Efficacy and Safety Study of Abatacept Subcutaneous Plus Methotrexate in Inducing Remission in Adults With Very Early Rheumatoid Arthritis
9. Dezember 2015 aktualisiert von: Bristol-Myers Squibb
A Phase 3b, Randomized, Active Controlled Trial to Evaluate the Efficacy and Safety of Abatacept SC in Combination With Methotrexate in Inducing Clinical Remission Compared to Methotrexate Monotherapy in Adults With Very Early RA
The primary purpose of the protocol is to demonstrate the ability of abatacept plus methotrexate to induce remission in patients with very early rheumatoid arthritis after 12 months of treatment and to maintain remission following 6 months of drug withdrawal.
Studienübersicht
Status
Abgeschlossen
Bedingungen
Intervention / Behandlung
Studientyp
Interventionell
Einschreibung (Tatsächlich)
511
Phase
- Phase 3
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
-
-
Queensland
-
Cairns, Queensland, Australien, 4870
- Local Institution
-
Maroochydore, Queensland, Australien, 4558
- Local Institution
-
-
South Australia
-
Woodville, South Australia, Australien, 5011
- Local Institution
-
-
Victoria
-
Heidelberg, Victoria, Australien, 3084
- Local Institution
-
Malvern, Victoria, Australien, 3144
- Local Institution
-
-
Western Australia
-
Victoria Park, Western Australia, Australien, 6100
- Local Institution
-
-
-
-
-
Bruxelles, Belgien, 1200
- Local Institution
-
Kortrijk, Belgien, 8500
- Local Institution
-
Merksem, Belgien, 2170
- Local Institution
-
-
-
-
-
Berlin, Deutschland, 10117
- Local Institution
-
Berlin, Deutschland, 14059
- Local Institution
-
Hildesheim, Deutschland, 31134
- Local Institution
-
Muenchen, Deutschland, 80336
- Local Institution
-
Muenchen, Deutschland, 80639
- Local Institution
-
Muenchen, Deutschland, 81541
- Local Institution
-
-
-
-
-
Hjorring, Dänemark, 9800
- Local Institution
-
-
-
-
-
Helsinki, Finnland, 00290
- Local Institution
-
Tampere, Finnland, 33521
- Local Institution
-
-
-
-
-
Chambray Les Tours, Frankreich, 37170
- Local Institution
-
Montpellier, Frankreich, 34295
- Local Institution
-
Paris Cedex 14, Frankreich, 75679
- Local Institution
-
Poitiers, Frankreich, 86021
- Local Institution
-
-
-
-
-
Ancona, Italien, 60055
- Local Institution
-
Siena, Italien, 53100
- Local Institution
-
-
-
-
Alberta
-
Calgary, Alberta, Kanada, T2N 4N1
- Local Institution
-
-
Quebec
-
Laval, Quebec, Kanada, H7T 2P5
- Local Institution
-
-
-
-
-
Daegu, Korea, Republik von, 705-718
- Local Institution
-
Daejeon, Korea, Republik von, 302-799
- Local Institution
-
Seoul, Korea, Republik von, 137-701
- Local Institution
-
Seoul, Korea, Republik von, 133-791
- Local Institution
-
-
-
-
-
Chihuahua, Mexiko, 31000
- Local Institution
-
Queretaro, Mexiko, 76178
- Local Institution
-
San Luis Potosi, Mexiko, 78240
- Local Institution
-
-
Estado De Mexico
-
Metepec, Estado De Mexico, Mexiko, 52140
- Local Institution
-
-
Jalisco
-
Guadalajara, Jalisco, Mexiko, 44500
- Local Institution
-
Guadalajara, Jalisco, Mexiko, 44690
- Local Institution
-
-
Nuevo Leon
-
Monterrey, Nuevo Leon, Mexiko, 64020
- Local Institution
-
-
Yucatan
-
Merida, Yucatan, Mexiko, 97000
- Local Institution
-
-
-
-
-
Lublin, Polen, 20-954
- Local Institution
-
Poznan, Polen, 60-218
- Local Institution
-
Torun, Polen, 87100
- Local Institution
-
Warszawa, Polen, 01-157
- Local Institution
-
Warszawa, Polen, 01-868
- Local Institution
-
Wroc#aw, Polen, 50-088
- Local Institution
-
-
-
-
-
Moscow, Russische Föderation, 117049
- Local Institution
-
Moscow, Russische Föderation, 129327
- Local Institution
-
Tver, Russische Föderation, 170036
- Local Institution
-
-
-
-
-
Goteborg, Schweden, 413 45
- Local Institution
-
Linkoping, Schweden, 581 85
- Local Institution
-
Malmo, Schweden, 205 02
- Local Institution
-
Stockholm, Schweden, 171 76
- Local Institution
-
Uppsala, Schweden, 751 85
- Local Institution
-
-
-
-
Gauteng
