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Rituximab for the Treatment of Early Rheumatoid Arthritis (RA)

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ClinicalTrials.gov Identifier: NCT00396812
Recruitment Status : Terminated (The perceived risk-benefit ratio for individuals with early active RA)
First Posted : November 8, 2006
Results First Posted : November 14, 2012
Last Update Posted : February 12, 2013
Sponsor:
Collaborator:
Autoimmunity Centers of Excellence
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Intervention Drug: Rituximab
Enrollment 4
Recruitment Details 10 subjects were to be enrolled into the open label early Rheumatoid Arthritis trial at one site in the US. Enrollment occurred in 2008 but the study was terminated early due to Genentech’s announcement regarding rituximab’s risk-benefit ratio for individuals with early active Rheumatoid Arthritis.
Pre-assignment Details  
Arm/Group Title Rituximab
Hide Arm/Group Description

Participants to receive an intravenous infusion of rituximab (1 gram ) fourteen days apart, at baseline (Day 0) and at Week 2.

Concomitant treatments to be administered at a dose and frequency prescribed per protocol include methotrexate (MTX) and folic or folinic acid.

Period Title: Overall Study
Started 4
Completed 3 [1]
Not Completed 1
Reason Not Completed
Physician Decision             1
[1]
4 subjects completed treatment, but 1 subject terminated early due to disease progression
Arm/Group Title Rituximab
Hide Arm/Group Description

Participants to receive an intravenous infusion of rituximab (1 gram ) fourteen days apart, at baseline (Day 0) and at Week 2.

Concomitant treatments to be administered at a dose and frequency prescribed per protocol include methotrexate (MTX) and folic or folinic acid.

Overall Number of Baseline Participants 4
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants
<=18 years
0
   0.0%
Between 18 and 65 years
4
 100.0%
>=65 years
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants
43.3  (15.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants
Female
0
   0.0%
Male
4
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 4 participants
4
Disease Activity Score 28 -Erythrocyte Sedimentation Rate (DAS28-ESR)   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 4 participants
5.1  (1.3)
[1]
Measure Description: The DAS28-ESR is a score on a scale (0 to 10) measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR (mm/hour). Flares in disease activity are defined as an increase greater than 1.2 in this score and remission is defined as achieving a DAS28-ESR score of less than 2.6
1.Primary Outcome
Title Change From Baseline in the Disease Activity Score- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 48
Hide Description The DAS28-ESR is a score on a scale (0 to 10) that is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR (mm/hour). Lower score indicates less disease activity. Flares in disease activity are defined as an increase in this score of greater than 1.2 and remission is defined as achieving a DAS28-ESR score of less than 2.6.
Time Frame Baseline (Day 0), Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits
Arm/Group Title Rituximab
Hide Arm/Group Description:

Participants to receive an intravenous infusion of rituximab (1 gram ) fourteen days apart, at baseline (Day 0) and at Week 2.

Concomitant treatments to be administered at a dose and frequency prescribed per protocol include methotrexate (MTX) and folic or folinic acid.

Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: Score on a scale
-1.5  (1.5)
2.Primary Outcome
Title Change From Baseline in Tender Joint Count Score at Week 48
Hide Description Tender Joint Count (TJC) is calculated based on tenderness response of 28 joints. TJC possible values range from 0 to 28. A lower TJC indicates less joint tenderness. Change from baseline is computed as Week 48 value minus baseline value. A negative value in change from baseline indicates an improvement.
Time Frame Baseline (Day 0), Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits
Arm/Group Title Rituximab
Hide Arm/Group Description:

Participants to receive an intravenous infusion of rituximab (1 gram ) fourteen days apart, at baseline (Day 0) and at Week 2.

Concomitant treatments to be administered at a dose and frequency prescribed per protocol include methotrexate (MTX) and folic or folinic acid.

Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: Units on a scale
1.3  (8.4)
3.Primary Outcome
Title Change From Baseline in Swollen Joint Count at Week 48
Hide Description Swollen Joint Count (SJC) is calculated based on swelling response of 28 joints. SJC possible values range from 0 to 28. A lower SJC indicates less joint swelling. Change from baseline is computed as Week 48 value minus baseline value. A negative value in change from baseline indicates an improvement.
Time Frame Baseline (Day 0), Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits
Arm/Group Title Rituximab
Hide Arm/Group Description:

Participants to receive an intravenous infusion of rituximab (1 gram ) fourteen days apart, at baseline (Day 0) and at Week 2.

Concomitant treatments to be administered at a dose and frequency prescribed per protocol include methotrexate (MTX) and folic or folinic acid.

Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-4.7  (1.2)
4.Primary Outcome
Title Change From Baseline in Patient’s Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 48
Hide Description Change from Baseline in PAAP-VAS (0 to 100 millimeters visual analog scale, 0 being no pain and 100 being most severe pain) is computed as the value at Week 48 minus the Baseline value. A negative value in change from Baseline indicates an improvement.
Time Frame Baseline (Day 0), Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits
Arm/Group Title Rituximab
Hide Arm/Group Description:

Participants to receive an intravenous infusion of rituximab (1 gram ) fourteen days apart, at baseline (Day 0) and at Week 2.

Concomitant treatments to be administered at a dose and frequency prescribed per protocol include methotrexate (MTX) and folic or folinic acid.

Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: mm
-2.3  (4.7)
5.Primary Outcome
Title Change From Baseline in Patient’s Global Assessment of Disease Activity- Visual Analog Scale (PtGADA-VAS) at Week 48
Hide Description Change from Baseline in PtGADA-VAS (0 to 100 millimeters visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 48 minus the Baseline value. A negative value in change from Baseline indicates an improvement.
Time Frame Baseline (Day 0), Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits
Arm/Group Title Rituximab
Hide Arm/Group Description:

Participants to receive an intravenous infusion of rituximab (1 gram ) fourteen days apart, at baseline (Day 0) and at Week 2.

Concomitant treatments to be administered at a dose and frequency prescribed per protocol include methotrexate (MTX) and folic or folinic acid.

Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: mm
-1.2  (4.6)
6.Primary Outcome
Title Change From Baseline in Physician’s Global Assessment of Patient’s Disease Activity- Visual Analog Scale (PhGADA-VAS) at Week 48
Hide Description Change from Baseline in PhGADA-VAS (0 to 100 millimeters visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 48 minus the Baseline value. A negative value in change from Baseline indicates an improvement.
Time Frame Baseline (Day 0), Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits
Arm/Group Title Rituximab
Hide Arm/Group Description:

Participants to receive an intravenous infusion of rituximab (1 gram ) fourteen days apart, at baseline (Day 0) and at Week 2.

Concomitant treatments to be administered at a dose and frequency prescribed per protocol include methotrexate (MTX) and folic or folinic acid.

Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: mm
-2.4  (1.7)
7.Primary Outcome
Title Change From Baseline in the Short Form 36 (SF-36) Physical and Mental Health Component Summary Scores (PCS and MCS) at Week 48
Hide Description SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from baseline is computed as the value at Week 48 minus the baseline value. A positive value in change from Baseline indicates an improvement and a negative value worsening.
Time Frame Baseline (Day 0), Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits
Arm/Group Title Rituximab
Hide Arm/Group Description:

Participants to receive an intravenous infusion of rituximab (1 gram ) fourteen days apart, at baseline (Day 0) and at Week 2.

Concomitant treatments to be administered at a dose and frequency prescribed per protocol include methotrexate (MTX) and folic or folinic acid.

Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Change in Short-Form-36 Physical Health Score 14.5  (4.3)
Change in Short-Form-36 Mental Health Score -1.2  (12.8)
8.Primary Outcome
Title Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 48
Hide Description HAQ-DI is derived based on the mean of individual scores in 8 categories of daily living activities (using 20 questions). Each question is scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). In addition, category scores are modified if an aid or device is used, for example, a walker or wheelchair, or help is received from another person in the daily living activities. If an aid or device is used or help is received then a category score of 0 or 1 increases to a category score of 2. A category score of 3 remains a 3 regardless of aids, devices, or help. Scores from each of the 8 categories are totaled. The total score can range from 0 to 24. Change from baseline is computed as the total score at Week 48 minus the baseline total score. A negative value in change from baseline indicates an improvement.
Time Frame Baseline (Day 0), Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits
Arm/Group Title Rituximab
Hide Arm/Group Description:

Participants to receive an intravenous infusion of rituximab (1 gram ) fourteen days apart, at baseline (Day 0) and at Week 2.

Concomitant treatments to be administered at a dose and frequency prescribed per protocol include methotrexate (MTX) and folic or folinic acid.

Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-0.9  (0.3)
9.Primary Outcome
Title Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 48
Hide Description ESR is a blood test used to monitor therapy in inflammatory diseases such as rheumatoid arthritis and reflects acute phase reactant levels. Active disease in RA is defined by an ESR greater than 30 mm/hr. Change from baseline is computed as the value at Week 48 minus the baseline value. A negative value in change from baseline indicates an improvement.
Time Frame Baseline (Day 0), Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits
Arm/Group Title Rituximab
Hide Arm/Group Description:

Participants to receive an intravenous infusion of rituximab (1 gram ) fourteen days apart, at baseline (Day 0) and at Week 2.

Concomitant treatments to be administered at a dose and frequency prescribed per protocol include methotrexate (MTX) and folic or folinic acid.

Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: mm/hr
-24.7  (15.9)
Time Frame From the start of steroid taper, when applicable, and otherwise, from 1.)time of the 1st invasive screening procedure (knee arthroscopy) until participant study completion (Wk 48) or 2.)30 days after a participant prematurely withdraws from the study.
Adverse Event Reporting Description This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003).
 
Arm/Group Title Rituximab
Hide Arm/Group Description Participants to receive an intravenous infusion of rituximab (1 gram ) fourteen days apart, at baseline (Day 0) and at Week 2. Concomitant treatments to be administered at a dose and frequency prescribed per protocol include methotrexate (MTX) and folic or folinic acid.
All-Cause Mortality
Rituximab
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Rituximab
Affected / at Risk (%) # Events
Total   1/4 (25.00%)    
Respiratory, thoracic and mediastinal disorders   
Hypoxia  1  1/4 (25.00%)  1
Laryngospasm  1  1/4 (25.00%)  1
Pulmonary oedema  1  1/4 (25.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rituximab
Affected / at Risk (%) # Events
Total   4/4 (100.00%)    
Cardiac disorders   
Tachycardia  1  1/4 (25.00%)  1
Gastrointestinal disorders   
Nausea  1  1/4 (25.00%)  1
Vomiting  1  1/4 (25.00%)  1
General disorders   
Infusion related reaction  1  2/4 (50.00%)  2
Infections and infestations   
Parvovirus infection  1  1/4 (25.00%)  1
Musculoskeletal and connective tissue disorders   
Synovial cyst  1  1/4 (25.00%)  1
Nervous system disorders   
Dizziness  1  1/4 (25.00%)  1
Vascular disorders   
Hypertension  1  1/4 (25.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
The trial terminated early due to rituximab’s risk-benefit ratio for individuals with early active Rheumatoid Arthritis. Mechanistic samples were not processed and corresponding endpoints were not assessed. Only descriptive statistics are presented.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Associate Director, Clinical Research Program
Organization: DAIT/NIAID
Phone: 301-594-7669
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00396812     History of Changes
Other Study ID Numbers: DAIT ARA04
First Submitted: November 6, 2006
First Posted: November 8, 2006
Results First Submitted: October 11, 2012
Results First Posted: November 14, 2012
Last Update Posted: February 12, 2013