A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Failed on One Prior Anti-TNF Therapy (RESET)
6 juli 2017 uppdaterad av: Hoffmann-La Roche
Rituximab Phase IIIb Open-label, Multi-centre Assessment of Safety and Effectiveness in Patients With RA Following an Inadequate Response to One Prior Anti-TNF Inhibitor (RESET)
This study will evaluate the safety and effectiveness of MabThera (rituximab) in patients with active rheumatoid arthritis who are receiving methotrexate, and who have a previous or current inadequate response to one prior anti-TNF therapy.
All patients will receive MabThera 1000 mg as an intravenous infusion on days 1 and 15.
After the initial study phase of 24 weeks, eligible patients may receive one re-treatment with MabThera.
The anticipated time on study treatment is 48 weeks.
Studieöversikt
Studietyp
Interventionell
Inskrivning (Faktisk)
120
Fas
- Fas 3
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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Alberta
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Edmonton, Alberta, Kanada, T6G 2B7
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Edmonton, Alberta, Kanada, T5M 0H4
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British Columbia
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Kelowna, British Columbia, Kanada, V1Y 3G8
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Vancouver, British Columbia, Kanada, V5Z 3Y1
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Victoria, British Columbia, Kanada, V8V 3P9
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Manitoba
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Winnipeg, Manitoba, Kanada, R3A 1M4
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Newfoundland and Labrador
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St John's, Newfoundland and Labrador, Kanada, A1A 5E8
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St John's, Newfoundland and Labrador, Kanada, A1C 5B8
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Ontario
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Hamilton, Ontario, Kanada, L8N 1Y2
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Hamilton, Ontario, Kanada, L8S 4J9
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Mississauga, Ontario, Kanada, L5M 2V8
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Nepean, Ontario, Kanada, K2G 6E2
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Ottawa, Ontario, Kanada, K1H 8L6
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Ottawa, Ontario, Kanada, K1S 1C2
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Thunder Bay, Ontario, Kanada, P7B 5G3
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Toronto, Ontario, Kanada, M4K 1N2
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Toronto, Ontario, Kanada, M5T 2S8
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Toronto, Ontario, Kanada, M5G 1X5
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Windsor, Ontario, Kanada, N8X 5A6
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Quebec
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Laval, Quebec, Kanada, H7G 2E6
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Montreal, Quebec, Kanada, H1T 2M4
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Montreal, Quebec, Kanada, H3T 1E2
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Montreal, Quebec, Kanada, H2L 1S6
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Montreal, Quebec, Kanada, H2L 4M1
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Quebec City, Quebec, Kanada, G1V 3M7
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Sainte-foy, Quebec, Kanada, G1W 4R4
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Sherbrooke, Quebec, Kanada, J1H 5N4
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St-eustache, Quebec, Kanada, J7P 4J2
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Trois-rivieres, Quebec, Kanada, G8Z 1Y2
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Boras, Sverige, 50182
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Falun, Sverige, 79182
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Goeteborg, Sverige, 41345
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Jonkoping, Sverige, 551 85
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Kalmar, Sverige, 39185
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Karlskrona, Sverige, 37185
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Lulea, Sverige, 97180
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Malmoe, Sverige, 20502
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Oskarstroem, Sverige, 31392
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Skoevde, Sverige, 54185
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Stockholm, Sverige, 18288
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Sundsvall, Sverige, 85186
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år till 80 år (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
Inclusion Criteria:
- Adult patients, 18-80 years of age
- Moderate to severe active rheumatoid arthritis
- Inadequate response to a single previous or current treatment with an anti-TNF agent
- Methotrexate for at least 12 weeks, at a stable dose over the past 4 weeks
Exclusion Criteria:
- Previous treatment with MabThera
- Use of an anti-TNF agent within past 8 weeks (4 in the case of etanercept)
- Concurrent treatment with any Disease Modifying Anti-Rheumatic Drug (DMARD) other than methotrexate
- Active infection, or history of serious or chronic infection
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
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Experimentell: Enkelarm
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1000 mg intravenously on Days 1 and 15
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary
Tidsram: Days 1, 2, 15, and 16 and Week 48 of Initial treatment period
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Percentage of participants who reported an AE or serious AE (SAE), a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died.
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Days 1, 2, 15, and 16 and Week 48 of Initial treatment period
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary
Tidsram: Days 1, 2, 15, and 16 and Week 48 of Re-treatment period
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Percentage of participants who reported an AE or SAE, a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died.
