A Study to Assess Efficacy With Respect to Clinical Improvement in Disease Activity and Safety of Tocilizumab in Patients Wtih Active Rheumatoid Arthritis.
torstai 14. tammikuuta 2016 päivittänyt: 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.
Tutkimuksen yleiskatsaus
Opintotyyppi
Interventio
Ilmoittautuminen (Todellinen)
286
Vaihe
- Vaihe 3
Yhteystiedot ja paikat
Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.
Opiskelupaikat
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Aachen, Saksa, 52064
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Bad Abbach, Saksa, 93077
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Bad Aibling, Saksa, 83043
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Bad Bramstedt, Saksa, 24576
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Bad Nauheim, Saksa, 61231
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Baden-baden, Saksa, 76530
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Bayreuth, Saksa, 95445
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Berlin, Saksa, 10117
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Berlin, Saksa, 13125
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Berlin, Saksa, 13055
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Berlin, Saksa, 14163
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Berlin, Saksa, 12435
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Berlin, Saksa, 14109
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Berlin, Saksa, 12161
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Bremen, Saksa, 28199
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Cuxhaven, Saksa, 27476
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Damp, Saksa, 24351
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Donaueschingen, Saksa, 78166
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Dresden, Saksa, 01307
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Dresden, Saksa, 01067
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Dresden, Saksa, 01109
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Düsseldorf, Saksa, 40225
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Düsseldorf, Saksa, 40217
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Erfurt, Saksa, 99096
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Erlangen, Saksa, 91054
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Erlangen, Saksa, 91056
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Essen, Saksa, 45239
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Frankfurt, Saksa, 60596
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Frankfurt Am Main, Saksa, 60590
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Fulda, Saksa, 36039
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Gommern, Saksa, 39245
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Goslar, Saksa, 38642
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Grafschaft, Saksa, 53501
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Göttingen, Saksa, 37075
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Hagen, Saksa, 58135
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Halle, Saksa, 06120
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Halle, Saksa, 06108
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Hamburg, Saksa, 22081
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Hamburg, Saksa, 22767
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Hamburg, Saksa, 22147
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Hamburg, Saksa, 22609
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Hannover, Saksa, 30625
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Heidelberg, Saksa, 69120
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Herne, Saksa, 44652
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Hildesheim, Saksa, 31134
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Hofheim, Saksa, 65719
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Homburg/saar, Saksa, 66424
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Hoyerswerda, Saksa, 02977
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Köln, Saksa, 50924
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Köln, Saksa, 50679
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Leipzig, Saksa, 04103
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Ludwigsfelde, Saksa, 14974
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Ludwigshafen, Saksa, 67063
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Lüneburg, Saksa, 21335
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Mainz, Saksa, 55131
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Mainz, Saksa, 55122
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Marburg, Saksa, 35037
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Muenchen, Saksa, 80336
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München, Saksa, 81541
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München, Saksa, 81925
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München, Saksa, 80335
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Münster, Saksa, 48149
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Naunhof, Saksa, 04683
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Neuss, Saksa, 41460
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Nürnberg, Saksa, 90402
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Oberammergau, Saksa, 82487
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Osnabrück, Saksa, 49074
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Pirna, Saksa, 01796
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Plochingen, Saksa, 73207
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Potsdam, Saksa, 14469
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Ratingen, Saksa, 40882
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Rostock, Saksa, 18059
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Sendenhorst, Saksa, 48324
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Stuttgart, Saksa, 70178
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Stuttgart, Saksa, 70372
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Treuenbrietzen, Saksa, 14929
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Tübingen, Saksa, 72076
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ULM, Saksa, 89081
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Wiesbaden, Saksa, 65189
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Würselen, Saksa, 52146
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Zeven, Saksa, 27404
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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;
- 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.
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 käytössä
- Inventiomalli: Yksittäinen ryhmätehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Kokeellinen: Tosilitsumabi
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8mg/kg iv every 4 weeks
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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Percentage of Participants With Low Disease Activity Score at Week 24
Aikaikkuna: 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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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Absolute Changes in DAS28 From Baseline
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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)
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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)
Aikaikkuna: 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
Aikaikkuna: 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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Yhteistyökumppanit ja tutkijat
Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.
Sponsori
Opintojen ennätyspäivät
Nämä päivämäärät seuraavat ClinicalTrials.gov-sivustolle lähetettyjen tutkimustietueiden ja yhteenvetojen edistymistä. National Library of Medicine (NLM) tarkistaa tutkimustiedot ja raportoidut tulokset varmistaakseen, että ne täyttävät tietyt laadunvalvontastandardit, ennen kuin ne julkaistaan julkisella verkkosivustolla.
Opi tärkeimmät päivämäärät
Opiskelun aloitus
Perjantai 1. elokuuta 2008
Ensisijainen valmistuminen (Todellinen)
Sunnuntai 1. marraskuuta 2009
Opintojen valmistuminen (Todellinen)
Sunnuntai 1. marraskuuta 2009
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Keskiviikko 17. syyskuuta 2008
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Keskiviikko 17. syyskuuta 2008
Ensimmäinen Lähetetty (Arvio)
Torstai 18. syyskuuta 2008
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Arvio)
Maanantai 8. helmikuuta 2016
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Torstai 14. tammikuuta 2016
Viimeksi vahvistettu
Perjantai 1. tammikuuta 2016
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
Muut tutkimustunnusnumerot
- ML21469
- 2008-000105-11
Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .
Kliiniset tutkimukset Nivelreuma
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