- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT00502853
A Pilot Study of MabThera (Rituximab) Evaluated by MRI in Patients With Rheumatoid Arthritis.
7 luglio 2017 aggiornato da: Hoffmann-La Roche
Pilot Study to Evaluate the Effect of Mabthera in Combination With MTX in the Inhibition of Progression of Synovitis, Bone Marrow Edema, and Erosions Evaluated by Magnetic Resonance Imaging (MRI) in the Hand of Patients With Rheumatoid Arthritis.
This single arm study will measure the effect of MabThera in combination with methotrexate on the progression of synovitis, the extent of bone marrow edema, and the number of erosions in the wrist and hand of patients with rheumatoid arthritis, using a new MRI technique.
Patients will receive MabThera 1000mg i.v. on days 1 and 15, in combination with a stable dosage of 10-25mg/week methotrexate throughout the duration of the study.
Further courses of MabThera will be provided to eligible patients.
MRI will be performed 1-2 weeks before treatment initiation, and repeated 1 and 6 months after the first MabThera infusion.
The anticipated time on study treatment is 1-2 years, and the target sample size is <100 individuals.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Tipo di studio
Interventistico
Iscrizione (Effettivo)
10
Fase
- Fase 4
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Liguria
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Genova, Liguria, Italia, 16132
- Università Degli Studi Di Genova - Dimi; Reumatologia
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
Da 18 anni a 75 anni (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
Inclusion Criteria:
- adult patients, 18-75 years of age;
- rheumatoid arthritis for >=3 months and <=10 years;
- inadequate response to methotrexate (12.5-25mg/week) for >=3 months;
- evidence of erosive disease and/or clinical synovitis in a signal joint.
Exclusion Criteria:
- autoimmune rheumatic diseases other than RA;
- surgical operations on bones/joints in 12 weeks prior to baseline visit;
- concomitant treatment with biologic agents;
- previous treatment with more than one biologic agent approved for RA, or with cell-depleting therapies.
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: 1
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1000 mg iv nei giorni 1 e 15
10-25 mg/settimana
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Synovitis Score
Lasso di tempo: Baseline, Week 4, and Week 24
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Extension and degree of synovitis in wrist according to RAMRIS score developed by OMERACT.
Synovitis is an area in synovial compartment that shows above normal post-gadolinium enhancement of a thickness greater than width of normal synovium.
Synovitis is assessed in 3 wrist regions (distal radioulnar joint; radiocarpal joint; intercarpal and carpometacarpal joints) and in each metacarpophalangeal (MCP) joint.
1st carpometacarpal joint and 1st MCP joint are not scored.
Score 0 is normal, and 1-3 (mild, moderate, severe) are by thirds of the presumed maximum volume of enhancing tissue in the synovial compartment.
Total synovitis score=the sum of the individual scores (3 wrist regions [range 0-9] or 4 MCP joints [range 0-12]) for an overall range of 0-21, where 0=no damage and maximum score [9, 12, or 21]=most severe damage.
Change in synovitis = Follow-up synovitis score - baseline score.
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Baseline, Week 4, and Week 24
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OMERACT RAMRIS Bone Edema Score
Lasso di tempo: Baseline, Weeks 4 and 24
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Extension and degree of bone edema in the wrist according to the RAMRIS score developed by OMERACT.
Bone edema is a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content.
Each bone (wrists: carpal bones, distal radius, distal ulna, metacarpal bases; MCP joints: metacarpal heads, phalangeal bases) is scored separately.
The scale of 0-3 was based on the proportion of bone with edema, as follows: 0=no edema; 1=1 percent (%) to 33% of bone was edematous; 2 = 34%-66% of bone was edematous; and 3= 67%-100% of bone was edematous.
Total bone edema score=sum of the individual scores for an overall range of 0-69, where 0=no edema and 69=most severe edema.
Change in bone edema = follow-up bone edema score - baseline score.
