německo, 06120
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Halle, Německo, 06108
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Hamburg, Německo, 22081
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Hamburg, Německo, 22767
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Hamburg, Německo, 22147
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Hamburg, Německo, 22609
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Hannover, Německo, 30625
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Heidelberg, Německo, 69120
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Herne, Německo, 44652
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Hildesheim, Německo, 31134
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Hofheim, Německo, 65719
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Homburg/saar, Německo, 66424
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Hoyerswerda, Německo, 02977
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Köln, Německo, 50924
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Köln, Německo, 50679
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Leipzig, Německo, 04103
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Ludwigsfelde, Německo, 14974
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Ludwigshafen, Německo, 67063
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Lüneburg, Německo, 21335
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Mainz, Německo, 55131
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Mainz, Německo, 55122
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Marburg, Německo, 35037
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Muenchen, Německo, 80336
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München, Německo, 81541
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München, Německo, 81925
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München, Německo, 80335
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Münster, Německo, 48149
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Naunhof, Německo, 04683
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Neuss, Německo, 41460
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Nürnberg, Německo, 90402
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Oberammergau, Německo, 82487
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Osnabrück, Německo, 49074
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Pirna, Německo, 01796
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Plochingen, Německo, 73207
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Potsdam, Německo, 14469
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Ratingen, Německo, 40882
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Rostock, Německo, 18059
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Sendenhorst, Německo, 48324
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Stuttgart, Německo, 70178
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Stuttgart, Německo, 70372
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Treuenbrietzen, Německo, 14929
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Tübingen, Německo, 72076
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ULM, Německo, 89081
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Wiesbaden, Německo, 65189
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Würselen, Německo, 52146
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Zeven, Německo, 27404
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let a starší (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
Inclusion Criteria:
- adult patients, >=18 years of age;
- rheumatoid arthritis of >=6 months duration diagnosed according to the revised 1987 ACR criteria;
- DAS28 of >3.2;
- At screening either ESR >=28 mm/h or CRP >=1 mg/dL;
- Having received permitted DMARDs, 1 or more; current DMARD therapy must have been at a stable dose for at least 8 weeks prior to baseline.
Exclusion Criteria:
- major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following screening;
- functional class IV as identified by the ACR classification of functional status in RA;
- rheumatoid autoimmune disease other than RA;
- prior history of or current inflammatory joint disease other than RA.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: Tocilizumab
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8mg/kg iv every 4 weeks
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Percentage of Participants With Low Disease Activity Score at Week 24
Časové okno: Week 24
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Low Disease Activity Score (LDAS) is defined as Disease Activity score less than or equal to (≤ ) 3.2.
Disease activity score 28 (DAS28) was 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 100-mm Visual analog scale [VAS]); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity.
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Week 24
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Absolute Changes in DAS28 From Baseline
Časové okno: Weeks 1, 2, 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 100-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity.
DAS28 ≤3.2 = low disease activity, DAS28 greater than (>)3.2 to 5.1 = moderate to high disease activity.
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Weeks 1, 2, 4, 8, 12, 16, 20 and 24
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Percentage of Participants With a Response at Week 24 by European League Against Rheumatism (EULAR) Category
Časové okno: Week 24
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The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached.
Good responders: change from baseline >1.2 with DAS28 ≤3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to ≤5.1 or change from baseline >0.6 to ≤1.2 with DAS28 ≤5.1; non-responders: change from baseline ≤ 0.6 or change from baseline >0.6 and ≤1.2 with DAS28 >5.1.
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Week 24
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Percentage of Participants With a DAS28 Response at Weeks 4 and 24
Časové okno: Weeks 4 and 24
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DAS28 calculated from the number of swollen joints and painful joints using the 28-joint count, the ESR and participant's global assessment (PGA) of disease activity (participant rated arthritis activity assessment using VAS) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity.
DAS28 ≤3.2 = low disease activity, DAS28 <2.6 = remission and a clinically significant (CS) reduction was defined as ≥1.2.
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Weeks 4 and 24
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Percentage of Participants With an American College of Rheumatology 20%, 50%, or 70% (ACR20/ACR50/ACR70) Response
Časové okno: Weeks 1, 2, 4, 8, 12, 16, 20 and 24
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ACR20/50/70 response: ≥20%, 50%, or 70% improvement, respectively, in swollen and tender joint count; and ≥20% improvement 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 Health Assessment Questionnaire [HAQ-DI]); and C-Reactive Protein (CRP).
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Weeks 1, 2, 4, 8, 12, 16, 20 and 24
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Change From Baseline in Swollen and Tender Joint Counts at Week 24
Časové okno: Week 24
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Swollen joint count: 66 joints were assessed for swelling and joints were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. Tender joint counts: 68 joints were assessed for tenderness and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 68. |
Week 24
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Change From Baseline in the Levels of C-Reactive Protein at Week 24
Časové okno: Week 24
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The serum concentration of CRP is measured in mg/L.
A reduction in the level was considered an improvement.
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Week 24
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Change From Baseline in Participant's Global Assessment of Pain (VAS) at Week 24
Časové okno: Week 24
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Participant's global assessment of pain was assessed using a 100-mm horizontal VAS (0 to 100 mm) with 0=pain absent and 100=unbearable pain.
