Safety, Tolerability and Pharmacokinetics of SAR113945 Following Intra-articular Administration in Patients With Knee Osteoarthritis

A Double Blind, Placebo Controlled Ascending Single Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of the IKK Inhibitor, SAR113945, Following Intra-articular Administration in Patients With Knee Osteoarthritis

Primary Objective:

• Assess the safety and tolerability of single intra-articular doses of SAR113945 in patients with knee osteoarthritis.

Secondary Objective:

• Assess systemic exposure of SAR113945 following intra-articular delivery.

Study Overview

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

Detailed Description

The total study duration per subject ranges from 4 to 20 weeks broken down as follows:

• screening within 4 weeks before dosing,
• follow-up of 4 weeks (28 days) after the single dose of study medication,
• prolonged by a maximum of 12 weeks if plasma PK level > Limit Of Quantification (LOQ) at Day 28.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Sanofi-Aventis 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:

• Male patients or female patients of non child-bearing potential, aged at least 40 years with primary knee osteoarthritis having:

  • X-ray or Magnetic Resonance Imaging (MRI) evidence for Kellgren Lawrence Grades II./III joint space narrowing and osteophyte formation,
  • Western Ontario MacMaster (WOMAC) score ≦ 72,
  • American College of Rheumatology (ACR) Clinical and Radiographic criteria for osteoarthritis.

Exclusion criteria:

• Any uncontrolled, chronic condition or laboratory finding which, in the opinion of the Principal Investigator, could potentially put the patient at increased risk.
• Secondary osteoarthritis.
• Moderate/severe renal impairment.
• Underlying hepatobiliary disease and/or elevated Alanine Aminotransferase (ALT) > 3 Upper Limit of Normal range.
• Intra-articular injection within 3 months.
• Presence of local skin abnormality at the affected knee joint.
• Unable to be maintained for at least 2 weeks prior to entry into study on paracetamol or metamizole as analgesic.
• Any Investigational Product within 3 months.
• Any patient unlikely to comply with the requirements of the study.

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 Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR113945; SAR113945, single dose according to dose escalation design	Drug: SAR113945; Pharmaceutical form:injection Route of administration: intra-articular
Placebo Comparator: Placebo; 0.9% saline solution, single dose	Drug: placebo; Pharmaceutical form:injection Route of administration: intra-articular

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Standard safety investigations (Physical examinations, 12 lead ECGs, vital signs (Blood pressure, heart rate, body temperature) and laboratory tests (hematology/coagulation, biochemistry, quantitative urinalysis))		4 weeks up to a maximum of 12 weeks
Examination of skin/soft tissue of injected knee	Any reaction is classified as erythema, oedema, pain, papulae, haematoma and graded none, mild, moderate or severe.	4 weeks up to a maximum of 12 weeks
Examination of knee joint of injected knee	Any reaction is classified as effusion/worsening of effusion, warm and pain.	4 weeks up to a maximum of 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic parameters for SAR113945 and potential metabolites(s) from plasma concentration (i.e. AUC, Cmax, tmax, t1/2)	4 weeks up to a maximum of 16 weeks
Pharmacodynamic parameters (WOMAC Index, biomarkers relating to inflammation and cartilage/bone turnover)	4 weeks

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: April 23, 2010
• First Submitted That Met QC Criteria: April 28, 2010
• First Posted (Estimate): April 29, 2010

Study Record Updates

• Last Update Posted (Estimate): March 23, 2011
• Last Update Submitted That Met QC Criteria: March 22, 2011
• Last Verified: March 1, 2011

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: TDU10820; 2009-017502-36 (EudraCT Number); U1111-1116-5630 (Other Identifier: UTN)