Fasitibant Intra-articular Injection in Patients With Symptomatic Osteoarthritis of the Knee
Condition: Knee Osteoarthritis
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Intervention: Fasitibant- low dose; Fasitibant- intermediate dose; Fasitibant- high dose; Placebo comparator
Intervention description: Single intra-articular injection of low dose of fasitibant; Single intra-articular injection of intermediate dose of fasitibant; Single intra-articular injection of high dose of fasitibant; Single intra-articular injection of placebo
Intervention MeSH terms: (4-amino-5-(4-(4-(2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido)tetrahydro-2H-4-pyranoylcarbonyl)piperazino)-5-oxopentyl)(trimethyl)ammonium
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 436.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Osteoarthritis, Knee; Arthritis; WOMAC; Injections, intra-articular; Fasitibant; MEN 16132

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