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A placebo-controlled, double-blinded, randomized, dose-finding trial using a combination of apocynin and paeonol (APPA) for the treatment of knee osteoarthritis

Phase 1
Recruiting
Conditions
Knee osteoarthritis
MedDRA version: 21.1Level: LLTClassification code: 10023476Term: Knee osteoarthritis Class: 10028395
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
Registration Number
CTIS2023-508791-11-00
Lead Sponsor
Akl Research & Development Limited
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
All
Target Recruitment
225
Inclusion Criteria

The participant is able to read and understand the language and content of the study material, understand and comply with the requirements of the study, and is willing to provide information at the scheduled evaluations and appropriate written informed consent has been obtained., Age between 40 years and 85 years at the time of screening (inclusive) of either sex., Femorotibial osteoarthritis of the knee, according to the American College of Rheumatology (ACR) clinical and radiographic criteria (Appendix I)., 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 a Fixed-Flexion X-ray obtained during screening, or on a recent (within 6 months) X-ray image which fulfills the protocol specifications for reading., Screening and baseline target knee WOMAC pain sub-score (5 questions) = 25 and < 45 out of 50., PainDETECT = 13out of 38 at screening, Failure in response or intolerance of at least one OA therapy (e.g. physiotherapy, paracetamol, local or systemic NSAID, short term opioid use, injections of hyaluronic acid, or corticosteroids) in the opinion of the investigator.

Exclusion Criteria

Known or suspected hypersensitivity to or previous hypersensitivity reactions to APPA, or any of the excipients in the investigational product., Current malignancy or treatment for malignancy within the past five years, apart from resected basal cell carcinoma, squamous skin cell carcinoma, or resected cervical atypia or carcinoma in situ, unless affecting the target knee area., Any other abnormal laboratory results or significant medical conditions that the Investigator believes should preclude participation in the trial., Prior septic arthritis of the target knee., Known OA of the hip(s) if pain in either or both hip(s) exceeds that of the target knee on the WOMAC Hip Pain sub-score at the time of screening., Active comorbid condition other than OA (e.g radicular back pain, bursitis, tendinitis) significantly affecting target knee pain reporting in the opinion of the investigator., Body Mass Index = 40 kg/m2, Estimated glomerular filtration rate < 30 mL/min using the Modification of Diet in Renal Disease (MDRD) method., Substantial use of moderate or higher strength opioid medication within 6 weeks before the screening visit, as evaluated by the investigator., Use of serotonin–norepinephrine reuptake inhibitors (i.e duloxetine), pregabalin, or gabapentin within 4 weeks before the screening visit., History of alcohol or drug abuse within the 5 years prior to randomization, in the opinion of the investigator., For women of childbearing potential: a. Pregnancy (i.e. positive serum pregnancy test at screening) or breastfeeding b. Failure to agree to practice a highly effective method of contraception (see Appendix II), from enrolment up to at least 3 months after the study end., For sexually active men with a female partner of childbearing potential: a. Failure to agree to ensure that their female partners use a highly effective method of contraception (see Appendix II) from enrolment up to at least 3 months after the study end. b. Failure to agree not to donate sperm throughout the study and at least 3 months after the study end., Intra-articular injection of corticosteroids within 3 months or hyaluronic acid within 6 months of screening in the target knee or into any other major joint within 30 days prior to screening (for extended-release corticosteroid injections: within 6 months in target knee and 3 months into any other major joint)., Systemic corticosteroid treatment for the treatment of musculoskeletal conditions of more than 14 days during the past 6 months prior to screening., Target knee major surgery or arthroscopy within the year prior to screening., Planned surgery on either knee within the next 6 months., Use of a currently unapproved investigational drug, device, or biologic within 3 months prior to randomization., Presence of inflammatory arthritis, such as rheumatoid arthritis, psoriatic arthritis, polymyalgia rheumatica, gout or pseudogout with significant history of clinical attacks (in the opinion of the investigator), or presence of connective tissue disease.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
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