-
Kempton Park, Gauteng, Südafrika, 1619
- Local Institution
-
Pretoria, Gauteng, Südafrika, 0083
- Local Institution
-
Pretoria, Gauteng, Südafrika, 0084
- Local Institution
-
Pretoria, Gauteng, Südafrika, 0181
- Local Institution
-
-
Kwa Zulu Natal
-
Durban, Kwa Zulu Natal, Südafrika, 4001
- Local Institution
-
-
Western Cape
-
Panorama, Western Cape, Südafrika, 7500
- Local Institution
-
-
-
-
Alabama
-
Huntsville, Alabama, Vereinigte Staaten, 35801
- Rheumatology Associates Of North Alabama, P.C.
-
-
Arkansas
-
Hot Springs, Arkansas, Vereinigte Staaten, 71913
- St. Joseph'S Mercy Clinic
-
-
Florida
-
Sarasota, Florida, Vereinigte Staaten, 34239
- Sarasota Arthritis Research Center
-
-
Idaho
-
Coeur D Alene, Idaho, Vereinigte Staaten, 83814
- Coeur D'Alene Arthrit Clin
-
-
Maryland
-
Baltimore, Maryland, Vereinigte Staaten, 21224
- Johns Hopkins University Division of Rheumatology
-
-
Massachusetts
-
Worcester, Massachusetts, Vereinigte Staaten, 01605
- Clinical Pharmacology Study Group
-
-
Mississippi
-
Jackson, Mississippi, Vereinigte Staaten, 39202
- Arthritis Associates Of Mississippi
-
-
Nebraska
-
Lincoln, Nebraska, Vereinigte Staaten, 68516
- Physician Research Collaboration, LLC
-
-
North Carolina
-
Hickory, North Carolina, Vereinigte Staaten, 28602
- Piedmont Rheumatology, Pa
-
Wilmington, North Carolina, Vereinigte Staaten, 28401
- Carolina Arthritis Associates
-
-
Ohio
-
Cleveland, Ohio, Vereinigte Staaten, 44109
- MetroHealth Medical Center
-
Middleburg, Ohio, Vereinigte Staaten, 44130
- Isam A. Diab, Md
-
-
Pennsylvania
-
Duncansville, Pennsylvania, Vereinigte Staaten, 16635
- Alan J. Kivitz, Md, Cpi
-
-
South Carolina
-
Orangeburg, South Carolina, Vereinigte Staaten, 29118
- Mitchell C. Feinman, Md
-
-
Wisconsin
-
Glendale, Wisconsin, Vereinigte Staaten, 53217
- Kurt Oelke, Md
-
-
Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre und älter (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Beschreibung
Key Inclusion Criteria:
- Presence of active clinical synovitis in at least 2 joints, 1 of which must have been a small joint, for a minimum of 8 weeks prior to screening
- Onset of persistent symptoms ≤ 2 years prior to screening
- Positive test result for anticyclic citrullinated peptides 2
- Methotrexate naive or with minimum exposure to methotrexate, defined as no more than 10 mg/week for ≤4 weeks and no methotrexate dose for 1 month prior to screening visit
- Biologic naive, including no treatment with an investigational biologic prior to screening
- Disease Activity Score 28 based on C-reactive protein score ≥3.2 at screening
- Withdrawal from any treatment with chloroquine, hydroxychloroquine, and/or sulfasalazine (wash-out) for a minimum of 28 days prior to randomization
- If receiving oral corticosteroids, on a stable low dose (≤ 10 mg/day prednisone equivalent) for at least 4 weeks
- Able to undergo magnetic resonance imaging
Key Exclusion Criteria:
- Meeting diagnostic criteria for other rheumatic disease (eg, lupus erythematosus)
- Treatment with an intravenous, intramuscular, or intraarticular corticosteroid within 4 weeks prior to randomization
- Scheduled for or anticipating joint replacement surgery
- Presence of concomitant illness likely to require systemic glucocorticosteroid therapy during the study, in the opinion of the investigator
- History of malignancy in the last 5 years
- Any serious bacterial infection within the last 3 months not treated or resolved with antibiotics, or any chronic or recurrent bacterial infection
- At risk for tuberculosis
- Evidence of active or latent bacterial or viral infection at the time of potential enrollment, including human immunodeficiency or herpes zoster virus or cytomegalovirus that resolved less than 2 months prior to enrollment
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Doppelt
