Clinical trial NCT02205814: Fasitibant Intra-articular Injection in Patients With Symptomatic Osteoarthritis of the Knee
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Knee Osteoarthritis
Keywords: Osteoarthritis, Knee
Arthritis
WOMAC
Injections, intra-articular
Fasitibant
MEN 16132
Lead sponsor: Menarini Group
Sponsor class: INDUSTRY
First posted: 2014-07-31
Enrollment: 436
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in WOMAC A
timeFrame: from baseline up to 2 weeks after randomisation
Secondary outcomes:
measure: Change in WOMAC INDEX
timeFrame: from baseline up to 6 weeks after randomisation
measure: Responder Rate According to OMERACT-OARSI Criteria
timeFrame: from baseline up to 6 weeks after randomisation
measure: Euro Quality of Life Questionnaire (EQ-5D-5L) Responder Rate
timeFrame: from baseline up to 6 weeks after randomisation
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Tucson Orthopaedic Institute
state: Arizona
city: Englewood
country: United States
facility: Colorado Orthopaedic Consultants
state: Colorado
city: Deland
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Columbus
country: United States
facility: Radiant Research
state: Ohio
city: Columbus
country: United States
facility: Columbus Clinical Research
state: Ohio
city: Altoona
country: United States
facility: Blair Orthopaedic Associates
state: Pennsylvania
city: Austin
country: United States
facility: Tekton Research
state: Texas
city: Draper
country: United States
facility: Physicians Research Options, LLC
state: Utah
city: Spokane
country: United States
facility: Spokan Joint Replacement Center
state: Washington
city: Brno
country: Czech Republic
facility: Revmatologie s.r.o.
city: Prague
country: Czech Republic
facility: Institute of Rheumatology, Charles University Faculty Hospital
city: Uherske Hradiste
country: Czech Republic
facility: MEDICAL PLUS s.r.o
city: Berlin
country: Germany
facility: Synexus Clinical Research GmbH, Research Centre Berlin
city: Bochum
country: Germany
facility: Synexus Clinical Research GmbH, Research Centre Bochum
city: Frankfurt
country: Germany
facility: Synexus Clinical Research GmbH, Research Centre Frankfurt
city: Hamburg
country: Germany
facility: Clinical Research Hamburg GmbH
city: Leipzig
country: Germany
facility: Synexus Clinical Research GmbH, Research Centre Leipzig
city: Leipzig
country: Germany
facility: AmBeNet GmbH
city: Firenze
country: Italy
facility: Dipartimento di Medicina Interna - SOD di Reumatologia Azienda - Ospedaliero Universitaria Careggi
state: Tuscany
city: Cona
country: Italy
facility: Azienda Ospedaliero-Universitaria S.Anna/ Unità Operativa Complessa e Sezione di Reumatologia/Dipartimento di Medicina Clinica e Sperimentale
city: Lecce
country: Italy
facility: Ospedale Galateo U.O. di Reumatologia
city: Magenta
country: Italy
facility: Ospedale Fornaroli/Unità Complessa di Reumatologia
city: Milano
country: Italy
facility: Ospedale Luigi Sacco, Azienda Ospedaliera, Polo Universitario/Unità Operativa Complessa di Reumatologia
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia/Policlinico di Monteluce/Unità Operativa diagnosi e cura delle malattie reumatiche
city: Verona
country: Italy
facility: Centro Ricerche Cliniche di Verona
Study officials:
affiliation: Institute of Rheumatology, Charles University Faculty Hospital, Na Slupi 4, 128 50 Prague 2, Czech Republic
name: Karel Pavelka, Professor
role: STUDY_CHAIR
References: