Fasitibant Intra-articular Injection in Patients With Symptomatic Osteoarthritis of the Knee
- Conditions
- Knee Osteoarthritis
- Interventions
- Drug: Placebo comparatorDrug: Fasitibant- low doseDrug: Fasitibant- high doseDrug: Fasitibant- intermediate dose
- Registration Number
- NCT02205814
- Lead Sponsor
- Menarini Group
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 436
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PLACEBO Placebo comparator Drug: solution for intra-articular injection Fasitibant low dose Fasitibant- low dose Drug: solution for intra-articular injection Fasitibant high dose Fasitibant- high dose Drug: solution for intra-articular injection Fasitibant intermediate dose Fasitibant- intermediate dose Drug: solution for intra-articular injection
- Primary Outcome Measures
Name Time Method Change in WOMAC A from baseline up to 2 weeks after randomisation 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.
- Secondary Outcome Measures
Name Time Method Change in WOMAC INDEX from baseline up to 6 weeks after randomisation 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.
Responder Rate According to OMERACT-OARSI Criteria from baseline up to 6 weeks after randomisation 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.
Euro Quality of Life Questionnaire (EQ-5D-5L) Responder Rate from baseline up to 6 weeks after randomisation Response based on change ≥ 20 % from baseline for EQ-5D-5L index value
Trial Locations
- Locations (25)
Physicians Research Options, LLC
🇺🇸Draper, Utah, United States
Tekton Research
🇺🇸Austin, Texas, United States
Spokan Joint Replacement Center
🇺🇸Spokane, Washington, United States
Blair Orthopaedic Associates
🇺🇸Altoona, Pennsylvania, United States
Clinical Research Hamburg GmbH
🇩🇪Hamburg, Germany
Synexus Clinical Research GmbH, Research Centre Leipzig
🇩🇪Leipzig, Germany
Revmatologie s.r.o.
🇨🇿Brno, Czech Republic
AmBeNet GmbH
🇩🇪Leipzig, Germany
Dipartimento di Medicina Interna - SOD di Reumatologia Azienda - Ospedaliero Universitaria Careggi
🇮🇹Firenze, Tuscany, Italy
Avail Clinical Research, LLC
🇺🇸Deland, Florida, United States
Columbus Clinical Research
🇺🇸Columbus, Ohio, United States
Synexus Clinical Research GmbH, Research Centre Frankfurt
🇩🇪Frankfurt, Germany
Synexus Clinical Research GmbH, Research Centre Bochum
🇩🇪Bochum, Germany
Synexus Clinical Research GmbH, Research Centre Berlin
🇩🇪Berlin, Germany
Colorado Orthopaedic Consultants
🇺🇸Englewood, Colorado, United States
Azienda Ospedaliero-Universitaria S.Anna/ Unità Operativa Complessa e Sezione di Reumatologia/Dipartimento di Medicina Clinica e Sperimentale
🇮🇹Cona, Italy
Azienda Ospedaliera di Perugia/Policlinico di Monteluce/Unità Operativa diagnosi e cura delle malattie reumatiche
🇮🇹Perugia, Italy
Ospedale Galateo U.O. di Reumatologia
🇮🇹Lecce, Italy
Ospedale Fornaroli/Unità Complessa di Reumatologia
🇮🇹Magenta, Italy
Ospedale Luigi Sacco, Azienda Ospedaliera, Polo Universitario/Unità Operativa Complessa di Reumatologia
🇮🇹Milano, Italy
Centro Ricerche Cliniche di Verona
🇮🇹Verona, Italy
Tucson Orthopaedic Institute
🇺🇸Tucson, Arizona, United States
Institute of Rheumatology, Charles University Faculty Hospital
🇨🇿Prague, Czech Republic
MEDICAL PLUS s.r.o
🇨🇿Uherske Hradiste, Czech Republic
Radiant Research
🇺🇸Columbus, Ohio, United States