Study of Tocilizumab to Treat Polymyalgia Rheumatica

This fifteen-month open label, Phase IIa clinical trial is being conducted to assess the
tolerability, safety and efficacy of a medication called Tocilizumab (Actemra®) in patients
with polymyalgia rheumatica (PMR). The typical symptoms of PMR are muscle pain and stiffness
in the shoulder, neck or hip region. Steroids have traditionally been used to treat this
condition with great success, although long courses of steroids, up to 2 years in many cases,
are often required. This can result in many unwanted side effects including diabetes, high
blood pressure, heart disease, cataracts, weak bones with fractures, weak muscles, skin
bruising, difficulty sleeping and mood disturbances. In this trial, the steroid dosage will
be decreased much more quickly than what is done in routine clinical practice; there is an
expectation that steroid therapy will be withdrawn within six months.

Tocilizumab is a medication already on the market that has been FDA approved in the US and
Japan for the treatment of rheumatoid arthritis, and in Japan it is also approved for certain
types of juvenile idiopathic arthritis (which is like rheumatoid arthritis in children) and
Castleman's disease (which is a rare disease that causes enlarged lymph nodes). It is not FDA
approved to treat polymyalgia rheumatica at this time. In this study, it will be given as an
intravenous infusion once a month for a treatment period of one year. Experiments done on the
blood of patients with PMR show one particular cytokine or small molecule that circulates
throughout the body, interleukin-6, to be elevated in this disease. Tocilizumab is a
medication that is designed to specifically block this cytokine. The co-primary endpoints for
this study include efficacy, as well as evaluations of safety and tolerability.

- Efficacy will be defined by the proportion of patients in Disease Remission (DR) off
corticosteroids, without relapse or recurrence, at six months from trial entry

- Safety and tolerability of Tocilizumab will be evaluated during the fifteen-month study
period by the monitoring of adverse events and immunogenicity surveillance

Disease Remission (DR) will be defined as the disappearance of signs and symptoms of
polymyalgia rheumatica (aching and stiffness of the shoulder, hip girdle, or both) with
normalization of erythrocyte sedimentation rate (ESR<30 mm/hr) and c-reactive protein (CRP
≤1.0 mg/dl), unless elevation of ESR and/or CRP are attributable to causes other than PMR
(i.e., infection).

Disease- Specific Inclusion Criteria:

Patients must meet the following inclusion criteria to be eligible for study entry:

Diagnosed with polymyalgia rheumatica and enrolled within one month of diagnosis.

Disease Specific Exclusion Criteria:

Patients will be excluded from the study based on the following criteria:

- Symptoms or diagnosis of temporal arteritis, including headache, jaw claudication,
hyperesthesia of scalp, abnormal palpated temporal artery, visual disturbances,
temporal artery biopsy positivity

- Concurrent rheumatoid arthritis

- Presence of rheumatoid factor and CCP

- Other inflammatory arthritis or other connective tissue diseases, such as but not
limited to systemic lupus erythematosus, systemic sclerosis, vasculitis, polymyositis,
dermatomyositis, mixed connective tissue disease

- Treatment of polymyalgia rheumatica with more than 20mg of daily prednisone or its
equivalent at the time of screening

- Treatment with more than 30mg of daily prednisone or its equivalent since diagnosis.
Treatment with 30mg of daily prednisone or its equivalent since diagnosis for more
than 2 weeks.

- More than 4 weeks of corticosteroid therapy prior to enrollment

- History of bowel perforation within the past five years.

- Active diverticulitis.

- Pre-existing or recent onset demyelinating disorders