Safety and Preliminary Efficacy of MOR103 in Patients With Active Rheumatoid Arthritis

A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Preliminary Clinical Activity and Immunogenicity of Multiple Doses of MOR103 Administered Intravenously to Patients With Active Rheumatoid Arthritis

GM-CSF is considered to have a key role in the initiation and progression of arthritic inflammation. The purpose of this study is to evaluate the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of multiple doses of MOR103, a human antibody to GM-CSF, in patients with active rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that affects 0.5% to 1% of the adult population world wide. RA primarily affects the joints and is characterized by chronic inflammation of the synovial tissue, which eventually leads to the destruction of cartilage, bone and ligaments and can cause joint deformity.

Pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFα), interleukin (IL)-1, IL-6 and granulocyte macrophage colony stimulating factor (GM-CSF), which lead to the activation and proliferation of immune cells, are found to be increased in the inflamed joint. Several preclinical findings support an anti-GM-CSF therapy for RA.

Inclusion Criteria:

• Rheumatoid arthritis (RA) per revised 1987 ACR criteria
• Active RA: ≥3 swollen and 3 tender joints with at least 1 swollen joint in the hand, excluding the PIP joint
• CRP > 5.0 mg/L (RF and anti-CCP seronegative); CRP >2 mg/l (RF and/or anti-CCP seropositive)
• DAS28 ≤ 5.1
• Stable regimen of concomitant RA therapy (NSAIDs, steroids, non- biological DMARDs).
• Negative PPD tuberculin skin test

Exclusion Criteria:

• Previous therapy with B or T cell depleting agents other than Rituximab (e.g. Campath). Prior treatment with Rituximab, TNF-inhibitors, other biologics (e.g. anti-IL-1 therapy) and systemic immunosuppressive agents is allowed with a washout period.
• Any history of ongoing, significant or recurring infections
• Any active inflammatory diseases other than RA
• Treatment with a systemic investigational drug within 6 months prior to screening
• Women of childbearing potential, unless receiving stable doses of methotrexate or leflunomide
• Significant cardiac or pulmonary disease (including methotrexate- associated lung toxicity)
• Hepatic or renal insufficiency