Inclusion Criteria:  Individuals between 45 and 80 years of age (inclusive) at the time of the Screening Visit. Willing to use a mobile smart device during the study period. Individuals who do not have access to a mobile device will be provided with one for the duration of the study and trained in its use. Can understand the nature of the study and protocol requirements and is willing to comply with study drug administration requirements and discontinue prohibited concomitant medications. Provides written informed consent to participate in the study using a form approved by the institutional review board (IRB). Is capable of communicating with the site personnel, able to complete subject-reported outcome measures and can be reliably rated on assessment scales (in the opinion of the Site Investigator). Radiography of both knees with a posterior-anterior, fixed-flexion view taken during the Screening visit. The Index knee must show evidence of chronic OA with a K-L Grading Scale of 2 or 3. Such evidence will be provided by a central reading of the radiography of both knees from an expert radiologist of the CCC of EPPIC-Net. Moderate to severe pain in the Index knee associated with OA and stable for a minimum of 6 months prior to Screening in the opinion of the investigator. Confirmation of OA of the index knee: American College of Rheumatology (ACR) diagnostic criteria.  Subjects must have failed 2 or more prior therapies. Failure is deemed to be inadequate relief in the opinion of the investigator. A therapy may be deemed to have been inadequate because of one or more of the following:  unacceptable adverse events (AEs);  inadequate response, or loss of response for chronic OA knee pain or  pain in the index knee was minimally improved, not improved, or was worse and/or function, and/or stiffness in the index knee was minimally improved, not improved, or was worse  medical condition resulting in contraindication to the standard of care appropriate to the severity of the index knee OA pain. "Therapies" include, but are not limited to, each of the following:  nonsteroidal anti-inflammatory drugs (NSAIDs) (including topical), opioids, duloxetine, other systemic therapy, IA corticosteroids, IA viscosupplements physical therapy or bracing. A mid-to-high level summed pain score (0-50) for the Index knee on the WOMAC-A pain subscale, which will be completed by the subject every 3 days (+/-1 day window) during the 14-day Screening period (5 times - screening days 0, 3, 6, 9, 12). An independent interview by an MGH CTNI rater must confirm that the WOMAC-A pain subscale score meets this criterion. Body mass index (BMI) of ≤ 37 kg/m2.  Females not of childbearing potential - defined as post-menopausal for at least 1 year, or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) - or practicing at least one of the following medically acceptable methods of birth control throughout the study period:  Hormonal methods such as oral, implantable, injectable, or transdermal contraceptives for a minimum of 1 full cycle (based on the subject's usual menstrual cycle period) before study drug administration; Total abstinence from sexual intercourse since the last menses before study drug administration; Intrauterine device; Double barrier method (condoms, sponge, diaphragm, with spermicidal jellies or cream). Male subjects capable of fathering a child must be willing to use barrier methods to avoid a pregnancy during the study. Male condoms with or without a spermicide coating are acceptable, as some women are allergic to spermicide. Willing and able to understand the study requirements, abide by the study restrictions, complete the study procedures, independently record responses on the pain scales and make daily/weekly entries using the NEForm (section K1), and independently communicate meaningfully with study personnel. Willing to refrain from illicit drug use during the study, and to have illicit drug testing at screening and at later time points, if illicit drug use is suspected during the study. Illicit drug use is defined as the use of any medication or substance that is outside the prescribed use of a medical professional, including medications that are prescribed but are not being used as prescribed. Cannabinoid use is exclusionary for this trial, regardless of reason for use. Subjects must stop taking any current analgesic medications at the time of initial Screening and agree to take only the allowed rescue medication for OA knee pain (acetaminophen; 325mg x 2 tablets PO, QID, PRN) from the time of screening through study completion, and agree to use no topical medications for OA knee pain during the trial. Subjects must also stop taking any medication known to impact pain, even if taken for other indications, e.g. duloxetine for depression. Complete the SAFER (State, Assessibility, Face and Ecological Validity and the Rule of the 3 Ps [persistent, pervasive, pathological]) interview and receive a passing score which will be administered by a remote telephone rater to confirm pain history with knee OA, eligibility per study pain intensity requirements, screening EMA score, and medication history.  