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Days 1, 2, 15, and 16 and Week 48 of Re-treatment period
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Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period
Tidsram: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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ACR20/50/70, defined as ≥20 percent (%), 50%, or 70% improvement, respectively, compared to baseline in tender joint count (TJC) and swollen joint count (SJC), and 20%/50%/70% improvement in at least 3 of 5 additional ACR core set variables: Patient Assessment of Pain; Patient's Global Assessment of Disease Activity; Physician's Global Assessment of Disease Activity; Health Assessment Questionnaire - Disability Index (HAQ-DI); and an acute phase reactant (erythrocyte sedimentation rate [ESR] or C-Reactive Protein [CRP]).
If CRP was missing or not done, then ESR was used.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Initial Treatment Period
Tidsram: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Complete clinical response was defined as having an ACR70 for at least 13 weeks.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period
Tidsram: Weeks 12 and 24 of Re-treatment period
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ACR20/50/70, defined as ≥20%, 50%, or 70% improvement, respectively, compared to baseline in TJC and SJC, and 20%/50%/70% improvement in at least 3 of 5 additional ACR core set variables: Patient Assessment of Pain; Patient's Global Assessment of Disease Activity; Physician's Global Assessment of Disease Activity; HAQ-DI; and an acute phase reactant (ESR or CRP).
If CRP was missing or not done, then ESR was used.
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Weeks 12 and 24 of Re-treatment period
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Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Re-Treatment Period
Tidsram: Weeks 12 and 24 of Re-treatment period
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Complete clinical response was defined as having an ACR70 for at least 13 weeks.
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Weeks 12 and 24 of Re-treatment period
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Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period
Tidsram: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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The EULAR response criteria were based on the assessment of disease activity using the DAS28.
The EULAR response criteria included not only change in disease activity but current disease activity.
To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity.
There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none.
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR.
The DAS28 has a continuous scale ranging from 0 to 9.4.
The level of disease activity was interpreted as low (DAS28 score less than or equal to [≤]3.2), moderate (DAS28 score greater than [>]3.2 but ≤5.1), or high (DAS28 score >5.1).
A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period
Tidsram: Weeks 12 and 24 of Re-treatment period
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The EULAR response criteria were based on the assessment of disease activity using the DAS28.
The EULAR response criteria included not only change in disease activity but current disease activity.
To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity.
There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none.
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR.
The DAS28 has a continuous scale ranging from 0 to 9.4.
The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1).
A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
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Weeks 12 and 24 of Re-treatment period
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Change From Baseline in DAS28 During the Initial Treatment Period
Tidsram: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR.
The DAS28 has a continuous scale ranging from 0 to 9.4.
The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1).
A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
A change of 1.2 units in DAS28 in an individual participant was considered a significant change.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Change From Baseline in DAS28 During the Re-Treatment Period
Tidsram: Weeks 12 and 24 of Re-treatment period
|
The DAS28 scoring used 4 core components: SJC, TJC, Patient Global Assessment of Disease Activity, and ESR.
The DAS28 has a continuous scale ranging from 0 to 9.4.
The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1).
A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
A change of 1.2 units in DAS28 in an individual participant was considered a significant change.
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Weeks 12 and 24 of Re-treatment period
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Change From Baseline in SJC During the Initial Treatment Period
Tidsram: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Change From Baseline in SJC During the Re-Treatment Period
Tidsram: Weeks 12 and 24 of Re-treatment period
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Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
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Weeks 12 and 24 of Re-treatment period
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Change From Baseline in TJC During the Initial Treatment Period
Tidsram: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Change From Baseline in TJC During the Re-Treatment Period
Tidsram: Weeks 12 and 24 of Re-treatment period
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Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
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Weeks 12 and 24 of Re-treatment period
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Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period
Tidsram: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Physician Global Assessment of Disease Activity was measured using a 100-mm visual analog scale (VAS) where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity.
The physician marked the line and the distance from the left edge was measured in mm.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Change From Baseline in Physician's Global Assessment of Disease Activity During the Re-Treatment Period
Tidsram: Weeks 12 and 24 of Re-treatment period
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Physician Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity.
The physician marked the line and the distance from the left edge was measured in mm.
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Weeks 12 and 24 of Re-treatment period
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Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period
Tidsram: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
Patient Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity.
The participant was asked to marked the line and the distance from the left edge was measured in mm.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Change From Baseline in Patient Global Assessment of Disease Activity During the Re-Treatment Period
Tidsram: Weeks 12 and 24 of Re-treatment period and Week 4 after last maintenance
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Patient Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity.
The participant was asked to marked the line and the distance from the left edge was measured in mm.
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Weeks 12 and 24 of Re-treatment period and Week 4 after last maintenance
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Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period
Tidsram: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
Patient Global Assessment of Pain was measured using a 100-mm VAS where the extreme left end of the line was 0 = no pain and the extreme right end of the line was 100 = unbearable pain.
The participant was asked to mark the line and the distance from the left edge was measured in mm.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
|
Change From Baseline in Patient Global Assessment of Pain During the Re-Treatment Period
Tidsram: Weeks 12 and 24 of Re-treatment period
|
Patient Global Assessment of Pain was measured using a 100-mm VAS where the extreme left end of the line was 0 = no pain and the extreme right end of the line was 100 = unbearable pain.
