Status and phase
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Treatments
About
This study aims to understand the safety, drug concentration and distribution of an intra-articular injectable formulation of celecoxib, AVD275, in patients with knee osteoarthritis. One single injection at three different doses of the drug will be studied in a sequential order, and each participant will be monitored for 24 weeks over ten clinical visits.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Written consent to participate in the study; Willingness and ability to comply with the study procedures, visit schedules and follow verbal and written instructions
Male or female: 20 years to 75 years of age
Symptoms associated with OA of the knee for ≥6 months prior to screening (patient reported is acceptable); Knee OA may be unilateral or bilateral
Currently meets ACR Criteria (clinical and radiological) for OA as follows:
Knee pain
At least one of the following:
Osteophytes
Kellgren-Lawrence (K-L) Grade 1-4 in the index knee based on X-ray performed during screening (locally read) within 6 months from screening
Body mass index (BMI) ≤ 40 kg/m2
Ambulatory and in good general health
Exclusion criteria
Any condition that could confound the patient's assessment of index knee pain in judgement of the investigator (for example, peri-articular pain of any cause or secondary arthritis that involves the index knee, joint dysplasia, aseptic osteonecrosis, acromegaly, Paget's disease, Ehlers-Danlos Syndrome, Gaucher's disease, Stickler's syndrome, hemophilia, hemochromatosis, or neuropathic arthropathy, radicular lower back pain and hip pain that is referred to the knee that could cause misclassification); Other chronic pain anywhere in the body that confounds assessment of knee or that requires the use of celecoxib
Malalignment of greater than 10 degrees in the femorotibial axis of the index knee on standing; Unstable joint (such as tornanterior cruciate ligament) or traumatic knee injury to the index knee (such as meniscal root tear) within 12 months of screening
Fibromyalgia, Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, reactive arthritis, arthritis associated with inflammatory bowel disease, crystal disease of the index knee (e.g. gout or calcium pyrophosphate deposition disease), rapidly progressive osteoarthritis (defined as joint space narrowing > 1.2 mm/year), sarcoidosis or amyloidosis
Effusion at screening that likely requires joint aspiration for symptom relief from day 2 to day 83 during the study, as indicated by at least four joint drainages in the past year
Intra-articular corticosteroids or intra-articular nonsteroidal antiinflammatory drugs (NSAIDs) (investigational or marketed) in the index knee within 2 months of screening; Intra-articular hyaluronic acid (investigational or marketed) in the index knee within 3 months of screening; Intra-articular Zilretta within 3 months of screening
Intramuscular or oral corticosteroids within 1 month of screening
Patients who received opioids (excluding tramadol and tapentadol) within 2 weeks of screening
Any other investigational drug/biologic use within 3 months of screening
Prior diagnostic arthroscopy to the index knee within 3 months of screening; Prior arthroscopic or open surgery of the index knee (including microfracture and meniscectomy) within 6 months of screening；Prior regenerative joint procedures on the index knee, including, but not limited to, stem cells transplantation, autologous chondrocyte transplantation, or mosaicplasty within 12 months of screening; History of total or partial knee arthroplasty in the index knee
Planned/anticipated surgery of the index knee, any other surgery, or hospitalization during the study period
Known hypersensitivity to any form of NSAIDs (including celecoxib), sulfonamide-containing drugs, carboxymethyl cellulose, polysorbate 80 or lidocaine; History of severe allergic reactions
Active or history of malignancy within the past 3 years, with the exception of resected basal cell carcinoma, squamous cell carcinoma of the knee, or effectively managed cervical carcinoma
Known active or quiescent systemic fungal, bacterial (including tuberculosis), viral or parasitic infections (including HIV, hepatitis B or C viruses), or ocular herpes simplex; Any infection requiring intravenous antibiotics within 2 months of screening or oral antibiotics within 2 weeks of screening; History of infection in the index knee within 12 months of screening; History of osteomyelitis
Any clinically significant laboratory parameters or ECG abnormality as judged by the investigator
Uncontrolled diabetes as indicated by a hemoglobin A1c of >7.5% at screening
History of atherosclerotic cardiovascular disease (ASCVD) defined as prior myocardial infarction, stroke (ischaemic or haemorrhagic), transient ischemic attack, coronary revascularization (e.g., PCI, CABG), peripheral artery disease, or heart failure (NYHA Class II or higher) in the past three years;
Abnormal liver function with AST or ALT > 2 upper limit of normal (ULN) at screening
Abnormal kidney function with eGFR < 45 mL/min/1.73m2 at screening
Platelet count outside normal range at screening
WBC count < 3500 cells/mm3 or >20000 cells/mm3 at screening
Active uncontrolled psychiatric disorder including psychosis (e.g. schizophrenia), bipolar disorder, uncontrolled anxiety disorder and major depressive disorder
Positive drug screen (opiates, amphetamines, cocaine metabolites, benzodiazepines, cannabinoids); 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
Skin breakdown at the knee where the injection would take place; Any skin condition and/or tattoo that may interfere with the evaluation of safety at the injection site
Women who are pregnant or nursing; 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, injected or implanted hormonal methods of contraception; intrauterine device or intrauterine system; condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/cream/suppository; or male sterilization (vasectomy for at least 3 months))
Any other clinically significant acute or chronic medical conditions (e.g. bleeding disorder) that, in the judgement of the investigator, would preclude the use of an intra-articular NSAID or that could compromise patient safety, limit the patient's ability to complete the study, and/or compromise the objectives of the study.
Primary purpose
Allocation
Interventional model
Masking
15 participants in 3 patient groups
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Central trial contact
Ang Li
Data sourced from clinicaltrials.gov
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