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Rheumatoid ArthritisPhase 1/2NCT00396812

Rituximab for the Treatment of Early Rheumatoid Arthritis (RA)

A Phase 1/2 study testing Rituximab in people with Rheumatoid Arthritis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, pain, stiffness, damage, and ultimately loss of joint function. Scientists estimate that about 1.3 million people (0.6 percent) of the U.S. adult population have RA. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
Nov 2006to Jul 2009
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of RA, as defined by fulfilling at least four of seven American College of Rheumatology (ACR) criteria
  • Positive for rheumatoid factor (RF) and/or anticyclic citrullinated peptide (CCP)
  • The presence of arthritis symptoms for more than 6 weeks but less than 1 year
  • Active RA, as defined by at least four swollen joints, at least four tender joints, and either an erythrocyte sedimentation rate (ESR) of greater than 30 mm/hr OR C-reactive protein level greater than 1.0 mg/dL (normal less than 0.4)
  • Willing to adhere to the study requirements
  • Willing to use acceptable effective forms of contraception

Who cannot join

  • Allergy to methotrexate (MTX)
  • Previous exposure to anti-CD20 monoclonal antibody (mAb) or other type(s) of mAb therapy
  • Previous disease-modifying anti-rheumatic drugs (DMARD) therapy
  • Previous use of a biologic agent
  • Currently taking daily oral steroid doses of greater than 7.5 milligrams (mg)
  • Receipt of intra-articular injections within 4 weeks prior to study entry
Show all 23Show fewer
  • Current peptic ulcer disease (PUD)
  • Unwilling to stop drinking alcohol (ETOH)
  • History of alcohol or substance abuse
  • Active infection, or chronic or persistent infection that might worsen with immunosuppressive treatment (e.g., Human Immunodeficiency Virus [HIV], hepatitis B virus [HBV], hepatitis C virus [HCV], tuberculosis [TB])
  • Interstitial lung disease observed by chest x-ray [chest radiograph]
  • Known coronary artery disease or significant cardiac arrhythmias or severe congestive heart failure (New York Heart Association [NYHA] classes III or IV)
  • Definitive diagnosis of another autoimmune rheumatologic disease (e.g., systemic lupus erythematosus [SLE], scleroderma, primary Sjögren's syndrome, primary vasculitis)
  • History of immunoglobulin E (IgE)-mediated or non-IgE-mediated hypersensitivity or known anaphylaxis to mouse proteins
  • History of cancer. Exception: participants with previous resected basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ Grade I cervical cancer within 5 years prior to study entry are not excluded from study eligibility
  • History of positive purified protein derivative (PPD) test (i.e., positive tuberculosis [TB] test) without treatment for TB infection or chemoprophylaxis for TB exposure
  • History of inflamed pancreas
  • Live vaccine within 3 months of study entry
  • Certain abnormal laboratory values
  • Require certain medications
  • Any psychiatric disorder that would prevent a participant from providing informed consent
  • Any condition or treatment (including biologic therapies) that, in the opinion of the investigator, may place the participant at unacceptable risk during the study
  • Pregnancy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Colorado Health Sciences Center

    Denver, Colorado, 80262

Other trials in United States

About this study

Official title: An Open Label, Single Arm, Single Center, Phase I/II Trial of Rituximab (a Monoclonal Antibody to CD20) for the Treatment of Early Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, pain, stiffness, damage, and ultimately loss of joint function. Scientists estimate that about 1.3 million people (0.6 percent) of the U.S. adult population have RA. Current therapies target the immune system early in the disease process before joint damage occurs, and include drugs such as methotrexate (MTX) and tumor necrosis factor (TNF)-blocking agents. Rituximab is a disease-modifying antirheumatic drug (DMARD) recently approved by the FDA for use in combination with MTX for treatment of moderately to severely active RA in patients who have had an inadequate response to TNF-blocking agents, in an effort to try to slow the course of the disease. This study will examine the effects of rituximab on the immune response and disease activity in participants with early RA who have not been treated with any disease-modifying agent. In addition, the safety and tolerability of rituximab in this population will be examined.

Read the detailed description

RA is an inflammatory disease that causes pain, swelling, stiffness, and loss of function in the joints. It occurs when the immune system, which normally defends the body from invading organisms, turns its attack against the membrane lining the joints. RA is commonly managed by DMARDs initiated early in the disease process, before irreversible joint damage occurs. The most common DMARD prescribed in the United States is MTX; this drug is well tolerated and has better efficacy compared to other DMARDs, but is inadequate in providing lasting improvement in individuals with RA. In patients with an inadequate response to MTX alone, the use of biologic agents, including TNF-blocking agents in combination with MTX, has become a standard therapeutic approach.

