Osteoarthritis of the knee MedDRA version: 18.0 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859
Conditions
Interventions
Product Name: FX006 40mg vial
Product Code: FX600
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: TRIAMCINOLONE ACETONIDE
Current Sponsor code: FX006
Concentration unit:
Sponsors
Flexion Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written consent to participate in the study 2. Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions 3. Male or female =40 years of age 4. Symptoms associated with OA of the knee for = 6 months prior to Screening (patient reported is acceptable) 5. Currently meets American College of Rheumatology (ACR) Criteria (clinical and radiological) for OA (Altman et al, 1986) as follows: • Knee pain • at least 1 of the following: o Age > 50 years o Stiffness 15 days over the last month (as reported by the patient) 8. Mean score of = 5 and = 9 on the 24-hr average pain score (0-10 numeric ratings scale (NRS)) using the average daily ratings for at least 5 of the 7 days prior to Day 1 9. No more than one 24-hr average pain score (0-10 NRS) reported as “10” during the 7 days prior to Day 1 10. If bilateral OA exists, pain in the contralateral knee must be less than pain in the index knee as reported by the patient 11. Body mass index (BMI) = 40 kg/m2 12. Ambulatory and in good general health 13. Willingness to abstain from use of protocol-specified restricted medications and non-pharmacological therapies during the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 300
Exclusion criteria
Exclusion criteria: Patients fulfilling at least one of the following criteria may not be included in the study: Disease-related criteria 1. Any condition that could possibly confound the patient’s assessment of index knee pain in judgment of the investigator (i.e., ipsilateral hip OA, gout, radicular low back pain and hip pain that is referred to the knee that could cause misclassification, pain in any other area of the lower extremities or back that is equal to or greater than the index knee pain) 2. Fibromyalgia, Reiter’s syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease 3. History of infection in the index knee 4. Clinical signs and symptoms of active knee infection or crystal disease of the index knee within 1 month of Screening 5. Unstable joint (such as a torn anterior cruciate ligament) within 12 months of Screening Previous or concomitant OA treatment-related criteria 6. IA corticosteroid (investigational or marketed) in any joint within 3 months of Screening 7. IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening 8. Intramuscular (IM) or oral corticosteroids (investigational or marketed) within 1 month of Screening 9. Any other IA investigational drug/biologic use within 6 months of Screening 10. Prior use of FX006 11. Prior arthroscopic or open surgery of the index knee within 12 months of Screening 12. Planned/anticipated surgery of the index knee or any other surgery that would require use of a restricted medication during the study period Patient-related criteria 13. Known hypersensitivity to any form of triamcinolone 14. History of sarcoidosis or amyloidosis 15. Active or history of malignancy within the last 5 years, with the exception of resected basal cell carcinoma, squamous cell carcinoma of the skin, or effectively managed cervical carcinoma 16. Known active or quiescent systemic fungal, bacterial (including tuberculosis), viral or parasitic infections, or ocular herpes simplex 17. Any infection requiring intravenous antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening 18. History of osteomyelitis 19. Known or clinically suspected infection with human immunodeficiency virus (HIV), hepatitis B or C viruses 20. Any clinically significant electrocardiogram (ECG) abnormality as judged by the Investigator 21. Patients requiring or likely to require chronic treatment with corticosteroids during the study period based on patient medical history 22. Uncontrolled diabetes as indicated by a hemoglobin A1c (HbA1c) of > 7.5% (> 59 mmol/mol) 23. Active psychiatric disorder including psychosis (e.g., schizophrenia), bipolar disorder, uncontrolled anxiety disorder and major depressive disorder 24. History of or active Cushing’s syndrome 25. Positive drug screen (amphetamines, barbiturates, benzodiazepines (indicated as a muscle relaxant), cocaine, opiates, tetrahydrocannabinol (THC)) 26. Active substance abuse (drugs or alcohol), history of chronic substance abuse within the past year, or prior chronic substance abuse judged by the investigator as likely to recur during the study 27. Skin breakdown at the knee where the injection would take place 28. Women who are pregnant or nursing 29. Women of child-bearing potential (not surgically sterile or post-menopausal for at least 1 year as documented in medical history) not using a highly effective method of contraception (abstinence; oral, inje
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the magnitude and duration of pain relief of a single intra-articular (IA) injection of FX006, an extended release formulation of triamcinolone acetonide (TCA), relative to normal saline (placebo control).;Secondary Objective: - To assess the effect of FX006 on the magnitude and duration of pain relief relative to triamcinolone acetonide injectable suspension, immediate release (commercially available) (TCA IR). - To assess the effect of FX006 on function, responder status, global impressions of change, stiffness, and consumption of analgesic medications relative to both controls. - To assess the safety and general tolerability of a single IA injection of FX006 relative to both controls.;Primary end point(s): Efficacy Average daily (24-h) pain intensity score on a 0 to 10 NRS scale with 0 indicating ‘no pain’ and 10 indicating ‘pain as bad as you can imagine’ (Dworkin et al¸ 2005; Cleeland and Ryan, 1994);Timepoint(s) of evaluation of this end point: The study will involve a Screening period (up to 21 days) and 7 out-patient visits (Days 1 [Baseline], Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24). Each patient will be evaluated for a total of 24 weeks after treatment. Patients will be evaluated for efficacy and safety. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy Worst daily pain intensity score on a 0 to 10 NRS scale with 0 indicating ‘no pain’ and 10 indicating ‘pain as bad as you can imagine’ (Dworkin et al¸ 2005) • WOMAC? Osteoarthritis Index (LK 3.1, 5-point scale): pain, stiffness and function domains independently and collectively (Bellamy et al, 1988). • PGIC: 7-point scale (Farrar et al, 2001; Guy, 1976; Dworkin et al, 2005) (Appendix 3). • CGIC: 7-point scale (Guy, 1976) (Appendix 3). • KOOS Quality of Life (QOL) Subscale (http://www.koos.nu/) • SF-12 (1 week recall version) (http://www.sf-36.org/tools/sf12.shtml) • Responder status as defined by: o Proportion of patients experiencing either >50%, >30% or >20% decrease (improvement) in pain from baseline in weekly mean of the average daily (24-hr) pain intensity scores (substantial, at least moderate and minimum clinically important difference, respectively, as defined by Dworkin et al, 2008) o Outcome Measures in Rheumatology (OMERACT) - Osteoarthritis Research Society International (OARSI) criteria (Pham, 2004) • Time of onset of pain relief (based on average daily pain intensity scores) • Consumption of rescue medication Safety • AEs • Physical examinations • Index knee examinations • Index knee X-rays • Vital signs • ECGs • Clinical laboratory evaluations;Timepoint(s) of evaluation of this end point: The study will involve a Screening period (up to 21 days) and 7 out-patient visits (Days 1 [Baseline], Week 4, Week 8, Week 12, Week 16, Week 20 and Week 24). Each patient will be evaluated for a total of 24 weeks after treatment. Patients will be evaluated for efficacy and safety. | — |
Countries
Australia, Denmark, Estonia, Hong Kong, Lithuania, New Zealand, Romania, United States
Contacts
Public ContactClinical Research
Flexion Therapeutics
Outcome results
None listed