VELVET (Veltuzumab Various Doses Exploratory Trial), a Randomized, Double Blind, Placebo Controlled, Multicentre, Multinational Phase II Dose Range Finding Trial in Subjects With Moderate to Severe Rheumatoid Arthritis Insufficiently Controlled With Either Methotrexate Alone or Methotrexate Plus Anti-tumour Necrosis Factor Biological Treatment, Comparing 3 Different Subcutaneous Dosages of Anti-CD20 Monoclonal Antibody Veltuzumab to Placebo as an add-on Therapy to Methotrexate.

Main

Inclusion Criteria:

- Active disease defined as:

- Diagnosis of RA using the ACR criteria for the classification of RA for at least
6 months prior to trial entry (Screening, Visit 1)

- Swollen joint count (SJC) ≥ 6 and tender joint count (TJC) ≥ 6 referred to as
the 66/68 - joint count system

- High sensitivity C-reactive protein (hs-CRP) ≥ 15 mg/L and/or an erythrocyte
sedimentation rate (ESR) ≥ 28 mm/hour

- Positive rheumatoid factor (RF) ≥ 14 IU/mL and/or anti-cyclic citrullinated
protein (CCP) ≥ 20 U

- An inadequate response (insufficient initial or loss of response and/or intolerance
to at least one administration of these agents) to previous or current treatment with
either MTX alone or MTX plus anti-tumour necrosis factor alpha (anti-TNFα) biological
treatment. Subjects should not have received more than two different anti-TNFα
therapies.

- Receiving MTX 15-25 mg/week (oral or parenteral) for at least 20 weeks, including the
last 6 weeks prior to Baseline (Visit 3, Day 1) at a stable dose via the same route
of administration and formulation. A stable dose of 12.5 mg of MTX is acceptable if
the MTX dose has been reduced for reasons of toxicity, e.g. pulmonary, hepatic or
haematological toxicity. MTX co-medication will be continued until the end of the
trial (Week 48)

Main Exclusion Criteria:

- Primary or secondary immunodeficiency including HIV infection

- Evidence of acute or chronic infection with hepatitis B and C virus (HBV and HCV)

- Evidence (e.g. chest X-ray [posterior-anterior view], tuberculin/ PPD skin test,
etc., according local guidelines) and/or history of active tuberculosis (TB), prior
to successfully completing an anti-TB treatment. X-rays performed prior to inclusion
(Screening, Visit 1) into the trial are accepted provided they were done within 3
months prior to Screening (Visit 1). Subjects with latent TB infection (LTBI) can be
included

- Significant cardiac disease or history of severe COPD

- Diabetes mellitus type 1 or unstable type 2

- History of cancer within the last 5 years treated with anti-cancer chemotherapy