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

Study Overview
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Brief Summary
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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.

Detailed Description
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- 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.

Official Title
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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

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Drug: SAR113945
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAR113945 - Dose 1<br> | Drug: SAR113945<br>* Pharmaceutical form:Injection Route of administration: Intra-articular<br>|
| Experimental: SAR113945 - Dose 2<br> | Drug: SAR113945<br>* Pharmaceutical form:Injection Route of administration: Intra-articular<br>|
| Experimental: SAR113945 - Dose 3<br> | Drug: SAR113945<br>* Pharmaceutical form:Injection Route of administration: Intra-articular<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* Pharmaceutical form:Injection Route of administration: Intra-articular<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain, Stiffness and Physical Function sub-scales from the WOMAC Index |  | during 24 weeks | 
| Number of patients reporting Adverse Events of special interest: tolerability at the site of injection and in the knee + other events reported by the patient |  | during 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (Cmax) |  | during 24 weeks | 
| Pharmacokinetics (AUC) |  | during 24 weeks | 
| Pharmacokinetics (t1/2) |  | during 24 weeks | 
| synovial fluid levels |  | during 24 weeks |