A Phase 1/2a Study to Evaluate Single Intraarticular Injections of 3 Dose Levels of SYN321 and Placebo in Patients With Symptomatic Knee Osteoarthritis

Exclusion Criteria

• •1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the trial, or influence the results or the patient's ability to participate in the trial.
• •2. Previous IA fracture of the knee.
• •3. Patient has rheumatoid arthritis, psoriatic arthritis, or has been diagnosed with any other disorders that is the primary source of their knee pain, including but not limited to: osteonecrosis, radiculopathy, bursitis, tendinitis, tumor, cancer.
• •4. IA injections of steroids or HA or other invasive procedure (e.g., arthroscopy, arthrography, surgery) in the knee within 3 months prior to screening.
• •5. Conditions or medications that could confound the assessment of pain, as judged by the Investigator.
• •6. Conditions that could be adversely affected by an IA injection (e.g., eczema, skin infection, high bleeding risk etc.), as judged by the Investigator.
• •7. Any clinically significant illness (except KOA), medical/surgical procedure, or trauma within 4 weeks of the administration of IMP.
• •8. Malignancy within the past 5 years, with the exception of in situ removal of basal cell carcinoma.
• •9. Any planned major surgery within the duration of the trial.
• •10. Patients who are pregnant, currently breastfeeding, or intend to become pregnant during the course of the trial.
• •11. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibodies and/or human immunodeficiency virus (HIV).
• •12. After 10 minutes supine rest at the time of screening, any vital signs outside the following ranges:
• •* Systolic blood pressure (BP): \<90 or \>160 mmHg, or
• •* Diastolic blood pressure \<50 or \>95 mmHg, or
• •* Pulse \<40 or \>90 bpm
• •13. Prolonged QTcF (\> 450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator.
• •14. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to SYN321, including disinfectants and adhesives or hypersensitivity to acetylsalicylic acid.
• •15. History of asthma, angioedema, urticaria or acute rhinitis induced by NSAID, including acetylsalicylic acid.
• •16. Regular use of any prescribed or non-prescribed medications, including but not limited to antacids, analgesics, herbal remedies, vitamins and minerals, within 10 days prior to the first administration of IMP, as well as nasal decongestants without cortisone, antihistamine, or anticholinergics for a maximum of 10 days, at the discretion of the Investigator.
• •17. Patient has taken pain medication or has received pain medicine other than paracetamol for conditions unrelated to KOA of the index knee within 10 days prior to the injection.
• •18. Planned treatment or treatment with another investigational drug within 3 months prior to Day 1. Patients consented and screened but not dosed in previous phase 1 studies will not be excluded.
• •19. Current smokers or users of nicotine products. Irregular use of nicotine (e.g., smoking, snuffing, chewing tobacco) less than 3 times/week before the screening visit will be allowed.
• •20. Positive screen for drugs of abuse or alcohol at screening. Positive results that are expected given the patient's medical history and prescribed medications can be disregarded as judged by the Investigator.
• •21. History of or current alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
• •22. History of or current drug abuse, as judged by the Investigator.
• •23. History of or current use of anabolic steroids, as judged by the Investigator.
• •24. Plasma donation within 1 month of screening or blood donation (or corresponding blood loss) during the last 3 months prior to screening.
• •25. The Investigator considers the patient unlikely to comply with trial procedures, restrictions, and requirements.