Fasitibant Intra-articular Injection in Patients With Symptomatic Osteoarthritis of the Knee (ALBATROSS-3)

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.

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.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: Fasitibant- low dose; Drug: Fasitibant- intermediate dose; Drug: Fasitibant- high dose; Drug: Placebo comparator

• Study Type: Interventional
• Enrollment (Actual): 436
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czech Republic
  • Brno, Czech Republic, 638 00
    • Revmatologie s.r.o.
  • Prague, Czech Republic, 128 50
    • Institute of Rheumatology, Charles University Faculty Hospital
  • Uherske Hradiste, Czech Republic, 686 01
    • MEDICAL PLUS s.r.o
• Germany
  • Berlin, Germany, 1262
    • Synexus Clinical Research GmbH, Research Centre Berlin
  • Bochum, Germany, 44787
    • Synexus Clinical Research GmbH, Research Centre Bochum
  • Frankfurt, Germany, 60596
    • Synexus Clinical Research GmbH, Research Centre Frankfurt
  • Hamburg, Germany, 22143
    • Clinical Research Hamburg GmbH
  • Leipzig, Germany, 04103
    • Synexus Clinical Research GmbH, Research Centre Leipzig
  • Leipzig, Germany, 04107
    • AmBeNet GmbH
• Italy
  • Cona, Italy, 44124
    • Azienda Ospedaliero-Universitaria S.Anna/ Unità Operativa Complessa e Sezione di Reumatologia/Dipartimento di Medicina Clinica e Sperimentale
  • Lecce, Italy, 73016
    • Ospedale Galateo U.O. di Reumatologia
  • Magenta, Italy, 20013
    • Ospedale Fornaroli/Unità Complessa di Reumatologia
  • Milano, Italy, 20157
    • Ospedale Luigi Sacco, Azienda Ospedaliera, Polo Universitario/Unità Operativa Complessa di Reumatologia
  • Perugia, Italy, 06122
    • Azienda Ospedaliera di Perugia/Policlinico di Monteluce/Unità Operativa diagnosi e cura delle malattie reumatiche
  • Verona, Italy, 37134
    • Centro Ricerche Cliniche Di Verona
  • Tuscany
    • Firenze, Tuscany, Italy, 50139
      • Dipartimento di Medicina Interna - SOD di Reumatologia Azienda - Ospedaliero Universitaria Careggi
• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Tucson Orthopaedic Institute
  • Colorado
    • Englewood, Colorado, United States, 80110
      • Colorado Orthopaedic Consultants
  • Florida
    • Deland, Florida, United States, 32720
      • Avail Clinical Research, LLC
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Columbus Clinical Research
    • Columbus, Ohio, United States, 43212
      • Radiant Research
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Blair Orthopaedic Associates
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research
  • Utah
    • Draper, Utah, United States, 84020
      • Physicians Research Options, LLC
  • Washington
    • Spokane, Washington, United States, 99218
      • Spokan Joint Replacement Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Menarini Group
• Investigators: Study Chair: Karel Pavelka, Professor, Institute of Rheumatology, Charles University Faculty Hospital, Na Slupi 4, 128 50 Prague 2, Czech Republic

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: July 14, 2014
• First Submitted That Met QC Criteria: July 30, 2014
• First Posted (Estimate): July 31, 2014

Study Record Updates

• Last Update Posted (Estimate): November 3, 2015
• Last Update Submitted That Met QC Criteria: October 2, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Arthritis; WOMAC; Osteoarthritis, Knee; Injections, intra-articular; Fasitibant; MEN 16132
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Bradykinin B2 Receptor Antagonists; Bradykinin Receptor Antagonists; (4-amino-5-(4-(4-(2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido)tetrahydro-2H-4-pyranoylcarbonyl)piperazino)-5-oxopentyl)(trimethyl)ammonium
• Other Study ID Numbers: BKOS-04; 2013-004999-35 (EudraCT Number)