A Study of Adalimumab in Japanese Subjects With Rheumatoid Arthritis
1 août 2012 mis à jour par: Abbott
A Phase 3 Multi-Center, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study Comparing Adalimumab and Placebo in Adult Japanese Subjects With Rheumatoid Arthritis
To evaluate the potential of adalimumab to inhibit radiographic progression in joint destruction compared with placebo in adult Japanese subjects with recent onset of rheumatoid arthritis.
Aperçu de l'étude
Statut
Complété
Les conditions
Description détaillée
This was a Phase 3 multicenter, randomized, double-blind, parallel group, placebo-controlled study designed to evaluate the inhibition of radiographic progression by adalimumab compared with placebo in adult Japanese patients with early rheumatoid arthritis (RA) who had not been previously treated with methotrexate (MTX).
Eligible participants were randomized 1:1 to receive either a subcutaneous injection of adalimumab 40 mg or matching placebo every other week (eow) during the 26-week double-blind phase.
All participants also received 6 mg to 8 mg MTX weekly as basal treatment for their disease.
Participants who experienced an increase in disease activity (more than 20% increase in tender joint count and swollen joint count) at Week 12, 16, or 20 compared with Baseline after having increased MTX dose to 8 mg per week for at least 4 weeks were discontinued from the double-blind phase and were eligible to receive open-label adalimumab 40 mg eow as rescue treatment.
Participants who completed the 26 weeks of treatment (either double-blind study drug [adalimumab or placebo] treatment or open-label adalimumab treatment) were eligible to enter the 26-week open-label phase in which they received adalimumab 40 mg eow.
Efficacy and safety assessments were performed at Baseline and at designated study visits.
Type d'étude
Interventionnel
Inscription (Réel)
334
Phase
- Phase 3
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Anjo, Japon
- Site Reference ID/Investigator# 46861
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Aomori, Japon
- Site Reference ID/Investigator# 46919
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Chiba, Japon
- Site Reference ID/Investigator# 46805
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Chiba, Japon
- Site Reference ID/Investigator# 46806
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Chiba, Japon
- Site Reference ID/Investigator# 46880
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Chiba, Japon
- Site Reference ID/Investigator# 46881
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Fuchu, Japon
- Site Reference ID/Investigator# 46890
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Fukuoka, Japon
- Site Reference ID/Investigator# 46902
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Fukuoka, Japon
- Site Reference ID/Investigator# 46903
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Fukuoka, Japon
- Site Reference ID/Investigator# 46904
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Gifu, Japon
- Site Reference ID/Investigator# 46856
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Gunma, Japon
- Site Reference ID/Investigator# 46944
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Hiroshima, Japon
- Site Reference ID/Investigator# 46893
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Hiroshima, Japon
- Site Reference ID/Investigator# 46894
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Hokkaido, Japon
- Site Reference ID/Investigator# 12161
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Hokkaido, Japon
- Site Reference ID/Investigator# 46916
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Hokkaido, Japon
- Site Reference ID/Investigator# 46918
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Hyogo, Japon
- Site Reference ID/Investigator# 46865
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Hyogo, Japon
- Site Reference ID/Investigator# 46871
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Ibaraki, Japon
- Site Reference ID/Investigator# 46801
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Ibaraki, Japon
- Site Reference ID/Investigator# 46925
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Iwate, Japon
- Site Reference ID/Investigator# 46800
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Kagoshima, Japon
- Site Reference ID/Investigator# 46873
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Kagoshima, Japon
- Site Reference ID/Investigator# 46874
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Kanagawa, Japon
- Site Reference ID/Investigator# 46845
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Kanagawa, Japon
- Site Reference ID/Investigator# 46899
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Kanagawa, Japon
- Site Reference ID/Investigator# 46901
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Kanazawa, Japon
- Site Reference ID/Investigator# 46851
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Kanazawa, Japon
- Site Reference ID/Investigator# 46852
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Kawagoe, Japon
- Site Reference ID/Investigator# 46802
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Kawasaki, Japon
- Site Reference ID/Investigator# 46900
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Kirishima, Japon
- Site Reference ID/Investigator# 46875
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Kitakyushu, Japon
- Site Reference ID/Investigator# 46870
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Kumamoto, Japon
- Site Reference ID/Investigator# 46872
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Kumamoto, Japon
- Site Reference ID/Investigator# 46912
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Kyoto, Japon
- Site Reference ID/Investigator# 46864
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Maebashi, Japon
- Site Reference ID/Investigator# 46943
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Matsuyama, Japon
- Site Reference ID/Investigator# 46898
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Miyazaki, Japon
- Site Reference ID/Investigator# 46915