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Aktiver Komparator: Abatacept, 125 mg, plus methotrexate, 2.5 mg
Participants received abatacept, 125 mg subcutaneously, plus methotrexate, 2.5 mg orally as tablets, once weekly, during the 12-month Treatment Period
|
Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months
Andere Namen:
Tablets, oral, 2.5 mg, once weekly, 12 months
Andere Namen:
|
|
Aktiver Komparator: Methotrexate, 2.5 mg, plus abatacept placebo
Participants received methotrexate, 2.5 mg, orally as tablets, plus abatacept placebo subcutaneously, once weekly during the 12-month Treatment Period
|
Tablets, oral, 2.5 mg, once weekly, 12 months
Andere Namen:
Injection, subcutaneous, to match 125 mg by syringe, once weekly, 12 months
|
|
Aktiver Komparator: Abatacept, 125 mg, plus methotrexate placebo
Participants received abatacept, 125 mg subcutaneously, plus methotrexate placebo tablets orally, once weekly during the 12-month Treatment Period
|
Injection, subcutaneous, 125 mg by syringe, once weekly, 12 months
Andere Namen:
Tablets, oral, to match 2.5-mg tablet, once weekly, 12 months
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Percentage of Participants Who Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18
Zeitfenster: Randomization to Months 12 and 18
|
DAS28-CRP remission defined as <2.6;
TP=treatment phase; WP=withdrawal phase.
The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad).
These measures are then fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
|
Randomization to Months 12 and 18
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Percentage of Participants Who Received Monotherapy and Achieved Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria at Month 12 and at Both Months 12 and 18
Zeitfenster: Randomization to Months 12 and 18
|
TP=treatment period; WP=withdrawal period.
Remission defined as DAS28-CRP<2.6.
The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad).
DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity.
Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
|
Randomization to Months 12 and 18
|
|
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time - Intent to Treat Population
Zeitfenster: Randomization to Month 24
|
TP=treatment period; WP=withdrawal period.
Remission defined as DAS28-CRP<2.6.
The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad).
DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity.
Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
|
Randomization to Month 24
|
|
Adjusted Mean Change From Baseline in Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) at Months 6, 12, and 18
Zeitfenster: Baseline to Month 18
|
TP=treatment period; WP=withdrawal period.
The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) that assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad).
DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity.
Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.)
|
Baseline to Month 18
|
|
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) at Months 12 and 18
Zeitfenster: Randomization to Month 18
|
TP=treatment period; WP=withdrawal period.
SDAI-defined remission= ≤3.3.
The SDAI is the simple linear sum of 5 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) (based on a 28-joint assessment); patient's and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, on which higher scores=greater affection due to disease activity); and C-reactive protein level (mg/dL).
SDAI total score=0-86.
SDAI <=3.3 indicates disease remission, >3.4 to 11=low disease activity, >11 to 26=moderate disease activity, and >26=high disease activity.
TJC is assessed and recorded at each visit, with no swelling=0, swelling=1.
SJC is assessed through identification of joints that are painful under pressure or to passive motion.
TJC is recorded on the joint assessment form at each visit, with no tenderness =0, tenderness = 1.
