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

NCT ID: NCT02205814

Last Updated: 2015-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 436 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2015-01-31

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.

Conditions

Knee Osteoarthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Fasitibant low dose

Drug: solution for intra-articular injection

Group Type: EXPERIMENTAL

Fasitibant- low dose

Intervention Type: DRUG

Single intra-articular injection of low dose of fasitibant

Fasitibant intermediate dose

Drug: solution for intra-articular injection

Group Type: EXPERIMENTAL

Fasitibant- intermediate dose

Intervention Type: DRUG

Single intra-articular injection of intermediate dose of fasitibant

Fasitibant high dose

Drug: solution for intra-articular injection

Group Type: EXPERIMENTAL

Fasitibant- high dose

Intervention Type: DRUG

Single intra-articular injection of high dose of fasitibant

PLACEBO

Drug: solution for intra-articular injection

Group Type: PLACEBO_COMPARATOR

Placebo comparator

Intervention Type: DRUG

Single intra-articular injection of placebo

Interventions

Fasitibant- low dose

Single intra-articular injection of low dose of fasitibant

Intervention Type: DRUG

Fasitibant- intermediate dose

Single intra-articular injection of intermediate dose of fasitibant

Intervention Type: DRUG

Fasitibant- high dose

Single intra-articular injection of high dose of fasitibant

Intervention Type: DRUG

Placebo comparator

Single intra-articular injection of placebo

Intervention Type: DRUG

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Menarini Group

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karel Pavelka, Professor

Role: STUDY_CHAIR

Institute of Rheumatology, Charles University Faculty Hospital, Na Slupi 4, 128 50 Prague 2, Czech Republic

Locations

Tucson Orthopaedic Institute

Tucson, Arizona, United States

Colorado Orthopaedic Consultants

Englewood, Colorado, United States

Avail Clinical Research, LLC

DeLand, Florida, United States

Radiant Research

Columbus, Ohio, United States

Columbus Clinical Research

Columbus, Ohio, United States

Blair Orthopaedic Associates

Altoona, Pennsylvania, United States

Tekton Research

Austin, Texas, United States

Physicians Research Options, LLC

Draper, Utah, United States

Spokan Joint Replacement Center

Spokane, Washington, United States

Revmatologie s.r.o.

Brno, , Czechia

Institute of Rheumatology, Charles University Faculty Hospital

Prague, , Czechia

MEDICAL PLUS s.r.o

Uherské Hradiště, , Czechia

Synexus Clinical Research GmbH, Research Centre Berlin

Berlin, , Germany

Synexus Clinical Research GmbH, Research Centre Bochum

Bochum, , Germany

Synexus Clinical Research GmbH, Research Centre Frankfurt

Frankfurt, , Germany

Clinical Research Hamburg GmbH

Hamburg, , Germany

Synexus Clinical Research GmbH, Research Centre Leipzig

Leipzig, , Germany

AmBeNet GmbH

Leipzig, , Germany

Dipartimento di Medicina Interna - SOD di Reumatologia Azienda - Ospedaliero Universitaria Careggi

Florence, Tuscany, Italy

Azienda Ospedaliero-Universitaria S.Anna/ Unità Operativa Complessa e Sezione di Reumatologia/Dipartimento di Medicina Clinica e Sperimentale

Cona, , 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

Milan, , Italy

Azienda Ospedaliera di Perugia/Policlinico di Monteluce/Unità Operativa diagnosi e cura delle malattie reumatiche

Perugia, , Italy

Centro Ricerche Cliniche di Verona

Verona, , Italy

Countries

United States; Czechia; Germany; Italy

Other Identifiers

2013-004999-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BKOS-04

Identifier Type: -

Identifier Source: org_study_id