A randomized, placebo-controlled, patient and investigator blinded study investigating the safety, tolerability and preliminary efficacy of 8-week treatment with intra-articular LRX712 to regenerate articular cartilage in patients with mild/moderate knee osteoarthritis
- Conditions
- Osteoarthritis10023213
- Registration Number
- NL-OMON52598
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 30
- 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)
- 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Change in the medial femoral condyle cartilage volume in the index region<br /><br>measured by 7T MRI from baseline to week 28 in LRX712- vs. placebo-treated<br /><br>patients</p><br>
- Secondary Outcome Measures
Name Time Method <p>- PK parameters in plasma : Tmax, Cmax, Cmin in plasma<br /><br>- PK parameter in synovial fluid : Concentration at Day 1, Week 4, Week 8 post<br /><br>dosing<br /><br>- Vital signs (blood pressure, heart rate, temperature) as per assessment<br /><br>schedule<br /><br>- Hematology, blood chemistry and urinalysis as per assessment schedule<br /><br>- Local and Systemic Adverse Events<br /><br>- ECG parameters (PR, QRS, heart rate, RR, QT, QTc) as per assessment schedule<br /><br>- Change in articular cartilage [23Na] content from baseline compared to<br /><br>placebo measured with 7T MRI at Week 16, 28 and 52 in LRX712- vs.<br /><br>placebo-treated patients<br /><br>- Change in the medial femoral condyle cartilage (volume) measured by 7T MRI<br /><br>from baseline to Weeks16 and 52.</p><br>