Higher score indicates greater affection due to disease activity.
|
Randomization to Month 18
|
|
Adjusted Mean Change From Baseline in Scores on Simplified Disease Activity Index (SDAI) Over Time
Zeitfenster: Randomization to Month 18
|
TP=treatment period; WP=withdrawal period.
The SDAI is the simple linear sum of 5 outcome parameters: swollen joint count (SJC) and tender joint count (TJC) (based on a 28-joint assessment); patient's and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, on which higher scores=greater affection due to disease activity); and C-reactive protein level (mg/dL).
SDAI total score=0-86.
SJC is assessed and recorded at each visit, with no swelling=0, swelling=1 (higher score indicates greater swelling).
TJC is assessed at each visit through identification of joints that are painful under pressure or to passive motion, with no tenderness=0, tenderness=1 (higher score indicates greater affection due to disease activity)..
|
Randomization to Month 18
|
|
Percentage of Participants Achieving a Health Assessment Questionnaire (HAQ) Response Over Time
Zeitfenster: Randomization to Month 24
|
HAQ response defined as a reduction of at least 0.3 units from baseline in score on the Health Assessment Questionnaire Disability Index (HAQ-DI), which assesses patients' functional ability by rating their abilities over the previous week.
The HAQ-DI includes at least 2 questions from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities.
Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do.
The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3.
When aids, devices, or help is indicated by the patient, the score for the category item is raised from a 0 or a 1 to a 2, but if the patient's highest score for a subcategory is a 3, it stays a 3.
|
Randomization to Month 24
|
|
Adjusted Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Over Time
Zeitfenster: Randomization to Month 18
|
The Health Assessment Questionnaire Disability Index (HAQ-DI) assesses patients' functional ability by rating their abilities over the previous week.
The HAQ-DI includes at least 2 questions from each of 8 categories: dressing and grooming, hygiene, arising, reach, eating, grip, walking, and common daily activities.
Patients rate difficulty performing specific tasks: 0=without difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do.
The sum of the categories score (the highest scored item in the category) is divided by the number of categories answered, yielding a score from 0-3.
When aids, devices, or help is indicated by the patient, the score for the category item is raised from a 0 or a 1 to a 2, but if the patient's highest score for a subcategory is a 3, it stays a 3.
|
Randomization to Month 18
|
|
Adjusted Mean Change From Baseline at Months 6, 12, and 18 in Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of Short Form-36 (SF-36)
Zeitfenster: Randomization to Months 6, 12, and 18
|
TP=treatment period; WP=withdrawal period.
The SF-36 is a 36-item self-administered questionnaire developed to assess health-related quality of life (QOL) and comprises 8 domains, including 4 physical (physical health, bodily pain, physical functioning and physical role limitations) and 4 mental (mental health, vitality, social functioning, and emotional role limitation) subscales.
Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QOL (0=Poorest Health; 100=Best Health).
Mean change from baseline=postbaseline value-baseline value; a higher value signifies improvement.
|
Randomization to Months 6, 12, and 18
|
|
Adjusted Mean Change From Baseline Over Time in Findings on Magnetic Resonance Imaging (MRI)
Zeitfenster: Randomization to Month 18
|
TP=treatment period; WP=withdrawal period.
Change from Baseline=Postbaseline-baseline value.
MRI was used to assess joint damage progression at Months 6, 12, and 18.
If >20% of joints with a missing score for a parameter (erosion, osteitis, and synovitis), the MRI score of each parameter was considered missing.
If ≤20% of joints had a missing score for a parameter, the MRI score for that parameter from the missing joints was carried forward from the previous MRI assessment, or carried backward from the next MRI assessment, if missing score occurred at baseline.
MRI total score ranged from 0 (best outcome) to 4 (worst outcome).
A gadolinium-enhanced MRI of the dominant hand-wrist was performed on all randomized patients at 5 points.
The hand/wrist assessed to have more synovitis was selected initially and used for all subsequent evaluations.
