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.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: SAR113945; Drug: placebo

Detailed Description

- 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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Investigational Site Number 276001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: placebo; Pharmaceutical form:Injection Route of administration: Intra-articular
EXPERIMENTAL: SAR113945 - Dose 1	Drug: SAR113945; Pharmaceutical form:Injection Route of administration: Intra-articular
EXPERIMENTAL: SAR113945 - Dose 2	Drug: SAR113945; Pharmaceutical form:Injection Route of administration: Intra-articular
EXPERIMENTAL: SAR113945 - Dose 3	Drug: SAR113945; Pharmaceutical form:Injection Route of administration: Intra-articular

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
Pain, Stiffness and Physical Function sub-scales from the WOMAC Index	during 24 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): August 1, 2012

Study Registration Dates

• First Submitted: October 29, 2011
• First Submitted That Met QC Criteria: October 29, 2011
• First Posted (ESTIMATE): November 2, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): August 23, 2012
• Last Update Submitted That Met QC Criteria: August 22, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: TDU11685; 2011-003232-31 (EUDRACT_NUMBER); TDU11685/ACT12505 (OTHER: sanofi-aventis other study code); U1111-1121-3831 (OTHER: UTN)