Participants responded by placing a mark on the line to indicate their current level of pain.
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Week 24
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Change From Baseline in Participant and Physician Assessment of Global Disease Activity (VAS) at Week 24
Časové okno: Week 24
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Participant's global assessment of disease activity was an overall assessment of their current disease activity on a 100-mm horizontal VAS scale (left-hand extreme: "no disease activity"; right-hand extreme: "maximum disease activity"). Physician's global assessment of disease activity was measured as participant's current disease activity on a 100-mm horizontal VAS scale (left hand extreme: "no disease activity"; right-hand extreme: "maximum disease activity"). |
Week 24
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Change From Baseline in Clinical Disease Activity Index (CDAI) Score
Časové okno: Weeks 1, 2, 4, 8, 12, 16, 20 and 24
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CDAI was calculated according to the following formula: CDAI = Number of swollen joints (plus) + Number of tender joints + VAS disease activity participant assessment + VAS disease activity investigator assessment. The maximum score was 334 (66 joints + 68 joints + 100 mm + 100 mm); higher scores indicated higher disease activity. |
Weeks 1, 2, 4, 8, 12, 16, 20 and 24
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Change From Baseline in HAQ-DI at Week 24
Časové okno: Week 24
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HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week.
Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do.
Overall score was computed as the sum of domain scores and divided by the number of domains answered.
Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
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Week 24
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Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 24
Časové okno: Week 24
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FACIT-F is a 13-item questionnaire.
Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much).
The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue.
For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response).
The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).
A higher score reflects an improvement in the participant's health status.
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Week 24
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Change From Baseline in Short Form-36 (SF-36) Score at Week 24
Časové okno: Week 24
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SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health.
The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
Absolute change was defined as the change from baseline to Week 24.
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Week 24
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Participant's Global Assessment of Pain as Assessed by Patient Take Home Form (PTHF)
Časové okno: Baseline and Weeks 1, 2, and 4
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Participant's were asked to state the worst level of pain felt in the past 24 hours using a 100-mm horizontal VAS (0 to 100 mm) with 0=no pain and 100=unbearable pain.
Participants responded by placing a mark on the line to indicate their level of pain.
Participants were asked to document their response during the first 4 treatment weeks at approximately the same time every day.
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Baseline and Weeks 1, 2, and 4
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Duration of Morning Stiffness as Assessed Using PTHF
Časové okno: Baseline, Weeks 1, 2, and 4
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Duration of morning stiffness: participants were asked 'how long did your morning stiffness last from the time you woke up yesterday' and the response was provided in minutes and hours.
Participants were asked to document their response during the first 4 treatment weeks at approximately the same time every day.
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Baseline, Weeks 1, 2, and 4
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Participant Assessment of Fatigue/Tiredness as Assessed Using PTHF
Časové okno: Baseline and Weeks 1, 2 and 4
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Participants were asked to assess their overall level of fatigue/tiredness during the previous 24 hours using a 100-mm horizontal VAS with 0=none and 100=very severe.
Participants responded by placing a mark on the line to indicate their current level of fatigue.
Participants were asked to document their response during the first 4 treatment weeks at approximately the same time every day.
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Baseline and Weeks 1, 2 and 4
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Treatment Satisfaction Questionnaire for Medication (TSQM) Score
Časové okno: Week 24
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The TSQM is a general measure of participants treatment satisfaction and consists of 14 questions that result in 4 subscales: "effectiveness", "side-effects", "convenience" and "global satisfaction".
All subscale scores range from 0 to 100%, with 100% being the best possible result.
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Week 24
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Changes in Hemoglobin
Časové okno: Baseline, Weeks 1, 2, 4 and 24
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Hemoglobin levels were determined as a hematology parameter to measure changes in disease related anemia.
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Baseline, Weeks 1, 2, 4 and 24
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Changes in C-Reactive Protein
Časové okno: Baseline, Weeks 1, 2 ,4 and 24
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CRP is an acute phase inflammatory marker used as a measure of inflammation.
A reduction in CRP is considered to be an improvement.
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Baseline, Weeks 1, 2 ,4 and 24
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Changes in Erythrocyte Sedimentation Rate (ESR)
Časové okno: Baseline, Weeks 1, 2, 4 and 24
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ESR is an inflammation marker used to determine acute phase response.
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Baseline, Weeks 1, 2, 4 and 24
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Percentage of Participants Withdrawing From Study Treatment Because of Insufficient Therapeutic Response
Časové okno: Weeks 1, 2, 4, 8, 12, 16, 20 and 24
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Participants who withdrew from study drug due to other reasons were not taken into account.
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Weeks 1, 2, 4, 8, 12, 16, 20 and 24
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia
1. srpna 2008
Primární dokončení (Aktuální)
1. listopadu 2009
Dokončení studie (Aktuální)
1. listopadu 2009
Termíny zápisu do studia
První předloženo
17. září 2008
První předloženo, které splnilo kritéria kontroly kvality
17. září 2008
První zveřejněno (Odhad)
18. září 2008
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
8. února 2016
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
14. ledna 2016
Naposledy ověřeno
1. ledna 2016
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- ML21469
- 2008-000105-11
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
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