Symptomatic osteoarthritis (OA) of the knee. MedDRA version: 17.0 Level: SOC Classification code 10028395 Term: Musculoskeletal and connective tissue disorders System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: Fasitibant chloride bis-hydrochloride
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Fasitibant chloride (as bis hydrochloride)
CAS Number: 883969
Sponsors
Menarini Ricerche S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Properly executed written informed consent. 2.Male or female patients 40-80 years old and with a BMI = 200 mm and = 40 mm and =65 years) yes F.1.3.1 Number of subjects for this age range 220
Exclusion criteria
Exclusion criteria: 1.Inability to personally provide written informed consent (e.g. patients with psychiatric illness). 2.Inability to understand or collaborate with study procedures and requirements, including answering to the study questionnaire/symptoms reporting. 3.Patients who participated in another clinical trial within 30 days (90 days in case of OA trial) prior to screening. 4.Patients with Kellgren Lawrence Grade 1 or Grade 4 OA of the knee. 5.Knee condition representing on Investigator’s judgment an indication for surgery (e.g. significant axial deviation, severe medio-lateral and/or anterior-posterior instability, severe bone/joint deformity). 6.OA secondary to inflammatory/autoimmune forms of arthritis, septic arthritis, or genetic diseases, which have a distinct impact on the outcome. 7.Patients with acute fractures, severe loss of bone density, history of aseptic necrosis, isolated patella-femoral syndrome (i.e. chondromalacia), or joint replacement in the affected knee. 8.Patients with OA predominant in the lateral compartment, or any significant valgus deformity. 9.Patients who -as per Investigator’s judgment- have any clinically significant or unstable disease or condition interfering with the evaluation of the safety and efficacy of study treatment along the study period (e.g. clinically significant and unstable cardiovascular or respiratory diseases, congenital defects, spinal OA). 10.History of symptomatic severe hip OA and painful hip prosthesis. 11.Major injury (including ligament sprains or muscle/tendon strains > grade 2 and meniscal tears > grade 2) or major surgery to the index knee. 12.Any pain > 30 mm on a 100 mm visual analogue scale (VAS) that could interfere with the assessment of the index knee pain (e.g. local or radiating pain in any part of the lower extremities). 13.Clinically significant venous or lymphatic stasis in the relevant limb. 14.Acupuncture and physiotherapy in the last 4 weeks prior to randomisation, or likely to start during the course of the study. 15.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. 16.Use of systemic or topical corticosteroids > 10 mg prednisolone equivalent per day, or immunosuppressant drugs during 30 days prior to randomisation, or likely to be used during the course of the study. 17.Use of any pain or OA medication (e.g. NSAIDs, COX-2 inhibitors, analgesics, antidepressive agents), including topical treatments, within a minimum of 5 times their half life prior to randomisation and during the course of the study. 18.Viscosupplementation (intra-articular injection of hyaluronic acid) to the target knee administered < 4 months prior to randomisation and/or scheduled during the course of the study. Safety-related exclusion criteria 19.History of hypersensitivity/allergy to drugs including paracetamol and to disinfectants (antimicrobial soaps and /or povidone-iodine solution). 20. Use of any medications that are substrate of CYP3A4 and/or moderate or strong CYP3A4 inhibitors during the 4 weeks prior to Randomisation and the overall study duration. 21.Patients with any of the following: a)clinically relevant cardiovascular, pulmonary, gastro-intestinal, haematological, neurologic, psychiatric or infectious diseases, or unstable metabolic diseases, or malignant neoplasms that, in the opinion of the Investigator, may pose the patient at risk, or c
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate fasitibant, given as single IA injection at three different doses versus placebo, as an efficacious symptom modifying treatment of knee OA.;Secondary Objective: 1.To assess the dose-effect relationship of fasitibant to support the choice of the dose to be studied in a subsequent clinical phase III study. 2.To evaluate the safety and tolerability of single IA fasitibant doses of 1 mg, 2.5 mg and 5 mg as 1 mL solution to patients with symptomatic knee OA. 3.To evaluate fasitibant population pharmacokinetics (pop-PK) in patients with symptomatic OA of the knee and the exposure-response relationship (PK/PD). ;Primary end point(s): The Primary Efficacy Endpoint is the change of the WOMAC VA 3.1 A (total pain) subscore from baseline (Visit 2) over 2 weeks after randomisation.;Timepoint(s) of evaluation of this end point: from randomization (T0) over 2 weeks after randomization | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Clinical Efficacy of study treatments (until 6 weeks): Assessment of OA symptoms (pain, walking pain, stiffness, function) using validated standard questionnaires (WOMAC 3.1 VAS). Assessment of pain at rest and after 15 meters walk. Patients' global assessment of efficacy. Patient’ evaluation of quality of life. Use of Rescue Medication. Exploratory efficacy endpoints The changes from baseline (visit 2) over 12 weeks after randomisation and at 12 week of: Assessment of OA symptoms (pain, walking pain, stiffness, function) using validated standard questionnaires (WOMAC 3.1 VAS). Assessment of pain at rest and after 15 meters walk. Patients' global assessment of efficacy. Patient’ evaluation of quality of life. Safety and tolerability of study treatments: Changes in vital signs (blood pressure, pulse rate, respiratory rate, body temperature; 12-lead electrocardiogram (ECG) parameters; laboratory safety battery tests, and physical examination. Incidence and severity of adverse events. Local tolerability of study medication. Pharmacokinetics of the study treatments in terms of absorption, distribution, metabolism and elimination of the study treatments, including analysis of dose proportionality. ;Timepoint(s) of evaluation of this end point: Clinical Efficacy: Between time of dosing (T0), 1 week (+/-1 days), 2 weeks (+/-1 days), 4 weeks (+/-1 days) and 6 weeks (+/-2 days) after treatment administration. Exploratory efficacy: Between time of dosing (T0) over 12 weeks and at 12 week. Pharmacokinetics: Between time of dosing (T0) and defined time points until 4 weeks (+/-21 days) after treatment administration Safety and tolerability of study treatments: Between time of dosing (T0), over 6 weeks (+/-2 days) after treatment administration. | — |
Countries
Germany, Italy, United States
Contacts
Public ContactProject Management Department
CROMSOURCE srl
Outcome results
None listed