The participant was asked to mark the line and the distance from the left edge was measured in mm.
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Weeks 12 and 24 of Re-treatment period
|
|
Change From Baseline HAQ-DI Score During the Initial Treatment Period
Tidsram: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
HAQ-DI: 20 questions, 8 categories of functioning: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common usual activities.
Participants report amount of difficulty in performing 2-3 specific subcategory items.
Difficulty score is from 0 to 3 (0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; and 3 = unable to do).
The highest component score in each of the 8 categories determined the score for that category, unless aids, devices, and/or help from another person were required which = a score of 2 (unless already 2 or 3).
The 8 category scores were averaged into overall HAQ-DI score ranging from 0 to 3 (0 to 1 = mild to moderate difficulty; 1 to 2 = moderate to severe disability; and 2 to 3 = severe to very severe disability).
HAQ-DI not computed if > 2 categories were missing.
|
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
|
Change From Baseline HAQ-DI Score During the Re-Treatment Period
Tidsram: Weeks 12 and 24 of Re-treatment period
|
HAQ-DI: 20 questions, 8 categories of functioning: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common usual activities.
Participants report amount of difficulty in performing 2-3 specific subcategory items.
Difficulty score is from 0 to 3 (0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; and 3 = unable to do).
The highest component score in each of the 8 categories determines the score for that category, unless aids, devices, and/or help from another person were required which = a score of 2 (unless already 2 or 3).
The 8 category scores were averaged into overall HAQ-DI score ranging from 0 to 3 (0 to 1 = mild to moderate difficulty; 1 to 2 = moderate to severe disability; and 2 to 3 = severe to very severe disability).
HAQ-DI not computed if >2 categories were missing.
|
Weeks 12 and 24 of Re-treatment period
|
|
Change From Baseline in ESR During the Initial Treatment Period
Tidsram: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
ESR was measured in mm/hour and was used to determine the acute phase response.
Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
|
Change From Baseline in ESR During the Re-Treatment Period
Tidsram: Weeks 12 and 24 of Re-treatment period
|
ESR was measured in mm/hour and was used to determine the acute phase response.
Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr.
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Weeks 12 and 24 of Re-treatment period
|
|
Change From Baseline in CRP During the Initial Treatment Period
Tidsram: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
CRP levels were measured in milligrams/liter (mg/L) and were used to determine the acute phase response.
A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
|
Change From Baseline CRP During the Re-Treatment Period
Tidsram: Weeks 12 and 24 of Re-treatment period
|
CRP levels were measured in mg/L and were used to determine the acute phase response.
A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L.
|
Weeks 12 and 24 of Re-treatment period
|
|
Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period
Tidsram: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR.
The DAS28 has a continuous scale ranging from 0 to 9.4.
The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1).
A DAS28 score ≤2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
|
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
|
Percentage of Participants With Disease Remission According to DAS28 in the Re-Treatment Period
Tidsram: Weeks 12 and 24 of Re-treatment period
|
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR.
The DAS28 has a continuous scale ranging from 0 to 9.4.
The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1).
A DAS28 score ≤2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
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Weeks 12 and 24 of Re-treatment period
|
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Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period
Tidsram: Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
Participant fatigue was evaluated using the FACIT-F scale, a 13-item questionnaire in which the participants were requested to score each item on a 5-point scale.
The FACIT-F scores ranged from 0 to 52, with higher scores representing less fatigue.
Score changes of 4 points or more were considered clinically meaningful.
The total score was a summation of all 13 items, where 2 of the positive items (I have energy; I am able to do my usual activities) were reversed for scoring.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Change From Baseline in FACIT-F Total Score During the Re-Treatment Period
Tidsram: Weeks 12 and 24 of Re-treatment period
|
Participant fatigue was evaluated using the FACIT-F scale, a 13-item questionnaire in which the participants were requested to score each item on a 5-point scale.
The FACIT-F scores ranged from 0 to 52, with higher scores representing less fatigue.
Score changes of 4 points or more were considered clinically meaningful.
The total score was a summation of all 13 items, where 2 of the positive items (I have energy; I am able to do my usual activities) were reversed for scoring.
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Weeks 12 and 24 of Re-treatment period
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Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
18 juli 2006
Primärt slutförande (Faktisk)
12 mars 2009
Avslutad studie (Faktisk)
12 mars 2009
Studieregistreringsdatum
Först inskickad
7 januari 2011
Först inskickad som uppfyllde QC-kriterierna
7 januari 2011
Första postat (Uppskatta)
10 januari 2011
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
15 augusti 2017
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
6 juli 2017
Senast verifierad
1 juni 2017
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- ML20381
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