Evaluation of Intra-articular CX-011 to Treat Moderate to Severe Pain From Knee Osteoarthritis

The primary objective of the study is to assess the safety and tolerability of three escalating doses of CX-011 (100, 300, and 1000 μg) following a single intra-articular administration. Safety assessments will include the incidence and severity of local and systemic adverse events, procedure- and product-related serious adverse events, physical examinations, index knee evaluations, vital signs, electrocardiograms, and safety laboratory tests. Dose-limiting toxicities and the maximum tolerated dose will be determined based on these assessments.

Secondary objectives focus on evaluating the preliminary efficacy of CX-011 for the treatment of knee osteoarthritis pain and function, as well as further characterization of its safety profile. Efficacy endpoints include changes from baseline in pain intensity measured by the Visual Analog Scale (VAS) at 4, 12, and 24 weeks post-injection, as well as percentage improvements in the pain and function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at the same time points.

Up to 72 patients will participate in this study (in one study center). The expected length of participation in the study is about 28 weeks including the screening period.

Inclusion criteria

• Written consent to participate in the study.
• Males or females 18 years of age or less than 75 years old.
• Diagnosis OA of the index knee by a combination of clinical and radiographic findings wherein the index knee is self-identified by the patient as the more severe knee and symptoms have persisted for 3 months.
• Radiographic evidence of OA in the tibiofemoral compartment of the index knee (Kellgren-Lawrence grades II or III) within 6 months prior to Screening or during the Screening period.
• Index knee pain on most days (greater than 15) over the last month
• Patients who have failed to adequately respond for at least 6 months within the previous 12 months to at least two osteoarthritis therapies that include least 1 pharmacological treatment such as simple analgesics (e.g., acetaminophen); nonsteroidal anti- inflammatory drugs (NSAIDS) conservative, non-pharmacological therapy; avoidance of activities that cause joint pain; exercise; weight loss; physical therapy; and removal of excess fluid from the knee.
• VAS Pain score of 40-80 on a 0 - 100 scale to be reconfirmed at time of treatment.
• Overall index knee pain score of 11 or more in the index knee using the 0 - 20 WOMAC Pain scale.
• hsCRP greater or equal 2 mg/L
• Body mass index less than 40 kg/m2
• If female, must not be pregnant or nursing and willing to refrain from becoming pregnant.
• Willing to agree not to use illicit drugs 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.
• Able to comply with study requirements and complete the full sequence of protocol-related procedures and evaluations, including post-hospitalization, outpatient, and follow-up visits and ability to follow verbal and written instructions.

Exclusion criteria

• Daily use of assistive devices (e.g. cane or walker) or presence of comorbidities that would limit the patient's ability to walk.
• History of Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, sarcoidosis or amyloidosis.
• Unstable joint (such as a torn anterior cruciate ligament)
• Inability to undergo Magnetic Resonance Imaging (MRI) due to presence of surgical hardware or other foreign body in the index knee, or because of patient's claustrophobia
• Regular use of anticoagulants
• Symptoms of locking, intermittent block to range of motion, or loose body sensation that could indicate meniscal displacement or an IA loose body; knee ligament instability.
• Major dysplasias or congenital abnormalities
• Corticosteroid injection into the index knee within 3 months prior to screening; extended-release steroid use within 4 months prior to screening.
• Viscosupplement (e.g., hyaluronic acid [HA]) injection, platelet-rich plasma injection, bone marrow aspirate or bone marrow aspiration concentrate, placental-derived tissue/cells, adipose tissue, or any other autologous or allogeneic product) into the index knee within 3 months prior to screening.
• Knee surgery or procedure on the index knee within 12 months prior to screening and/or planned knee surgery during the study including cold or radiofrequency nerve ablation.
• Knee surgery or procedure on the contralateral knee within 6 months prior to screening and/or planned knee surgery during the study including cold or radiofrequency nerve ablation.
• Acute index knee trauma within 3 months prior to screening.
• Knee joint infections, skin diseases or infections in the area of the injection site.
• Current therapy with any immunosuppressive therapy, including corticosteroids (> 5 mg/day of prednisone) or patients with conditions that would likely include treatment with immunosuppressive therapy (including corticosteroids) during the study period.
• HbA1c > 8% and/or insulin-dependent diabetes
• Average systolic BP > 160 mmHg or diastolic BP > 100 mmHg on > 3 blood pressure medications.
• Clinically significant findings on physical examination or screening tests (e.g. laboratory and radiographic) that are not specific to OA of the knee and may interfere with study conduct or interpretation of data or increase patient risk.
• Clinically significant intercurrent illness, medical condition, non-knee pain, or medical history (including neurological or mental illness, human immunodeficiency virus, autoimmune diseases or connective tissue disorder, fibromyalgia, complex regional pain syndrome, clinical anxiety, clinical depression, any active infection including hepatitis B or C) that would jeopardize patient safety, limit participation, or compromise interpretation of data derived from the patient.
• Participation in another clinical trial within the previous 30 days before screening or planned participation in another clinical trial within the study period