Safety of Single Doses of SAR113945 and Efficacy and Safety of a New Formulation Given Into the Knee in Osteoarthritis Patients / Part I

A Two Part Protocol to Assess, Using Double Blind Placebo Control, the Safety, Tolerability, and Pharmacokinetics of Ascending Single Doses of a New Intra-articular Administration Formulation of SAR113945 (IKK Inhibitor) Followed by Assessment of Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose in Patients With Knee Osteoarthritis

Study objectives:

• Part 1 TDU11685 To assess in patients with knee Osteoarthritis (OA), the safety, tolerability and pharmacokinetics (PK) of single intra-articular doses of SAR113945.
• Part 2 ACT12505 To assess in patients with knee OA, the efficacy, safety and tolerability of a single intra-articular dose of SAR113945.

- Screening will be performed within 28 days of dosing. Following the single dose of study medication, the study period for each patient will be 168 days.

Inclusion criteria:

- Diagnosis of primary knee osteoarthritis, based upon the following:

• X-ray or Magnetic Resonance Imaging (MRI) evidence within the last 6 months for joint space narrowing and osteophyte formation
• Patients will be Kellgren and Lawrence classification II/III, and total Western Ontario McMaster (WOMAC) score 24 -72.
• Patients fulfilling the American College of Rheumatology Clinical and Radiographic criteria for Osteoarthritis.

Exclusion criteria:

• Patients younger than 40 years
• Women of child bearing potential.
• Women either sterilized for more than 3 months, or post-menopausal for more than 12 months. Menopause is defined as over age of 60 years or being amenorrheic for at least 2 years with plasma FSH level >30 IU/L.
• Secondary osteoarthritis: e.g., autoimmune disease, joint dysplasia, aseptic osteonecrosis, acromegaly, Paget's disease, Ehlers-Danlos Syndrome, Gaucher's disease, Stickler's syndrome, joint infection, haemophilia, haemochromatosis, calcium pyrophosphate deposition disease, or neuropathic arthropathy.
• Presence of local skin abnormality at the affected knee joint.
• Intra-articular injection within 3 months.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.