Trial Outcomes & Findings for Rituximab for the Treatment of Early Rheumatoid Arthritis (RA) (NCT NCT00396812)

NCT ID: NCT00396812

Last Updated: 2013-02-12

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 4 participants
• Primary outcome timeframe: Baseline (Day 0), Week 48
• Results posted on: 2013-02-12

Participant Flow

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.

Participant milestones

Measure	Rituximab 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 Study STARTED	4
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Rituximab 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 Study Physician Decision	1

Baseline Characteristics

Rituximab for the Treatment of Early Rheumatoid Arthritis (RA)

Baseline characteristics by cohort

Measure	Rituximab n=4 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	43.3 years STANDARD_DEVIATION 15.4 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants
Disease Activity Score 28 -Erythrocyte Sedimentation Rate (DAS28-ESR)	5.1 Score on a scale STANDARD_DEVIATION 1.3 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0), Week 48

Population: All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits

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.

Outcome measures

Measure	Rituximab n=3 Participants 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.
Change From Baseline in the Disease Activity Score- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 48	-1.5 Score on a scale Standard Deviation 1.5

PRIMARY outcome

Timeframe: Baseline (Day 0), Week 48

Population: All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits

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.

Outcome measures

Measure	Rituximab n=3 Participants 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.
Change From Baseline in Tender Joint Count Score at Week 48	1.3 Units on a scale Standard Deviation 8.4

PRIMARY outcome

Timeframe: Baseline (Day 0), Week 48

Population: All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits

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.

Outcome measures

Measure	Rituximab n=3 Participants 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.
Change From Baseline in Swollen Joint Count at Week 48	-4.7 Units on a scale Standard Deviation 1.2

PRIMARY outcome

Timeframe: Baseline (Day 0), Week 48

Population: All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits

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.

Outcome measures

Measure	Rituximab n=3 Participants 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.
Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 48	-2.3 mm Standard Deviation 4.7

PRIMARY outcome

Timeframe: Baseline (Day 0), Week 48

Population: All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits

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.

Outcome measures

Measure	Rituximab n=3 Participants 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.
Change From Baseline in Patient's Global Assessment of Disease Activity- Visual Analog Scale (PtGADA-VAS) at Week 48	-1.2 mm Standard Deviation 4.6

PRIMARY outcome

Timeframe: Baseline (Day 0), Week 48

Population: All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits

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.

Outcome measures

Measure	Rituximab n=3 Participants 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.
Change From Baseline in Physician's Global Assessment of Patient's Disease Activity- Visual Analog Scale (PhGADA-VAS) at Week 48	-2.4 mm Standard Deviation 1.7

PRIMARY outcome

Timeframe: Baseline (Day 0), Week 48

Population: All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits

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.

Outcome measures

Measure	Rituximab n=3 Participants 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.
Change From Baseline in the Short Form 36 (SF-36) Physical and Mental Health Component Summary Scores (PCS and MCS) at Week 48 Change in Short-Form-36 Physical Health Score	14.5 Units on a scale Standard Deviation 4.3
Change From Baseline in the Short Form 36 (SF-36) Physical and Mental Health Component Summary Scores (PCS and MCS) at Week 48 Change in Short-Form-36 Mental Health Score	-1.2 Units on a scale Standard Deviation 12.8

PRIMARY outcome

Timeframe: Baseline (Day 0), Week 48

Population: All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits

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.

Outcome measures

Measure	Rituximab n=3 Participants 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.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 48	-0.9 Units on a scale Standard Deviation 0.3

PRIMARY outcome

Timeframe: Baseline (Day 0), Week 48

Population: All subjects who receive at least one dose of study treatment and attended Day 0 and Week 48 visits

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.

Outcome measures

Measure	Rituximab n=3 Participants 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.
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 48	-24.7 mm/hr Standard Deviation 15.9

Adverse Events

Rituximab

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rituximab n=4 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Hypoxia	25.0% 1/4 • Number of events 1 • 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. 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).
Respiratory, thoracic and mediastinal disorders Laryngospasm	25.0% 1/4 • Number of events 1 • 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. 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).
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	25.0% 1/4 • Number of events 1 • 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. 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).

Other adverse events

Measure	Rituximab n=4 participants at risk 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.
Cardiac disorders Tachycardia	25.0% 1/4 • Number of events 1 • 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. 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).
Gastrointestinal disorders Nausea	25.0% 1/4 • Number of events 1 • 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. 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).
Gastrointestinal disorders Vomiting	25.0% 1/4 • Number of events 1 • 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. 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).
General disorders Infusion related reaction	50.0% 2/4 • Number of events 2 • 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. 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).
Infections and infestations Parvovirus infection	25.0% 1/4 • Number of events 1 • 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. 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).
Musculoskeletal and connective tissue disorders Synovial cyst	25.0% 1/4 • Number of events 1 • 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. 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).
Nervous system disorders Dizziness	25.0% 1/4 • Number of events 1 • 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. 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).
Vascular disorders Hypertension	25.0% 1/4 • Number of events 1 • 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. 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).

Additional Information

Associate Director, Clinical Research Program

DAIT/NIAID

Phone: 301-594-7669

Email: DAITClinicalTrialsGov@niaid.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place