Rituximab (anti-CD20) is a man-made antibody used to treat certain types of cancer. The drug blocks the CD20 antigen found on the surface of B cells and is known to deplete B cells when administered intravenously. Previous research suggests B-cell activity is important in pathogenesis of RA, so B-cell depletion may decrease inflammation and other symptoms of RA. Rituximab has recently been approved by the FDA for use in combination with MTX for treatment of patients with moderately to severely active RA who have had an inadequate response to TNF-blocking agents. This study will examine the effects of rituximab on the immune response and disease activity in patients with early active RA who have not been treated with any disease-modifying agent. Levels of B and T cells and other markers of disease activity will be monitored during the study. The safety and tolerability of rituximab in this DMARD-naive population will be examined.

The expected duration of this study is 2.5 years. All participants will receive two intravenous infusions of rituximab in an outpatient setting at study entry and Week 2. Throughout the study, participants will receive MTX, systemic corticosteroids, and folic or folinic acid. MTX dosing will be re-evaluated by disease activity scores every month until Month 6 and again at Months 8, 10, and 12. Systemic corticosteroid doses will be modified based on the participant's health while in the study. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is permitted, but NSAID doses should not be changed during the study, if at all possible. NSAIDs will not be provided by this study.

There will be a maximum of 2 screening visits before study treatment, a baseline visit (Day 0), and 11 study visits. A physical exam, assessment for adverse events, and blood collection will occur at all study visits. Kidney and liver function tests and rheumatologic evaluations will occur at most study visits; participants will also be asked to complete a questionnaire on their health at most study visits. Arthroscopy (knee biopsy) on the more inflamed knee will occur at baseline and Month 3. Participants will be contacted by telephone the day after each arthroscopy and rituximab infusion.

Being tested
Rituximab
Keywords
Autoimmune disease, Biologic response modifiers, Disease-modifying antirheumatic drugs (DMARDS), Immune system, Rheumatoid arthritis (RA), Rituximab (anti-CD20 monoclonal antibodies)
Medical subject headings
Arthritis, Rheumatoid, Autoimmune Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabDrug

    Also called Anti-CD20 antibody therapy, Rituxan

    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.

Study groups in NCT00396812
Study groupRoleWhat they receive
RituximabExperimentalNot described
Receives: Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in the Disease Activity Score- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 48

    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.

    Measured: Baseline (Day 0), Week 48

  2. Change From Baseline in Tender Joint Count Score at Week 48

    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.

    Measured: Baseline (Day 0), Week 48

  3. Change From Baseline in Swollen Joint Count at Week 48

    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.

    Measured: Baseline (Day 0), Week 48

  4. Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 48

    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.

    Measured: Baseline (Day 0), Week 48

  5. Change From Baseline in Patient's Global Assessment of Disease Activity- Visual Analog Scale (PtGADA-VAS) at Week 48

    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.

    Measured: Baseline (Day 0), Week 48

  6. Change From Baseline in Physician's Global Assessment of Patient's Disease Activity- Visual Analog Scale (PhGADA-VAS) at Week 48

    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.

    Measured: Baseline (Day 0), Week 48

  7. Change From Baseline in the Short Form 36 (SF-36) Physical and Mental Health Component Summary Scores (PCS and MCS) at Week 48

    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.

    Measured: Baseline (Day 0), Week 48

  8. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 48

    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.

    Measured: Baseline (Day 0), Week 48

  9. Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 48

    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.

    Measured: Baseline (Day 0), Week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Nov 2006 (estimated)
  2. Study startNov 2006
  3. Primary completionJul 2009
  4. Study completionJul 2009

Why it stopped: The perceived risk-benefit ratio for individuals with early active RA

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00396812
Sponsor's protocol ID
DAIT ARA04
Status last verified
Feb 2013
First submitted
6 Nov 2006
Last updated
12 Feb 2013

Publications

  • De Vita S, Quartuccio L. Treatment of rheumatoid arthritis with rituximab: an update and possible indications. Autoimmun Rev. 2006 Aug;5(7):443-8. doi: 10.1016/j.autrev.2006.02.007. Epub 2006 Mar 15.

    PubMed 16920570

  • Eisenberg R, Albert D. B-cell targeted therapies in rheumatoid arthritis and systemic lupus erythematosus. Nat Clin Pract Rheumatol. 2006 Jan;2(1):20-7. doi: 10.1038/ncprheum0042.

    PubMed 16932648

  • Isenberg DA. B cell targeted therapies in autoimmune diseases. J Rheumatol Suppl. 2006 May;77:24-8.

    PubMed 16652442

  • Looney RJ. B cell-targeted therapy for rheumatoid arthritis: an update on the evidence. Drugs. 2006;66(5):625-39. doi: 10.2165/00003495-200666050-00004.

    PubMed 16620141

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Rituximab in people with Rheumatoid Arthritis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in the Disease Activity Score- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 48 (time frame: Baseline (Day 0), Week 48). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00396812, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2013.

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