The MRI examination was standardized to ensure sufficient image quality for the evaluation of radiographic progression of rheumatoid arthritis.
|
Randomization to Month 18
|
|
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Related Adverse Events (AEs), and Discontinuations Due to AEs During the Treatment Period
Zeitfenster: Day 1 to up to 56 days following the last dosing day (Day 365); all deaths during study period, including those that occurred >56 days after last dose in Treatment Period
|
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Related=having certain, probable, possible, or unknown relationship to study drug.
|
Day 1 to up to 56 days following the last dosing day (Day 365); all deaths during study period, including those that occurred >56 days after last dose in Treatment Period
|
|
Adverse Events (AEs) of Interest During the Treatment Period
Zeitfenster: Day 1 to 56 days following last dosing day (Day 365)
|
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Related=having certain, probable, possible, or unknown relationship to study drug.
AEs of special interest are events potentially associated with the drug or disease under study.
|
Day 1 to 56 days following last dosing day (Day 365)
|
|
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality During Treatment Period
Zeitfenster: Day 1 up to 56 days following the last dosing day in the Treatment Period (Day 365)
|
Lower limit of normal (LLN); Upper limit of normal (ULN); Pretreatment (preRX).
Criteria for marked abnormality: Platelet count (*10^9 c/µL) <0.67*LLN or >1.5*ULN, or if preRX<LLN, use 0.5*preRX and <100,000/mm^3; potassium, serum (mEq) <0.9*LLN or >1.1*ULN, or if preRX <LLN, use <0.9*preRX or >ULN if preRX>ULN, use >1.1*preRX or <LLN; blood urea nitrogen (mg/dL) >2*preRX; creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; AST (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; ALP (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; G-glutamyl transferase U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; uric acid (mg/dL)>1.5*ULN,
or if preRX, use >2*preRX; albumin (g/dL) <0.9*LLN, or if preRX<LLN, use <0.75*preRX; hemoglobin (g/dL)>3 decrease from preRX; hematocrit (%) < 0.75*preRX.
|
Day 1 up to 56 days following the last dosing day in the Treatment Period (Day 365)
|
|
Percentage of Participants With Remission by Disease Activity Score 28 Based on C-reactive Protein (DAS28-CRP) Criteria Over Time During Withdrawal Period- Treated Participants in Remission at Month 12
Zeitfenster: End of Treatment Period (Month 12) to End of Withdrawal Period (Month 24)
|
WP=withdrawal period.
Remission defined as DAS28-CRP<2.6.
The DAS 28-CRP is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad).
DAS-CRP scores range from 0 to 10, with higher values indicating greater disease activity.
Individual measures are fed into a complex mathematical formula to produce the overall DAS (a score greater than 5.1 implies active disease; less than 3.2, well controlled disease; and less than 2.6, remission.).
Percentage= number of participants with remission divided by number of participants who were analyzed (all treated participants who were in remission at end of treatment period and entered the Withdrawal Period)
|
End of Treatment Period (Month 12) to End of Withdrawal Period (Month 24)
|
|
Percentage of Participants Who Achieved Remission by Criteria of the Simplified Disease Activity Index (SDAI) Over Time in Treatment Period and Withdrawal Period
Zeitfenster: Randomization to Month 24
|
TP=treatment period; WP=withdrawal period.
SDAI-defined remission= ≤3.3.
The SDAI is the simple linear sum of 5 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) (based on a 28-joint assessment); patient's and physician's global assessments of disease activity (assessed on 0-10 cm visual analog scale, on which higher scores=greater affection due to disease activity); and C-reactive protein level (mg/dL).
SDAI total score=0-86.
SDAI <=3.3 indicates disease remission, >3.4 to 11=low disease activity, >11 to 26=moderate disease activity, and >26=high disease activity.
TJC is assessed and recorded at each visit, with no swelling=0, swelling=1.
SJC is assessed through identification of joints that are painful under pressure or to passive motion.
TJC is recorded on the joint assessment form at each visit, with no tenderness =0, tenderness = 1.
Higher score indicates greater affection due to disease activity.