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Baseline, Weeks 4 and 24
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OMERACT RAMRIS Erosion Score
Lasso di tempo: Baseline, Week 4, and Week 24
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MRI bone erosion measures a sharply marginated bone lesion, with correct juxta-articular localization and typical signal characteristics, which is visible in 2 planes with a cortical break seen in at least 1 plane.
Each bone (wrists: carpal bones, distal radius, distal ulna, metacarpal bases; MCP joints: metacarpal heads, phalangeal bases) scored separately.
Scale is 0-10 based on proportion of eroded bone compared to assessed bone volume (0=no erosion; 1=1%-10% of bone eroded; 2=11%-20%, etc).
For long bones, assessed bone volume is from articular surface (or best estimated position if absent) to depth of 1 centimeter (cm); in carpal bones it is the whole bone.
Total erosion score=sum of individual scores for an overall range of 0-230, where 0=no erosion and 230=most severe erosion.
Change in erosion=Follow-up erosion score - baseline score.
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Baseline, Week 4, and Week 24
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Early Enhancement Rate (REE)
Lasso di tempo: Baseline, Weeks 4 and 24
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A low cost, low field dedicated extremity MRI unit was used, which is specifically designed for the examination of peripheral joints.
In addition to the standard OMERACT-RAMRIS scoring system, additional data were elaborated by using "dynamic" MRI, i.e.
Contrast-Enhanced Dynamic MRI (DCE-MRI).
This method evaluates the diffusion of the contrast mean in a series of very short sequences thus providing a diffusion curve which is proportionate to the extent of inflammation in the synovial membrane.
Numerical parameters used with this method are the slope in the initial phase (rate of early enhancement - REE) and its "steady state" condition (relative enhancement - RE). REE per second during the first 55 seconds was calculated according to the formula REE55 = (S55-S0)/(S0x55)x100%.
The REE shows the slope of the curve of contrast uptake tangential to the α angle and is steeper if inflammation is higher.
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Baseline, Weeks 4 and 24
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Relative Enhancement (RE) Score
Lasso di tempo: Baseline, Weeks 4 and 24
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A low cost, low field dedicated extremity MRI unit was used, which is specifically designed for the examination of peripheral joints.
In addition to the standard OMERACT-RAMRIS scoring system, additional data were elaborated by using "dynamic" MRI (DCE-MRI).
This method evaluates the diffusion of the contrast mean in a series of very short sequences thus providing a diffusion curve which is proportionate to the extent of inflammation in the synovial membrane.
Numerical parameters used with this method are the slope in the initial phase (REE) and its "steady state" condition (RE).
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Baseline, Weeks 4 and 24
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Ritchie Articular Index Scores
Lasso di tempo: Baseline and Weeks 4, 12, and 24
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The Ritchie Articular Index is a graded assessment of tenderness in 26 joint regions.
The sum of the grades of tenderness (0=not tender, 1=tender, 2=tender and causes wince, and 3 tender, causes wince and effort to withdraw) elicited by applying firm pressure over the joint margin of articular joints (such as shoulders, elbow, wrists, hips).
The scores ranged from 0 (no tenderness) to 78 (most severe tenderness).
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Baseline and Weeks 4, 12, and 24
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Health Assessment Questionnaire - Disability Index (HAQ-DI) Score
Lasso di tempo: Baseline and Weeks 4, 12, and 24
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The Stanford HAQ-DI is a participant-reported questionnaire specific for rheumatoid arthritis (RA).
It consist of 20 items referring to eight component sets: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities.
Each item within a domain was scored on a 4-point Likert scale from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do.
The highest score reported by the participant for a domain determined the score for that domain.
The overall disability index is computed as the sum of domain scores and divided by the number of domains answered.
Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
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Baseline and Weeks 4, 12, and 24
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Patient's Global Assessment of Pain
Lasso di tempo: Baseline and Weeks 4, 12, and 24
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The participant's assessment of their current level of pain on a 0 to 100 millimeter (mm) horizontal VAS.
The left-hand extreme of the line was described as "no pain" and the right-hand as "unbearable pain".
