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Human TNFa-Induced Pre-B Cell Bone Marrow Emigrants

Phase 4
18 Years
Open (Enrolling)
Rheumatoid Arthritis

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Trial Information

Human TNFa-Induced Pre-B Cell Bone Marrow Emigrants

Primary Objective: The primary objective of the study is to identify early B cell bone
marrow emigrants in the peripheral blood of adults with rheumatoid arthritis (RA) receiving

Hypotheses: We believe that the peripheral blood of RA patients contain early B cell bone
marrow emigrants. We believe that these early B cell bone marrow emigrants are induced by

Primary Endpoint: The primary endpoint of the study is quantification of CD34+/CD19+ early
B cell bone marrow emigrants in the peripheral blood of subjects.

Study Design: Open-label, One Arm, Phase IV study of 12 RA patients with active disease
receiving etanercept.

Inclusion Criteria:

- Rheumatoid arthritis (RA) patients will be eligible for the study if they meet ACR
criteria for a diagnosis of RA (Arnett et al. 1988. The American Rheumatism
Association 1987 revised criteria for the classification of rheumatoid arthritis.
Arthritis & Rheumatism 31:315.) and have active disease (≥ 6 tender and/or swollen

- Subjects must be ≥ 18 years of age.

- Subjects must be rheumatoid factor (RF) positive (any RF titer greater than the upper
limits of normal) and/or anti-CCP antibody positive (any anti-CCP titer greater than
the upper limits of normal). Subjects must have a negative TB skin test at entry
into the study or a negative screening chest x-ray if the PPD test is inconclusive
(borderline, reactive but non-diagnostic) or in prior BCG inoculated subjects.
Female subjects of child bearing potential (excludes those that are surgically
sterile or at least 5 years postmenopausal) must have a negative pregnancy test
(serum β-HCG). Sexually active subjects of childbearing potential must agree to use
medically acceptable forms of contraception during screening and throughout the

- Subjects or a designee must have the ability to self-inject ENBREL or a care-giver at
home who can administer subcutaneous injections. Subjects must be willing to remain
on ENBREL (50 mg SQ qweek) for at least 12 weeks and have not taken anti-rheumatic
agents (DMARDS and/or corticosteroids) besides NSAIDs for the previous 4 weeks.

- The subject must be able and willing to give written informed consent and comply with
the requirements of the study protocol and must authorize release and use of
protected health information. Before any study-specific procedure, the appropriate
written informed consent must be obtained.

Exclusion Criteria:

- RA patients will be excluded if they have a history of congestive heart failure,
recurrent or active infection, a positive PPD, history of neurologic disease, Felty's
syndrome, hematologic malignancy or liver disease.

- RA patients will be excluded if they have a WBC count < 4.0, Hct < 30 or liver
profile abnormalities (> 2x normal values of AST, ALT, TBili and/or APhos).

- RA patients will be excluded if they have been previously treated with anti-TNFα
therapy (ENBREL, infliximab or adalimumab), IL-1ra, abatacept or B and T cell
depleting therapies including rituximab or alemtuzumab. Subjects who have previously
received other DMARD therapies including methotrexate, leflunomide, sulfasalazine,
hydroxychloroquine, gold, penicillamine, cyclosporine A, and cyclophosphamide must
not have taken one of these medications within the past 30 days prior to instituting

- General: Subject is currently enrolled in another investigational device or drug
trial(s), or subject has received other investigational agent(s) within 28 days of
baseline visit. Subjects who have known hypersensitivity to Enbrel or any of its
components or who is known to have antibodies to etanercept.

Prior or concurrent cyclophosphamide therapy. Concurrent sulfasalazine therapy. Known
HIV-positive, mycobacterial disease, active severe infections, untreated Lyme disease,
severe comorbidities, history of TB or TB exposure, chronic hepatitis B or hepatitis C,
SLE, history of multiple sclerosis, transverse myelitis, optic neuritis or epilepsy,
history of recent alcohol or substance abuse (< 1 year), pregnant or lactating females
and/or use of a live vaccine 90 days prior to, or during this study.

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Outcome Measure:

The primary objective of the study is to quantify early B cell bone marrow emigrants in the peripheral blood of adults with rheumatoid arthritis (RA) before and after etanercept therapy.

Outcome Time Frame:

12 weeks

Safety Issue:


Principal Investigator

Marc C Levesque, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh


United States: Institutional Review Board

Study ID:

AMGEN 2006_1112



Start Date:

November 2009

Completion Date:

December 2010

Related Keywords:

  • Rheumatoid Arthritis
  • rheumatoid arthritis
  • B lymphocytes
  • Arthritis
  • Arthritis, Rheumatoid



University of Pittsburgh - Oakland Falk Clinic Pittsburgh, Pennsylvania  15261