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Nagano, Japon
- Site Reference ID/Investigator# 46853
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Nagano, Japon
- Site Reference ID/Investigator# 46855
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Nagasaki, Japon
- Site Reference ID/Investigator# 46909
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Nagasaki, Japon
- Site Reference ID/Investigator# 46910
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Nagasaki, Japon
- Site Reference ID/Investigator# 46911
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Nagoya, Japon
- Site Reference ID/Investigator# 46858
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Nagoya, Japon
- Site Reference ID/Investigator# 46860
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Nara, Japon
- Site Reference ID/Investigator# 46877
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Nara, Japon
- Site Reference ID/Investigator# 46885
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Niigata, Japon
- Site Reference ID/Investigator# 46848
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Niigata, Japon
- Site Reference ID/Investigator# 46906
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Oita, Japon
- Site Reference ID/Investigator# 46914
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Okayama, Japon
- Site Reference ID/Investigator# 46869
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Okayama, Japon
- Site Reference ID/Investigator# 46886
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Okayama, Japon
- Site Reference ID/Investigator# 46887
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Okayama, Japon
- Site Reference ID/Investigator# 46892
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Okinawa, Japon
- Site Reference ID/Investigator# 46876
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Osaka, Japon
- Site Reference ID/Investigator# 46946
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Osaka, Japon
- Site Reference ID/Investigator# 46947
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Rifu, Japon
- Site Reference ID/Investigator# 46842
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Sagamihara, Japon
- Site Reference ID/Investigator# 46846
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Saitama, Japon
- Site Reference ID/Investigator# 46803
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Saitama, Japon
- Site Reference ID/Investigator# 46804
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Saitama, Japon
- Site Reference ID/Investigator# 46878
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Saitama, Japon
- Site Reference ID/Investigator# 46879
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Sapporo, Japon
- Site Reference ID/Investigator# 46917
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Shimotsuke, Japon
- Site Reference ID/Investigator# 46942
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Shizuoka, Japon
- Site Reference ID/Investigator# 46854
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Shizuoka, Japon
- Site Reference ID/Investigator# 46857
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Shizuoka, Japon
- Site Reference ID/Investigator# 46859
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Takamatsu, Japon
- Site Reference ID/Investigator# 46895
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Tokyo, Japon
- Site Reference ID/Investigator# 46843
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Tokyo, Japon
- Site Reference ID/Investigator# 46844
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Tokyo, Japon
- Site Reference ID/Investigator# 46850
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Tokyo, Japon
- Site Reference ID/Investigator# 46882
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Tokyo, Japon
- Site Reference ID/Investigator# 46883
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Tokyo, Japon
- Site Reference ID/Investigator# 46884
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Tokyo, Japon
- Site Reference ID/Investigator# 46888
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Tokyo, Japon
- Site Reference ID/Investigator# 46889
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Tokyo, Japon
- Site Reference ID/Investigator# 46891
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Tokyo, Japon
- Site Reference ID/Investigator# 46896
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Toyama, Japon
- Site Reference ID/Investigator# 46849
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Toyama, Japon
- Site Reference ID/Investigator# 46907
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Toyoake, Japon
- Site Reference ID/Investigator# 46862
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Toyohashi, Japon
- Site Reference ID/Investigator# 46866
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Tsu, Japon
- Site Reference ID/Investigator# 46863
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Tsukuba, Japon
- Site Reference ID/Investigator# 46926
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Yokohama, Japon
- Site Reference ID/Investigator# 46897
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Yokohama, Japon
- Site Reference ID/Investigator# 46905
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
20 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria
- Rheumatoid arthritis based on the American College of Rheumatology criteria
- Methotrexate or leflunomide naïve
- Disease duration less than or equal to 2 years from diagnosis
Exclusion Criteria
- History of acute inflammatory joint disease of different origin from rheumatoid arthritis, cancer, lymphoma, leukemia or lymphoproliferative disease, active TB, HIV
- Previously received anti-TNF therapy anti-IL-6 receptor antibody, CTLA4-Ig, anti-CD20 antibody, cyclophosphamide, cyclosporine, azathioprine, or tacrolimus
- Joint surgery involving joints to be assessed within 8 weeks prior to Screening
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Comparateur placebo: DB Placebo
Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for up to 26 weeks.
Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
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Double-blind adalimumab-matching placebo administered subcutaneously (SC)every other week (eow)
Autres noms:
|
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Expérimental: DB adalimumab
Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) for up to 26 weeks.
Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
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Double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow)
Autres noms:
|
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Expérimental: DB Adalimumab/OL Adalimumab
Participants received double-blind adalimumab administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks.
Participants also received concomitant methotrexate 6 to 8 mg administered orally weekly.
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Double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow)
Autres noms:
Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) after completion of the first 26 weeks in the study
Autres noms:
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Expérimental: DB Placebo/OL Adalimumab
Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) for 26 weeks followed by open-label adalimumab 40 mg SC eow for up to 26 weeks.
Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
|
Double-blind adalimumab-matching placebo administered subcutaneously (SC)every other week (eow)
Autres noms:
Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) after completion of the first 26 weeks in the study
Autres noms:
|
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Expérimental: DB Adalimumab/RE OL Adalimumab
Participants received double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible at Week 12 or after) to complete 26 weeks, followed by open-label adalimumab 40 mg SC eow for up to 26 weeks.
Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
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Double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow)
Autres noms:
Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) after completion of the first 26 weeks in the study
Autres noms:
Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) as rescue treatment to complete the first 26 weeks in the study- dependent on participant eligibility (increase in disease activity), applies to Weeks 12 to 26
Autres noms:
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Expérimental: DB Placebo/RE OL Adalimumab
Participants received double-blind placebo administered subcutaneously (SC) every other week (eow) and then open-label adalimumab 40 mg SC eow as rescue treatment (as eligible at Week 12 or after) to complete 26 weeks, followed by open-label adalimumab 40 mg SC eow for up to 26 weeks.
Participants received concomitant methotrexate 6 to 8 mg administered orally weekly.
|
Double-blind adalimumab-matching placebo administered subcutaneously (SC)every other week (eow)
Autres noms:
Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) after completion of the first 26 weeks in the study
Autres noms:
Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) as rescue treatment to complete the first 26 weeks in the study- dependent on participant eligibility (increase in disease activity), applies to Weeks 12 to 26
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Change From Baseline in Modified Total Sharp X-Ray Score at Week 26
Délai: Baseline, Week 26
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Modified Total Sharp Score (mTSS) is a measure of joint health, used in evaluation of inhibition of radiographic progression of disease.
Digitized X-rays of hands and feet were obtained then scored in a blinded manner: for erosions (0 [no damage] to 5 [complete collapse or total destruction of joint]) and for joint space narrowing (0 [no damage] to 4 [complete luxation of joint]).
Scores were added, giving total mTSS (0 [normal] to 380 [maximal disease]).
Large positive change in mTSS indicates disease progression; small positive/no change indicates slowing/halting of disease progression.
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Baseline, Week 26
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Number of Participants Meeting ACR20 Response Criteria at Week 26 (ACR: American College of Rheumatology)
Délai: Week 26
|
Patients were ACR20 responders if they had: >= 20% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=20% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant C-reactive protein.
Patients who discontinued or switched to open-label adalimumab prior to Week 26 were considered non-responders.
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Week 26
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Number of Participants Meeting ACR50 Response Criteria at Week 26 (ACR: American College of Rheumatology)
Délai: Week 26
|
Patients were ACR50 responders if they had: >= 50% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=50% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant C-reactive protein.
Patients who discontinued or switched to open-label adalimumab prior to Week 26 were considered non-responders.
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Week 26
|
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Number of Participants Meeting ACR70 Response Criteria at Week 26 (ACR: American College of Rheumatology)
Délai: Week 26
|
Patients were ACR70 responders if they had: >= 70% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=70% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant C-reactive protein.
Patients who discontinued or switched to open-label adalimumab prior to Week 26 were considered non-responders.
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Week 26
|
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Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 26
Délai: Baseline, Week 26
|
Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis.
Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate.
DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity.