The participant was asked to mark the line corresponding to their current level of pain and the distance from the left edge was recorded.
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Baseline and Weeks 4, 12, and 24
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DAS28 Score
Lasso di tempo: Baseline and Weeks 4, 12, and 24
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DAS28 calculated from the number of swollen joints and tender joints using the 28-joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and Patient's Global Assessment of Disease Activity (participant-rated arthritis activity assessment) with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity.
A DAS28 score of less than or equal to (≤) 3.2 = low disease activity, a DAS28 score of >3.2 to 5.1 = moderate to high disease activity.
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Baseline and Weeks 4, 12, and 24
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Erythrocyte Sedimentation Rate (ESR)
Lasso di tempo: Baseline and Weeks 4, 12, and 24
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ESR was determined using the Westergren method.
ESR measures how fast red blood cells (erythrocytes) fall to the bottom of a fine glass tube that is filled with the participant's blood.
The higher the sedimentation rate the greater the inflammation.
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Baseline and Weeks 4, 12, and 24
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C-Reactive Protein (CRP)
Lasso di tempo: Baseline and Weeks 4, 12, and 24
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CRP measured by milligrams per deciliter (mg/dL).
High levels of CRP are indicators of active inflammation.
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Baseline and Weeks 4, 12, and 24
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Anti-Cyclic Citrullinated Peptide (Anti-CCP) Autoantibodies Count
Lasso di tempo: Baseline and Weeks 4, 12, and 24
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Anti-CCP autoantibodies count measured by units per milliliter (U/mL).
The anti-CCP autoantibodies bind antigenic determinants that contain the unusual amino acid citrulline.
The anti-CCP antibody is a highly specific diagnostic test of RA (though with variable sensitivity) and a marker of joint damage with high prognostic significance.
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Baseline and Weeks 4, 12, and 24
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Rheumatoid Factor (RF) Immunoglobulin M (IgM) Concentrations
Lasso di tempo: Baseline and Weeks 4, 12, and 24
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RF IgM concentrations measured by international units per milliliter (IU/mL).
RF is an antibody reacting against the fragment, crystallizable (Fc) region of IgG.
Quantitative measurements have shown a prognostic value in distinguishing between progressive and non-progressive disease in early RA, a correlation with radiologically determined joint damage, and relation with clinical improvement after disease-modifying anti-rheumatic treatment.
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Baseline and Weeks 4, 12, and 24
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Total Immunoglobulin (Ig) Concentrations
Lasso di tempo: Baseline and Weeks 4, 12, and 24
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Total Ig concentrations as measured by milligrams per milliliter (mg/mL).
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Baseline and Weeks 4, 12, and 24
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Hematocrit Concentration (%)
Lasso di tempo: Baseline and Weeks 4, 12, and 24
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Baseline and Weeks 4, 12, and 24
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Percentage of Total B-lymphocytes
Lasso di tempo: Baseline and Weeks 4, 12, and 24
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Concentration of all B-lymphocytes subtypes was assessed.
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Baseline and Weeks 4, 12, and 24
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Erosion Score - Right Hand
Lasso di tempo: Baseline and Week 24
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The erosion score per joint of the hands can range from 0 to 5. Erosions were scored 1 if they were discrete but clearly present, and 2 or 3 if they were larger, depending on the surface area of the joint involved.
A score of 3 was given if the erosion was large and extended over the imaginary middle of the bone.
A score of 5 was given if a complete collapse of the joint was present or if the full surface of the joint was affected.
In each joint, individual erosions were summed up to a maximum of 5.
The maximal erosion score for each hand was thus 80, considering the 16 areas for erosions per hand.
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Baseline and Week 24
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Erosion Score - Left Hand
Lasso di tempo: Baseline and Week 24
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The erosion score per joint of the hands can range from 0 to 5. Erosions were scored 1 if they were discrete but clearly present, and 2 or 3 if they were larger, depending on the surface area of the joint involved.
A score of 3 was given if the erosion was large and extended over the imaginary middle of the bone.
