Safety, Tolerability and Preliminary Efficacy of Multiple Intra-articular Injections of LRX712 in Patients With Knee OA

Recruitment & Eligibility

Inclusion Criteria

Written informed consent must be obtained before any assessment is performed.

To be eligible for inclusion in this study patients must meet all of the following criteria:

Patient must have a BMI between 18 -35 kg/m2
Patient must have symptomatic knee osteoarthritis predominantly in one knee (index knee)
Patient must have knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) in the index knee, as confirmed by radiography
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 within the medial tibio-femoral compartment of the index knee

Exclusion Criteria

Subjects meeting any of the following criteria are not eligible for inclusion in this study:

Patient has a known autoimmune disease, inflammatory or chronic arthropathy
Patient had partial or complete joint replacement in one or both knees
Patient has symptomatic, isolated patello-femoral pain in the index knee as per the Investigator's examination
Pregnant or nursing (lactating) women
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.
Previous use of LRX712 or use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations
Patient has malalignment (valgus- or varus-deformity) ≥ 7.5° in the index knee as per anatomic PA axis measured by weight-bearing short knee radiography
History of significant cardiac conduction/electrophysiological disorder, e.g. familial long QT syndrome or known family history of Torsades de Pointes or prolonged QT syndrome or QTcF ≥ 450 msec (Fridericia Correction) for males and ≥ 460 msec for females at screening or baseline (by local 12-lead digitized ECG reading)
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.

Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

Arm && Interventions

Group	Intervention	Description
LRX712 Arm 1	LRX712	Randomized in a 1:1:1 ratio: LRX712 Arm 1:LRX712 Arm 2:placebo
LRX712 Arm 2	LRX712	Randomized in a 1:1:1 ratio: LRX712 Arm 1:LRX712 Arm 2:placebo
Placebo	Placebo	Randomized in a 1:1:1 ratio: LRX712 Arm 1:LRX712 Arm 2:placebo

Primary Outcome Measures

Name	Time	Method
Changes from baseline in cartilage volume in the medial femoral condyle at Week 28	Baseline and Week 28	Efficacy of multiple intra-articular injections of LRX712 in regenerating cartilage as measured with 7T MRI

Secondary Outcome Measures

Name	Time	Method
Changes in articular cartilage [23Na] content from baseline compared to placebo at Week 16, 28 and 52	Baseline, Week 16, 28 and 52	Efficacy of multiple intra-articular injections of LRX712 measured with 7T MRI
Changes from baseline in cartilage volume in the medial femoral condyle at Week 16 and 52	Baseline, Week 16 and 52	Efficacy of multiple intra-articular injections of LRX712 measured with 7T MRI
Time to Reach the Maximum Plasma Concentration (Tmax)	Pre-dose to 28 weeks	The observed time to reach max (Tmax) plasma concentration following drug administration
Maximum Observed Plasma Concentration (Cmax)	Pre-dose to 28 weeks	The observed maximum (Cmax) plasma concentration following drug administration
Concentration in synovial fluid	Day 1; week 4; week 8	The observed synovial concentration following drug administration
Local and systemic adverse events	Day 1 to 52 weeks	Safety and tolerability of multiple intra-articular injections of LRX712
Minimum Observed Plasma Concentration (Cmin)	Pre-dose to 28 weeks	The observed minimum (Cmin) plasma concentration following drug administration

Recruitment & Eligibility