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

Knee Osteoarthritis Clinical Trial

— ALBATROSS-3  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02205814
• Other study ID #: BKOS-04
• Secondary ID: 2013-004999-35
• Status: Completed
• Phase: Phase 2
• First received: July 14, 2014
• Last updated: October 2, 2015
• Start date: April 2014
• Est. completion date: January 2015

Study information

• Verified date: October 2015
• Source: Menarini Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationItaly: The Italian Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesCzech Republic: State Institute for Drug Control
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 436
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Fasitibant- low dose
Single intra-articular injection of low dose of fasitibant
• Fasitibant- intermediate dose
Single intra-articular injection of intermediate dose of fasitibant
• Fasitibant- high dose
Single intra-articular injection of high dose of fasitibant
• Placebo comparator
Single intra-articular injection of placebo

Locations

Country	Name	City	State
Czech Republic	Revmatologie s.r.o.	Brno
Czech Republic	Institute of Rheumatology, Charles University Faculty Hospital	Prague
Czech Republic	MEDICAL PLUS s.r.o	Uherske Hradiste
Germany	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	AmBeNet GmbH	Leipzig
Germany	Synexus Clinical Research GmbH, Research Centre Leipzig	Leipzig
Italy	Azienda Ospedaliero-Universitaria S.Anna/ Unità Operativa Complessa e Sezione di Reumatologia/Dipartimento di Medicina Clinica e Sperimentale	Cona
Italy	Dipartimento di Medicina Interna - SOD di Reumatologia Azienda - Ospedaliero Universitaria Careggi	Firenze	Tuscany
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	Azienda Ospedaliera di Perugia/Policlinico di Monteluce/Unità Operativa diagnosi e cura delle malattie reumatiche	Perugia
Italy	Centro Ricerche Cliniche di Verona	Verona
United States	Blair Orthopaedic Associates	Altoona	Pennsylvania
United States	Tekton Research	Austin	Texas
United States	Columbus Clinical Research	Columbus	Ohio
United States	Radiant Research	Columbus	Ohio
United States	Avail Clinical Research, LLC	Deland	Florida
United States	Physicians Research Options, LLC	Draper	Utah
United States	Colorado Orthopaedic Consultants	Englewood	Colorado
United States	Spokan Joint Replacement Center	Spokane	Washington
United States	Tucson Orthopaedic Institute	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Menarini Group

Countries where clinical trial is conducted

United States,  Czech Republic,  Germany,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No