- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT01313520
A Study to Evaluate the Effectiveness of Infliximab and Changes in Hand and Wrist Magnetic Resonance Imaging (MRI) in Participants With Active Rheumatoid Arthritis (RA) (P08136)
A Randomized Clinical Trial to Study the Effects of Infliximab on Clinical Efficacy and Hand and Wrist Magnetic Resonance Imaging (MRI) in Patients With Active Rheumatoid Arthritis (RA)(Protocol No. P08136)
Studieöversikt
Status
Betingelser
Intervention / Behandling
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 2
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
- Must have a clinical diagnosis of rheumatoid arthritis for at least 6 months
- Must have at least 6 tender joints AND 6 swollen joints
- Has a C-reactive protein ≥ 1.0 mg/L OR Erythrocyte Sedimentation Rate (ESR) ≥ 28 mm/hr
- Baseline MRI must show evidence of synovitis in the wrist
- Must have screening laboratory tests within acceptable levels
- Women of childbearing potential and all men must agree to use a medically accepted method of contraception prior to entering the study and continue throughout study up to 6 weeks after study completion
- Must meet tuberculosis (TB) screening criteria
- Have received methotrexate therapy for ≥ 3 months; dose must be stable for at least 8 weeks
- If taking the a disease modifying anti-rheumatic drug (DMARD) in combination with methotrexate must be on a stable dose
- Must have a clinically acceptable 12 lead electrocardiogram (ECG)
- If taking oral corticosteroids must be on a stable dose equivalent to ≤10 mg of prednisone (or prednisolone) per day for ≥2 weeks
- If taking daily non-steroidal anti-inflammatory drug (NSAID) must be on a stable dose for ≥2 weeks; if taking NSAID on an as-needed basis must agree to discontinue use for at least 3 days and use only acetaminophen for breakthrough pain for 3 days before each MRI and clinic visit
- If received biological therapies, the last dose of these drugs was to be received ≥ 3 months prior to the baseline visit AND the reason for discontinuations was not for safety considerations OR lack of efficacy
Exclusion Criteria:
- Are pregnant, intend to become pregnant, or are breastfeeding
- Has inflammatory arthritis other than RA
- Has uncontrolled hypertension
- Has moderate or severe congestive heart failure
- Has a history of or current signs and/or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, cerebral, or psychiatric disease
- Has a history of demyelinating disease or symptoms suggestive of multiple sclerosis or optic neuritis
- Is currently participating in another clinical study or have participated in a clinical study (e.g., laboratory or clinical evaluation) within 4 weeks
- Has history of any tumor with the exception of adequately treated basal cell carcinoma or carcinoma in situ of the cervix
- Has a history of any latent or active granulomatous infection including histoplasmosis, or coccidiomycosis
- Had a non-tuberculous mycobacterial infection or opportunistic infection (e.g. cytomegalovirus, Pneumocystis carinii, aspergillosis) within 6 months
- Has a history of an infected joint prosthesis which has not been removed or replaced
- Has a known hypersensitivity to human immunoglobulin proteins or other components of infliximab
- Has received rituximab or natalizumab
- Has known claustrophobia or other contraindication to MRI
- Does not meet washout period guidelines for previous treatments/injections/vaccinations
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Trippel
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Experimentell: Infliximab
3 mg/kg of Infliximab intravenous infusion
|
3 mg/kg of Infliximab at Weeks 0, 2, 6, 14 via intravenous infusion
Andra namn:
|
Placebo-jämförare: Placebo
saline via intravenous infusion
|
250 mL of 0.9% sodium chloride at Weeks 0, 2, 6, 14 via intravenous infusion
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Change From Baseline in the Volume Transfer Rate From the Blood Plasma to the Enhancing Synovium (Ktrans)
Tidsram: Baseline and week 14
|
Dynamic Contrast Enhanced (DCE) Magnetic Resonance Imaging (MRI) was performed on one hand at baseline, and then at treatment week 14 to measure the rate constant of transfer of contrast (Ktrans).
|
Baseline and week 14
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Percentage of Responders With a 20% Improvement From Baseline in American College of Rheumatology (ACR) Responder Criteria for Tender and Swollen Joints (ACR20).
Tidsram: Baseline and week 14
|
ACR20 requires that both tender and swollen joint counts improve by at least 20% from baseline, as well as a 20% improvement in at least 3 other core measures from the following: pain, patient's and physician's global assessment, physical disability and C-reactive protein (CRP).
|
Baseline and week 14
|
Percentage of Responders With a 50% Improvement From Baseline in American College of Rheumatology (ACR) Responder Criteria for Tender and Swollen Joints (ACR50).
Tidsram: Baseline and week 14
|
ACR50 requires that both tender and swollen joint counts improve by at least 50% from baseline, as well as a 50% improvement in at least 3 other core measures from the following: pain, patient's and physician's global assessment, physical disability and CRP.
|
Baseline and week 14
|
Change From Baseline in Standardized Z-scores of Composite Endpoint Consisting of Clinical Disease Activity Measure DAS28 CRP + Ktrans.
Tidsram: Baseline and Week 14
|
Clinical disease activity score (DAS28 CRP) is a composite index of the following: number of tender joints (28 joint count), number of swollen joints (28 joint count), Patient Global Assessment of Disease Status (GADP) on a 100 mm visual analog scale (VAS) and concentration of CRP.
Ktrans is the volume transfer rate from the blood plasma to the enhancing synovium.
The individual endpoints are standardized using z-scores, then the z-scores are averaged to create a composite endpoint by use of O'Brien's global statistic.
|
Baseline and Week 14
|
Change From Baseline in Standardized Z-scores of Composite Endpoint Consisting of Clinical Disease Activity Measure DAS28 CRP + Rheumatoid Arthritis MRI Score (RAMRIS) Synovitis + RAMRIS Osteitis.
Tidsram: Baseline and Week 14
|
DAS28 CRP is a composite index of the following: number of tender joints (28 joint count), number of swollen joints (28 joint count), GADP on a 100 mm VAS and concentration of CRP. RAMRIS Synovitis is an ordinal scoring system of hand synovitis that is scored from 0 to 3 in 8 locations, ranging from 0 to 24 total. RAMRIS Osteitis is an ordinal scoring system of hand osteitis that is scored from 0 to 3 in 25 locations, ranging from 0 to 75 total. The individual endpoints are standardized using z-scores, then the z-scores are averaged to create a composite endpoint by use of O'Brien's global statistic. |
Baseline and Week 14
|
Andra resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Change From Baseline in DAS28 CRP.
Tidsram: Baseline and Week 14
|
DAS28 CRP is a composite index of the following: number of tender joints (28 joint count), number of swollen joints (28 joint count), GADP on a 100 mm VAS and concentration of serum CRP.
Scores can range from 2-10; with higher values corresponding to higher disease activity, and lower values to better outcomes.
|
Baseline and Week 14
|
Change From Baseline in RAMRIS Synovitis.
Tidsram: Baseline and Week 14
|
RAMRIS Synovitis is an ordinal scoring system of hand synovitis that is scored from 0 to 3 in 8 locations.
The scores can range from 0 to 24, with higher values corresponding to higher disease activity, and lower values to better outcomes.
|
Baseline and Week 14
|
Change From Baseline in RAMRIS Osteitis.
Tidsram: Baseline and Week 14
|
RAMRIS Osteitis is an ordinal scoring system of hand osteitis that is scored from 0 to 3 in 25 locations.
The scores can range from 0 to 75, with higher values corresponding to higher disease activity, and lower values to better outcomes.
|
Baseline and Week 14
|
Samarbetspartners och utredare
Sponsor
Publikationer och användbara länkar
Allmänna publikationer
- Beals C, Baumgartner R, Peterfy C, Balanescu A, Mirea G, Harabagiu A, Popa S, Cheng A, Feng D, Ashton E, DiCarlo J, Vallee MH, Dardzinski BJ. Magnetic resonance imaging of the hand and wrist in a randomized, double-blind, multicenter, placebo-controlled trial of infliximab for rheumatoid arthritis: Comparison of dynamic contrast enhanced assessments with semi-quantitative scoring. PLoS One. 2017 Dec 13;12(12):e0187397. doi: 10.1371/journal.pone.0187397. eCollection 2017.
- MacIsaac KD, Baumgartner R, Kang J, Loboda A, Peterfy C, DiCarlo J, Riek J, Beals C. Pre-treatment whole blood gene expression is associated with 14-week response assessed by dynamic contrast enhanced magnetic resonance imaging in infliximab-treated rheumatoid arthritis patients. PLoS One. 2014 Dec 12;9(12):e113937. doi: 10.1371/journal.pone.0113937. eCollection 2014.
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- P08136
- 2011-000079-14 (EudraCT-nummer)
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
IPD-planbeskrivning
http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf
http://engagezone.msd.com/ds_documentation.php
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