Exclusion Criteria:  Any form of joint replacement surgery of the index knee at any time, or open surgery of the index knee/knee joint in the past. Prior arthroscopic surgery of the index knee within 3 months of Screening. Any painful conditions of the index knee due to disease other than OA. For example, periarticular or referred pain involving the index knee, or from joint disease other than OA associated with the index knee. Other chronic pain anywhere in the body that is equal or greater in intensity or impairment than index knee pain or that requires the use of analgesic medications including, but not limited to, local painful areas, myofascial pain syndromes, fibromyalgia, genetic, metabolic abnormalities, hematologic or neuropathic pain, and any acute or chronic pain that may interfere with the study pain assessments by the subject. Secondary OA of the index knee due to acute or recurrent traumatic injury. Significant current or past instability (e.g., cruciate ligament tear or rupture or previous repair) or misalignment (>10 degrees varus or valgus) of the index knee. Documented history of neuropathic arthropathy in the knee. Imaging finding of bony fragmentation in the index knee (radiographic, computed tomography, or magnetic resonance imaging). Physical/occupational/chiropractic therapy for the lower extremities or acupuncture for the lower extremities within 30 days of Screening, or need for such therapy during the study. Plans to have surgery, or other invasive procedures, or intra-articular (IA) injections while participating in the study. Current use of opioids for any condition. Use of pain medication (including non-steroidal anti-inflammatory drugs, medical cannabinoids/ CBD oil) less than 5 days before screening (acetaminophen is allowed) or any time throughout the study. Corticosteroid injection in the index knee within 90 days of Screening or during study participation. Received IA viscosupplementation (e.g., Synvisc®, Hyalgan®) within 90 days of Screening or any time during study participation. History of clearly documented allergic reaction to celecoxib (Celebrex®), or to sulfa drugs. Knee effusion requiring aspiration of the index or contralateral knee at time of screening. Radiofrequency ablation (RFA) of the knee within 2 years prior to screening. Presence of any medical condition or unstable health status that, in the judgment of the investigator, might adversely affect the safety of the subject or the conduct of the study, or negatively affect the resulting data, including chronic conditions that are likely to alter the rate of healing or are likely to result in safety complications unrelated to the study medication, or significant compromise to key organ systems. Has a malignancy or has received treatment for malignancy at any time, with exception of resected basal cell carcinoma and squamous cell carcinoma of the skin within the past 5 years. Ulcer or open wound anywhere in the region of the index knee. Clinically significant abnormal laboratory results at the Screening Visit (in the opinion of the investigator), or significant organ disease that would put the subject at undue risk or affect the ability of the subject to participate in the trial. Use of an investigational medication within 30 days of Screening, or 5 pharmacokinetic or pharmacodynamic half-lives (whichever is longer) or scheduled to receive such an agent while participating in the current study.  Has any of the following characteristics:  active or historic substance use disorder within the previous year as defined by the Diagnostic and Statistical Manual for Mental Health Disorders, fifth edition, or urine drug screen is positive for a substance of abuse and participant is unable to provide a valid prescription from a medical professional. Has moderate to severe depression or anxiety, as indicated by a score ≥ 11 on either subscale of the Hospital Anxiety or Depression Scale (HADS). Has a positive pregnancy test at the Screening Visit. Has ongoing litigation for workers compensation. Known history or symptoms of long QT syndrome. Male has a QRS interval >120 ms and QTcF ≥460 ms OR female has a QRS interval ≥120 ms and QTcF ≥480 ms at Screening or Baseline. Has moderate to severe congestive heart failure (New York Heart Association [NYHA] class III and class IV). Has a history of symptomatic cardiovascular disease. K-L Grade 1 or 4 OA in the index knee. Current therapy with any immunosuppressive therapy, including corticosteroids (>5 mg/day of prednisone).