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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

Phase 1/Phase 2
18 Years
Not Enrolling
Rheumatoid Arthritis

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Trial Information

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

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.

Inclusion Criteria:

- 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

Exclusion Criteria:

- Allergy to methotrexate (MTX)

- Previous exposure to anti-CD20 monoclonal antibody (mAb) or other type(s) of mAb

- 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

- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome 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.

Outcome Time Frame:

Baseline (Day 0), Week 48

Safety Issue:


Principal Investigator

Christopher Striebich, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Rheumatology Division, University of Colorado Health Sciences Center


United States: Food and Drug Administration

Study ID:




Start Date:

November 2006

Completion Date:

July 2009

Related Keywords:

  • Rheumatoid Arthritis
  • Autoimmune disease
  • Biologic response modifiers
  • Disease-modifying antirheumatic drugs (DMARDS)
  • Immune system
  • Rheumatoid arthritis (RA)
  • Rituximab (anti-CD20 monoclonal antibodies)
  • Arthritis
  • Arthritis, Rheumatoid



University of Colorado Health Sciences Center Denver, Colorado  80262