Percent=number with remission/number evaluated (ITT)
|
Randomization to Month 24
|
|
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs) and Discontinuations Due to AEs During the Full Study (All Periods)
Zeitfenster: Day 1 to 56 days post last dose in the study, up to Month 30
|
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Includes data up to last active dose date +56 days if the participant discontinued the Treatment Period or did not enter the Withdrawal Period, up to the day of discontinuation in the Withdrawal Period for participants discontinuing the Withdrawal Period without entering the Re-exposure Period (RP), up to Day 729 visit (Month 24) for participants who complete the Withdrawal Period, and up to 56 days post last active dose in Re-exposure Period for participants entering the Re-exposure Period.
|
Day 1 to 56 days post last dose in the study, up to Month 30
|
|
Adverse Events (AEs) of Interest During the Withdrawal Period
Zeitfenster: Last dose in TP + 57 days, up to Month 24
|
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
AEs of special interest are events potentially associated with the drug or disease under study.
Includes events with an onset date on or after 57 days post last dosing day (active abatacept or active MTX whichever is the later) in the Treatment Period and up to end of Withdrawal Period.
Treatment groups represent treatment received during the Treatment Period.
|
Last dose in TP + 57 days, up to Month 24
|
|
Adverse Events (AEs) of Interest During the Re-exposure Period
Zeitfenster: First dose in Re-exposure period up to last dose of Re-exposure Period + 56 days
|
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
AEs of special interest are events potentially associated with the drug or disease under study.
Includes data up to 56 days post the last dosing day (active abatacept or active MTX, whichever is the later) in the Re-exposure Period.
Treatment groups represent Treatment received during Treatment Period.
|
First dose in Re-exposure period up to last dose of Re-exposure Period + 56 days
|
|
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Withdrawal Period
Zeitfenster: Last dose in TP + 57 days, up to Month 24
|
LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment.
Criteria for marked abnormality on laboratory test results: Platelet count (*10^9 c/µL) <0.67*LLN or >1.5*ULN, or if preRX<LLN, use 0.5*preRX and <100,000/mm^3; potassium, serum (mEq) <0.9*LLN or >1.1*ULN, or if preRX <LLN, use <0.9*preRX or >ULN if preRX>ULN, use >1.1*preRX or <LLN; blood urea nitrogen (mg/dL) >2*preRX; creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; AST (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; ALP (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; G-glutamyl transferase (GGT) (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; uric acid (mg/dL)>1.5*ULN,
or if preRX, use >2*preRX; albumin (g/dL) <0.9*LLN, or if preRX<LLN, use <0.75*preRX; hemoglobin (g/dL)>3 decrease from preRX; hematocrit (%) < 0.75*preRX.
|
Last dose in TP + 57 days, up to Month 24
|
|
Number of Participants With Results on Hematology and Clinical Laboratory Tests Meeting the Criteria for Marked Abnormality in Re-exposure Period
Zeitfenster: Start of re-exposure period to 56 days post last dose, up to Month 30
|
LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment.
Criteria for marked abnormality on laboratory test results: Platelet count (*10^9 c/µL) <0.67*LLN or >1.5*ULN, or if preRX<LLN, use 0.5*preRX and <100,000/mm^3; potassium, serum (mEq) <0.9*LLN or >1.1*ULN, or if preRX <LLN, use <0.9*preRX or >ULN if preRX>ULN, use >1.1*preRX or <LLN; blood urea nitrogen (mg/dL) >2*preRX; creatinine (mg/dL) >1.5*preRX; ALT (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; AST (U/L) >3*ULN, or if preRX>ULN, use >4*preRX; ALP (U/L) >2*ULN, or if preRX>ULN, use >3*preRX; G-glutamyl transferase U/L) >2*ULN, or if preRX>ULN, use >3*preRX; glucose, fasting (mg/dL) <0.8*LLN or >1.5*ULN, or if preRX<LLN use <0.8*preRX or >ULN if preRX >ULN, use >2.0*preRX or OR <LLN; glucose, serum (mg/dL) <65 or >220; uric acid (mg/dL)>1.5*ULN,
or if preRX, use >2*preRX; albumin (g/dL) <0.9*LLN, or if preRX<LLN, use <0.75*preRX; hemoglobin (g/dL)>3 decrease from preRX; hematocrit (%) < 0.75*preRX.
|
Start of re-exposure period to 56 days post last dose, up to Month 30
|
Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Publikationen und hilfreiche Links
Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.