A score of 5 was given if a complete collapse of the joint was present or if the full surface of the joint was affected.
In each joint, individual erosions were summed up to a maximum of 5.
The maximal erosion score for each hand was thus 80, considering the 16 areas for erosions per hand.
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Baseline and Week 24
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Joint Space Narrowing - Right Hand
Lasso di tempo: Baseline and Week 24
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Joint space narrowing and joint subluxation or luxation are combined in a single score with a range of 0 to 4. A normal joint space was scored 0. A score of 2 was allowed to a focal narrowing of the joint or to a joint space not sufficiently narrowed to be scored 2. The score of 1 was not to be used when the reader was unsure whether there was joint space narrowing.
A generalized narrowing leaving more than 50% of the original joint space present was scored 2. A generalized narrowing leaving less than 50% of the original joint space present was scored 3, and a subluxation of a joint was also scored 3. A bony ankylosis or a complete luxation of the joint was scored 4. A total of 13 joints were evaluated for narrowing and the scores were summed (13 times [x] 4 [maximum per joint]).
Each sum was normalized to a scale of 0 (best possible outcome) to 100 (worst possible outcome).
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Baseline and Week 24
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Joint Space Narrowing - Left Hand
Lasso di tempo: Baseline and Week 24
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Joint space narrowing and joint subluxation or luxation are combined in a single score with a range of 0 to 4. A normal joint space was scored 0. A score of 2 was allowed to a focal narrowing of the joint or to a joint space not sufficiently narrowed to be scored 2. The score of 1 was not to be used when the reader was unsure whether there was joint space narrowing.
A generalized narrowing leaving more than 50% of the original joint space present was scored 2. A generalized narrowing leaving less than 50% of the original joint space present was scored 3, and a subluxation of a joint was also scored 3. A bony ankylosis or a complete luxation of the joint was scored 4. A total of 13 joints were evaluated for narrowing and the scores were summed (13 x 4 [maximum per joint]).
Each sum was normalized to a scale of 0 (best possible outcome) to 100 (worst possible outcome).
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Baseline and Week 24
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X-Rays: Right Hand Total Score
Lasso di tempo: Baseline and Week 24
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Right hand total scores as measured by X-rays examining erosion and joint space narrowing.
Total score was calculated as the sum of the erosion score and the joint space narrowing score and scores ranged from 0 (best possible outcome) to 180 (worst possible outcome).
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Baseline and Week 24
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X-Rays: Left Hand Total Score
Lasso di tempo: Baseline and Week 24
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Left hand total scores as measured by X-rays examining erosion and joint space narrowing.
Total score was calculated as the sum of the erosion score and the joint space narrowing score and ranged from 0 (best possible outcome) to 180 (worst possible outcome).
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Baseline and Week 24
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio (Effettivo)
25 ottobre 2007
Completamento primario (Effettivo)
23 luglio 2010
Completamento dello studio (Effettivo)
23 luglio 2010
Date di iscrizione allo studio
Primo inviato
17 luglio 2007
Primo inviato che soddisfa i criteri di controllo qualità
17 luglio 2007
Primo Inserito (Stima)
18 luglio 2007
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
16 agosto 2017
Ultimo aggiornamento inviato che soddisfa i criteri QC
7 luglio 2017
Ultimo verificato
1 giugno 2017
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Malattie del sistema immunitario
- Malattie autoimmuni
- Malattie articolari
- Malattie muscoloscheletriche
- Malattie reumatiche
- Malattie del tessuto connettivo
- Artrite
- Artrite, reumatoide
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Inibitori della sintesi degli acidi nucleici
- Inibitori enzimatici
- Agenti antireumatici
- Antimetaboliti, Antineoplastici
- Antimetaboliti
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Agenti antineoplastici, immunologici
- Agenti dermatologici
- Agenti di controllo riproduttivo
- Agenti abortivi, non steroidei
- Agenti abortivi
- Antagonisti dell'acido folico
- Rituximab
- Metotrexato
Altri numeri di identificazione dello studio
- ML21081
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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