Knee osteoarthritis MedDRA version: 21.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859
Conditions
Interventions
Product Name: SYN321
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Diclofenac ethoxyethylamino succinyl hyaluronan (DEASHA)
Other descriptive name: SYN321
Concentration unit: mg mil
Sponsors
Synartro AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to give written informed consent for participation in the study and willing and able to participate in all procedures and follow-up evaluations necessary to complete the study. 2. Male or female patient clinically diagnosed with KOA, no later than 3 months prior to Visit 1. The KOA diagnosis should be confirmed in the patient’s medical record. 3. Dominant pain in one knee due to KOA with weight bearing pain between 4 and 8 inclusive on the NRS scale (0-10) at the time of inclusion (checked at screening [Visit 1] and confirmed at Visit 2, pain during the last 7 days). 4. Age 40 to 79 years, inclusive at the time of Visit 1. 5. BMI = 18.5 and 25 IU/L is confirmatory). Male patients must be willing to use condom or be vasectomized or practice sexual abstinence from heterosexual intercourse (only allowed when this is the preferred and usual lifestyle of the patient) to prevent pregnancy and drug exposure of a partner and refrain from donating sperm from the first administration of IMP until 3 months after the last administration of IMP. Any female partner of a non-vasectomized male patient who is of child-bearing potenti
Exclusion criteria
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 study, or influence the results or the patient’s ability to participate in the study. 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 study. 10. Patients who are pregnant, currently breastfeeding, or intend to become pregnant during the course of the study. 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): 160 mmHg, or - Diastolic blood pressure 95 mmHg, or - Pulse 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. For intake of allowed medications and rescue medication and others, refer to Section 9.6.2.2 and 9.6.2.3 in the clinical study protocol. 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 patie
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of SYN321 after single IA injection in patients with symptomatic KOA. Three (3) dose levels of SYN321 will be evaluated: 33, 65 mg and 98 mg in volumes of 1.5, 3 and 4.5 mL.;Secondary Objective: - To determine the systemic exposure of diclofenac, linker (and linker associated metabolites), and diclofenac lactam (break down products from SYN321). - To assess the preliminary efficacy following single IA injections of SYN321 at 3 dose levels in patients with symptomatic KOA.;Primary end point(s): - Frequency, seriousness, and intensity of AEs. - Clinically significant changes in electrocardiogram (ECG), vital signs, safety laboratory measurements (hematology, clinical chemistry, coagulation), physical examination findings and local tolerability.;Timepoint(s) of evaluation of this end point: According to study flowchart. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Concentration of diclofenac, linker (and linker associated metabolites) and diclofenac lactam in plasma and urine. The following pharmacokinetic (PK) parameters will be explored: maximum plasma concentration (Cmax) and area under the plasma concentration vs. time curve (AUC) Additional PK parameters may be explored if deemed appropriate. - Self-registered pain using the NRS (0-10) once daily every day until Day 56. NRS sum of pain intensity difference (SPID) for current pain in the index knee will be analyzed for all time points measured. - Self-registered function and quality of life using Knee Injury and Osteoarthritis Outcome Score (KOOS). Change from baseline in average sum of KOOS scores, KOOS subscale scores. - Use of rescue medication.;Timepoint(s) of evaluation of this end point: According to study flowchart. | — |
Countries
Sweden
Contacts
Public ContactHead of Clinical Development
Synartro AB
Outcome results
None listed