Allgemeine Veröffentlichungen
- Ahmad HA, Baker JF, Conaghan PG, Emery P, Huizinga TWJ, Elbez Y, Banerjee S, Østergaard M. Prediction of flare following remission and treatment withdrawal in early rheumatoid arthritis: post hoc analysis of a phase IIIb trial with abatacept. Arthritis Res Ther. 2022 Feb 16;24(1):47. doi: 10.1186/s13075-022-02735-8.
- Keystone EC, Ahmad HA, Yazici Y, Bergman MJ. Disease activity measures at baseline predict structural damage progression: data from the randomized, controlled AMPLE and AVERT trials. Rheumatology (Oxford). 2020 Aug 1;59(8):2090-2098. doi: 10.1093/rheumatology/kez455.
- Ahmad HA, Baker JF, Ostergaard M, Ye J, Emery P, Conaghan PG. Determining MRI Inflammation Targets When Considering a Rheumatoid Arthritis Treat-to-Target Strategy: Results of a Randomized, Placebo-Controlled Trial. Adv Ther. 2019 Sep;36(9):2384-2393. doi: 10.1007/s12325-019-01020-6. Epub 2019 Jul 5.
- Emery P, Burmester GR, Bykerk VP, Combe BG, Furst DE, Maldonado MA, Huizinga TW. Re-treatment with abatacept plus methotrexate for disease flare after complete treatment withdrawal in patients with early rheumatoid arthritis: 2-year results from the AVERT study. RMD Open. 2019 Feb 8;5(1):e000840. doi: 10.1136/rmdopen-2018-000840. eCollection 2019.
- Bykerk VP, Burmester GR, Combe BG, Furst DE, Huizinga TWJ, Ahmad HA, Emery P. On-drug and drug-free remission by baseline symptom duration: abatacept with methotrexate in patients with early rheumatoid arthritis. Rheumatol Int. 2018 Dec;38(12):2225-2231. doi: 10.1007/s00296-018-4173-3. Epub 2018 Oct 20. Erratum In: Rheumatol Int. 2019 Feb 5;:
- Peterfy C, Burmester GR, Bykerk VP, Combe BG, DiCarlo JC, Furst DE, Huizinga TW, Wong DA, Conaghan PG, Emery P. Sustained improvements in MRI outcomes with abatacept following the withdrawal of all treatments in patients with early, progressive rheumatoid arthritis. Ann Rheum Dis. 2016 Aug;75(8):1501-5. doi: 10.1136/annrheumdis-2015-208258. Epub 2016 Feb 10.
- Emery P, Burmester GR, Bykerk VP, Combe BG, Furst DE, Barre E, Karyekar CS, Wong DA, Huizinga TW. Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24 months, with a 12-month, double-blind treatment period. Ann Rheum Dis. 2015 Jan;74(1):19-26. doi: 10.1136/annrheumdis-2014-206106. Epub 2014 Nov 3.
Nützliche Links
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn
1. Dezember 2010
Primärer Abschluss (Tatsächlich)
1. September 2013
Studienabschluss (Tatsächlich)
1. Oktober 2014
Studienanmeldedaten
Zuerst eingereicht
3. Juni 2010
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
10. Juni 2010
Zuerst gepostet (Schätzen)
11. Juni 2010
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
14. Januar 2016
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
9. Dezember 2015
Zuletzt verifiziert
1. Dezember 2015
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen des Immunsystems
- Autoimmunerkrankungen
- Gelenkerkrankungen
- Erkrankungen des Bewegungsapparates
- Rheumatische Erkrankungen
- Bindegewebserkrankungen
- Arthritis
- Arthritis, Rheuma
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Inhibitoren der Nukleinsäuresynthese
- Enzym-Inhibitoren
- Antirheumatika
- Antimetaboliten, antineoplastisch
- Antimetaboliten
- Antineoplastische Mittel
- Immunsuppressive Mittel
- Immunologische Faktoren
- Dermatologische Wirkstoffe
- Immun-Checkpoint-Inhibitoren
- Reproduktionskontrollmittel
- Abtreibungsmittel, nichtsteroidal
- Abtreibungsmittel
- Folsäure-Antagonisten
- Methotrexat
- Abatacept
Andere Studien-ID-Nummern
- IM101-226
- 2010-018674-20 (EudraCT-Nummer)
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .