Radiographic and symptomatic knee osteoarthritis in either one or both knees MedDRA version: 21.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859
Conditions
Interventions
Product Code: APPA
Pharmaceutical Form: Capsule
INN or Proposed INN: Paeonol
CAS Number: 552-41-0
Other descriptive name: PAEONOL
Concentration unit: mg milligram(s)
Concentration type: equal
Concentr
Sponsors
AKL Research and Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject is able to read and understand the language and content of the study material, understand the requirements for study visits, and is willing to provide information at the scheduled evaluations and appropriate written informed consent has been obtained. 2. Femorotibial osteoarthritis of the knee, according to the American College of Rheumatology (ACR) clinical and radiographic criteria (Altman et al. 1986) (Appendix A). 3. Radiological OA grade 2 or 3 of the target knee, using the Kellgren-Lawrence method (Kellgren & Lawrence 1957) as graded by central, independent reading of X-ray obtained during screening, or on a recent (within 6 months) X-ray image which fulfills the protocol specifications for reading. 4. Age between 40 years and 85 years at the time of screening, both included; of either sex. 5. Pain score rated on an 11-point numerical rating scale of the target knee of = 20 and = 45 out of 50 in response to the WOMAC pain sub-score (5 questions), at the time of screening and baseline. The subject should have undergone a washout-period of at least 5 half-lives of any analgesic medication before completing the questionnaires. 6. Women of child-bearing potential must use a highly effective method of contraception (Please see Appendix B). Postmenopausal status is defined as being amenorrheic for at least 1 year prior to screening. Sexually active men with a female partner of childbearing potential must ensure that their female partner uses a highly effective method of contraception and agree to use condom from enrolment up to at least 3 months after the study end. Furthermore, male participants must agree not to donate sperm throughout the study and at least 3 months after the study end. 7. Knee pain in the target knee for 14 days of the preceding month (periarticular knee pain due to OA and not due to non-OA conditions such as bursitis, tendonitis, etc.) based on subject report. 8. Inadequate response or intolerance to analgesics and/or non-steroidal anti-inflammatory drugs (NSAIDs) as reported by the subject 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 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. Known or suspected hypersensitivity to or previous hypersensitivity reactions to APPA, or any of the excipients in the investigational product. 2. For women of childbearing potential: a) Pregnancy (i.e. positive pregnancy test at Screening) or breastfeeding b) Failure to agree to practice a highly effective method of contraception (see Appendix B), from enrollment up to at least 3 months after the study end. 3. For sexually active men with a female partner of childbearing potential: Failure to agree to ensure that their female partner uses a highly effective method of contraception, to agree to use condom (see Appendix B) from enrollment up to at least 3 months after the study end, and to agree not to donate sperm throughout the study and at least 3 months after the study end. 4. Intra-articular delivery of corticosteroids within 3 months or hyaluronic acid within 6 months of screening in the target knee or into any other joint within 30 days prior to screening. 5. Systemic corticosteroid treatment of more than 14 days during the past 6 months prior to screening. 6. Major surgery or arthroscopy of the target knee within the previous year prior to screening. 7. Planned surgery on either knee within the next 3 months. 8. Use of a currently unapproved investigational drug, device or biologic within 3 months prior to randomization. 9. Presence of inflammatory arthritis, such as rheumatoid arthritis, psoriatic arthritis, polymyalgia rheumatica, gout or pseudogout with history of clinical attacks. 10. Current malignancy or treatment for malignancy within the past five years, with the exception of treated non-melanoma skin cancer, unless affecting the target knee area, or carcinoma in situ events. 11. Any other abnormal laboratory results or significant medical conditions that the Investigator believes should preclude the subject's participation in the trial. 12. Prior septic arthritis of the target knee. 13. Known osteoarthritis of the hip(s) if pain in either or both hip(s) exceeds that of the target knee using the WOMAC Hip Pain sub-score for that hip at the time of screening 14. Presence of significant radicular back pain, as reported by the subject. 15. Presence of severe pain in either knee, defined as > 45 out of 50 in response to the WOMAC pain sub-score (5 questions), at the time of screening or baseline, regardless of the eligibility of the contralateral knee. 16. Body Mass Index = 40 kg/m2 17. Estimated glomerular filtration rate < 30 mL/min using the Modification of Diet in Renal Disease (MDRD) method. 18. Substantial use of moderate or higher strength opioid medication for the treatment of pain within 4 weeks before the baseline visit, as evaluated by the investigator. 19. Use of duloxetine, pregabalin, or gabapentin within 4 weeks before the baseline visit. 20. History of alcohol or drug abuse within the 5 years prior to randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the change in pain, in terms of the WOMAC pain score of the target knee.;Secondary Objective: • To evaluate changes in symptoms of OA • To evaluate the changes in physical functioning • To evaluate the safety and tolerability of APPA • To evaluate changes in quality of life Exploratory Objectives • To explore biomarkers of joint tissue turnover;Primary end point(s): The primary endpoint of this trial is the change from baseline in WOMAC pain sub-score (sum of questions 1 to 5) of the target knee as evaluated at week 4. ;Timepoint(s) of evaluation of this end point: week 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Changes from baseline in WOMAC total score and the WOMAC function and stiffness scores at week 4 • Changes from baseline in constant, intermittent OA and total pain assessed by ICOAP scores at week 4 • Changes from baseline in WOMAC pain weight-bearing score (questions 1, 2, and 5) and non-weight bearing score (questions 3 and 4) at week 4 • Changes from baseline in gait speed as assessed by the 20 Meter Walk test at week 4 • Change from baseline in the weekly mean of the average daily pain intensity at Week 4 • Area-under-effect curves of the weekly mean of the average daily pain intensity at Week 4 • OMERACT-OARSI responder rate at week 4 • Total dose of rescue medication calculated as the sum of tablets used, based on pill counts • Time between baseline and first use of rescue medication • Changes from baseline in the Patient Global Assessment (PGA) score at week 4 • Changes from baseline in quality of life assessed by the EQ5D at week 4 SAFETY ENDPOINTS • Nature, incidence and severity of AEs • Changes in laboratory safety parameters, vital signs, 12-lead ECG parameters, and weight EXPLORATORY ENDPOINTS • Time to achieve a clinically relevant pain reduction defined as a decrease from baseline of at least 1 points out of 10 in the 11-point average of daily pain score • Time to achieve “moderate improvement” and time to achieve “high improvement” in OMERACT-OARSI response • Changes in serum and urine biomarkers of joint tissue turnover;Timepoint(s) of evaluation of this end point: week 4 | — |
Countries
Denmark
Contacts
Public ContactRegulatory Affairs Department
Nordic Bioscience Clinical Development
Outcome results
None listed