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Baseline, Week 26
|
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Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 26
Délai: Week 26
|
Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis.
Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate.
DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity.
DAS28(ESR) score <2.6 was defined as clinical remission of disease.
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Week 26
|
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Number of Participants Who Reported Any Adverse Event (Serious or Non-serious) on Double-blind Study Drug Through Week 26
Délai: Through Week 26
|
Adverse events were collected at designated study visits for all participants who were randomized and received at least 1 dose of study drug.
The number of participants who experienced any adverse event (serious or non-serious) while receiving double-blind study drug is summarized.
See the Reported Adverse Event section for details.
|
Through Week 26
|
|
Change From Baseline in Modified Total Sharp X-Ray Score at Week 52
Délai: Baseline, Week 52
|
Modified Total Sharp Score (mTSS) is a measure of joint health, used in evaluation of inhibition of radiographic progression of disease.
Digitized X-rays of hands and feet were obtained then scored in a blinded manner: for erosions (0 [no damage] to 5 [complete collapse or total destruction of joint]) and for joint space narrowing (0 [no damage] to 4 [complete luxation of joint]).
Scores were added, giving total mTSS score (0 [normal] to 380 [maximal disease]).
Large positive change in mTSS indicates diseae progression; small positive/no change indicates slowing/halting of disease progression.
|
Baseline, Week 52
|
|
Number of Participants Meeting ACR20 Response Criteria at Week 52 (ACR: American College of Rheumatology)
Délai: Week 52
|
Patients were ACR20 responders if they had: >=20% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=20% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire (HAQ); and acute phase reactant C-reactive protein.
|
Week 52
|
|
Number of Participants Meeting ACR50 Response Criteria at Week 52 (ACR: American College of Rheumatology)
Délai: Week 52
|
Patients were ACR50 responders if they had: >=50% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=50% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire (HAQ); and acute phase reactant C-reactive protein.
|
Week 52
|
|
Number of Participants Meeting ACR70 Response Criteria at Week 52 (ACR: American College of Rheumatology)
Délai: Week 52
|
Patients were ACR70 responders if they had: >=70% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus >=70% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire (HAQ); and acute phase reactant C-reactive protein.
|
Week 52
|
|
Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 52
Délai: Baseline, Week 52
|
Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis.
Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate.
DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity.
|
Baseline, Week 52
|
|
Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 52
Délai: Week 52
|
Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis.
Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate.
DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity.
DAS28(ESR) score <2.6 was defined as clinical remission of disease.
|
Week 52
|
|
Number of Participants Who Reported Any Adverse Event (Serious or Non-serious) While Receiving Adalimumab Through Week 52
Délai: Through Week 52
|
Adverse events were collected at designated study visits for all participants who were randomized and received at least 1 dose of adalimumab.
The number of participants who experienced any adverse event (serious or non-serious) while receiving any adalimumab during the study (double-blind adalimumab and/or open-label) is summarized.
See the Reported Adverse Event section for details.
|
Through Week 52
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Directeur d'études: Hiroshi Ukai, BS, Abbott Japan Co.,Ltd
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- Burmester GR, Landewe R, Genovese MC, Friedman AW, Pfeifer ND, Varothai NA, Lacerda AP. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2017 Feb;76(2):414-417. doi: 10.1136/annrheumdis-2016-209322. Epub 2016 Jun 23.
- Yamanaka H, Ishiguro N, Takeuchi T, Miyasaka N, Mukai M, Matsubara T, Uchida S, Akama H, Kupper H, Arora V, Tanaka Y. Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab to methotrexate-treated Japanese patients with early rheumatoid arthritis: 52-week results of the HOPEFUL-1 trial. Rheumatology (Oxford). 2014 May;53(5):904-13. doi: 10.1093/rheumatology/ket465. Epub 2014 Jan 17.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 mars 2009
Achèvement primaire (Réel)
1 mars 2011
Achèvement de l'étude (Réel)
1 août 2011
Dates d'inscription aux études
Première soumission
26 mars 2009
Première soumission répondant aux critères de contrôle qualité
26 mars 2009
Première publication (Estimation)
27 mars 2009
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
7 août 2012
Dernière mise à jour soumise répondant aux critères de contrôle qualité
1 août 2012
Dernière vérification
1 août 2012
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- M06-859
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .