Osteoarthritis
Conditions
Interventions
Three treatment arms are planned to test repeated dosing with three consecutive
i.a. injections of either LRX712 15 mg, LRX712 25 mg or placebo.
Sponsors
Novartis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Patient must be between 35 and 75 years old at screening - Patient must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 35 kg/m2 at screening. BMI = Body weight (kg) / [Height (m)]2 at screening - Patient must have knee osteoarthritis (OA) at screening. Structural signs of Radiographic OA need to be confirmed by radiography taken in standing weight-bearing fixed flexion position and PA view, indicating Kellgren-Lawrence grade 2 or 3 in the index knee - Patient must have symptomatic disease predominantly in one (the index) knee, with minimal or no symptoms in the contralateral knee. Symptomatic disease is defined as having pain in the knee >= 4 days of the week for at least 3 months at screening. - Patient must have radiographic confirmation of a medial joint space width of 1.5 to 3.5 mm for females, or 2 to 4 mm for males, measured at the X=0.225 fixed point location within the medial tibio-femoral compartment of the index knee, at screening. - Patients must be ambulatory at screening (walk without aid)
Exclusion criteria
Exclusion criteria: - Patient has a known autoimmune disease, inflammatory or chronic arthropathy other than OA (including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, SLE, (systemic lupus erythematosus), CPPD (calcium pyrophosphate dihydrate crystal deposition disease),, gout and fibromyalgia), active acute or chronic infection of the joint, Lyme disease involving the knee, systemic cartilage disorder, or a known systemic connective tissue disease - Subject has had surgical treatment of the target knee using mosaicplasty, microfracture, or resecting more than 50% of meniscal tissue - Subject has symptomatic, isolated patello-femoral pain in the index knee as per the Investigator's examination - Subject has malalignment (valgus- or varus-deformity) in the index knee >= 7.5° as per anatomic PA axis measured by weight-bearing short knee radiography. - Effusion in the index knee that clinically requireding aspiration in the past 12 weeks prior to screening, or that is clinically relevant in the index knee as per physical examination (bulge sign, patellar tap) at screening or Day 1 - Any local i.a. treatment to the knee, including but not restricted to viscosupplementation and corticosteroids, within 12 weeks prior to screening - Signs or symptoms, in the judgment of the investigator, of a clinically significant systemic viral, bacterial or fungal infection within 30 days prior to screening; COVID-19 specific: It is highly recommended that PCR or antigen testing for COVID-19 be completed within 1 week prior to first dosing. If testing is performed, negative test results are required prior to enrollment into the study. Additional testing may occur at the discretion of the investigating physician. This requirement may be ignored if the pandemic is declared ended by the country where the site is located, and resumed if the pandemic recurs.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in the medial femoral condyle cartilage volume in the index region measured by 7T MRI from baseline to week 28 in LRX712- vs. placebo-treated patients | — |
Secondary
| Measure | Time frame |
|---|---|
| - PK parameters in plasma : Tmax, Cmax, Cmin in plasma - PK parameter in synovial fluid : Concentration at Day 1, Week 4, Week 8 post dosing - Vital signs (blood pressure, heart rate, temperature) as per assessment schedule - Hematology, blood chemistry and urinalysis as per assessment schedule - Local and Systemic Adverse Events - ECG parameters (PR, QRS, heart rate, RR, QT, QTc) as per assessment schedule - Change in articular cartilage [23Na] content from baseline compared to placebo measured with 7T MRI at Week 16, 28 and 52 in LRX712- vs. placebo-treated patients - Change in the medial femoral condyle cartilage (volume) measured by 7T MRI from baseline to Weeks16 and 52. | — |
Countries
Netherlands
Outcome results
None listed