Fasitibant Intra-articular Injection in Patients With Symptomatic Osteoarthritis of the Knee

Study Overview
=================
Brief Summary
-----------------
This study is designed as a double-blind, randomised, placebo-controlled, four parallel arm, dose-finding study, to be conducted in approximately 26 sites, to evaluate the efficacy, safety, tolerability, and pharmacokinetics of single intra-articular (IA) injections of fasitibant in patients with symptomatic osteoarthritis (OA) of the knee. Approximately 400 male and female patients 40-80 years old, with BMI < 30 kg/m² and with a clinical diagnosis of symptomatic primary osteoarthritis of the knee will be randomised to a total of 4 treatment arms. Each arm includes a single intra-articular injection of one of three dosages of fasitibant (low, intermediate and high dose) OR placebo. The randomisation ratio will be 1:1:1:1. The primary efficacy variable will be the change of the Western Ontario and McMaster Universities Visual Analogue Scale 3.1 A (WOMAC VA 3.1 A) (total pain) subscore from baseline up to 2 weeks after randomisation. Safety will be assessed by monitoring adverse events and clinical laboratory tests; local tolerability at the injection site will also be assessed. In addition, the population pharmacokinetics and the exposure-response relationship will be evaluated. The individual experimental clinical phase will last up to maximal 15 weeks encompassing 7 planned visits at site, including screening, randomisation, 4 follow-up visits and the End of study visit.

Official Title
-----------------
A Double-blind, Randomised, Placebo-controlled, Four Parallel Arm, Dose-finding Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Single Intra-articular Injections of Fasitibant in Patients With Symptomatic Osteoarthritis of the Knee.

Conditions
-----------------
Knee Osteoarthritis

Intervention / Treatment
-----------------
* Drug: Fasitibant- low dose
* Drug: Fasitibant- intermediate dose
* Drug: Fasitibant- high dose
* Drug: Placebo comparator


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patients aged 40 to 80 years with BMI < 30 kg/m² Patient with Kellgren-Lawrence Grade 2 to 3, symptomatic primary osteoarthritis at the index knee (ACR criteria), for which an IA treatment is indicated Pain of moderate to severe intensity, even if treated with chronic doses of non steroidal antinflammatory drugs Exclusion Criteria: History of hypersensitivity/allergy to drugs including paracetamol and to disinfectants Any pharmacological treatment of concomitant disease(s) started or changed during 4 weeks prior to randomisation, or likely to be changed during the course of the study Use of systemic or topical corticosteroids > 10 mg prednisolone equivalent per day, or immunosuppressant drugs Current use of any pain or OA medication (e.g. NSAIDs, COX-2 inhibitors, analgesics, antidepressive agents), including topical treatments Viscosupplementation to the target knee administered < 4 months prior to randomisation and/or scheduled during the course of the study Evidence of clinically significant hepatic disease or of moderate or severe renal insufficiency Current use of any medications that are substrate of CYP3A4 and/or moderate or strong CYP3A4 inhibitors Patients with any clinically relevant or unstable disease, or malignant neoplasms that, in the opinion of the Investigator, may pose the patient at risk, or confound the efficacy and safety results of the study Patients with any clinically relevant abnormal safety laboratory test results, and/or abnormalities in vital signs, and/or ECG parameters Pregnant and breastfeeding women Any sign of significant immunodeficiency, systemic infection, knee infection or knee bursitis Patients with bleeding diathesis or on therapy with anticoagulants

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fasitibant low dose<br>Drug: solution for intra-articular injection | Drug: Fasitibant- low dose<br>* Single intra-articular injection of low dose of fasitibant<br>|
| Experimental: Fasitibant intermediate dose<br>Drug: solution for intra-articular injection | Drug: Fasitibant- intermediate dose<br>* Single intra-articular injection of intermediate dose of fasitibant<br>|
| Experimental: Fasitibant high dose<br>Drug: solution for intra-articular injection | Drug: Fasitibant- high dose<br>* Single intra-articular injection of high dose of fasitibant<br>|
| Placebo Comparator: PLACEBO<br>Drug: solution for intra-articular injection | Drug: Placebo comparator<br>* Single intra-articular injection of placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in WOMAC A | The validated Western Ontario and McMaster University questionnaire (WOMAC) was used to measure total knee pain choosing its visual analogue scale version (VAS). The WOMAC VA 3.1 A subscore (WOMAC A) ranges from 0 to 500 mm (summing up five VAS 0-100 mm) with higher scores indicating more pain. | from baseline up to 2 weeks after randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in WOMAC INDEX | The WOMAC VA 3.1 Index score (WOMAC INDEX) is the sum of WOMAC A (total pain), WOMAC B (stiffness) and WOMAC C (functional impairment) subscores. The WOMAC INDEX score ranges from 0 to 2400 mm, with higher scores indicating higher disease burden. | from baseline up to 6 weeks after randomisation | 
| Responder Rate According to OMERACT-OARSI Criteria | Percentage of responders according to Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria (OMERACT-OARSI criteria). Patients with at least 50 % improvement in pain or in function scores are considered responders. Alternatively, patients are considered responders if they show at least 20% improvement in at least two of the following scores: pain, function and Patients's Global Assessment (PGA) scores. | from baseline up to 6 weeks after randomisation | 
| Euro Quality of Life Questionnaire (EQ-5D-5L) Responder Rate | Response based on change ≥ 20 % from baseline for EQ-5D-5L index value | from baseline up to 6 weeks after randomisation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Osteoarthritis, Knee, Arthritis, WOMAC, Injections, intra-articular, Fasitibant, MEN 16132