Study of Safety, Tolerability, Preliminary Efficacy of Intra-articular LNA043 Injections in Patients With Articular Cartilage Lesions and Knee Osteoarthritis.

This is an interventional treatment trial for Wounds and Injuries focused on measuring Articular cartilage, partial thickness cartilage lesion, knee cartilage, regeneration, osteoarthritis, plaque-type psoriasis, metabolic syndrome, Secukinumab, lifestyle intervention, systemic inflammation, metabolism Read More

Inclusion criteria Part A

• Patient is ≥18 and ≤55 years old at time of screening.
• Patient has a body mass index (BMI) <30 kg/m2 at screening, for patients with BMI >30 but ≤ 33kg/m2, eligibility will be decided by consultation with the sponsor.
• Patient has a symptomatic, single, articular cartilage defect of one knee, grade II or IIIA according to the ICRS classification, localized to either the femoral condyles/femoral trochlea or to the patella, based on MRI or arthroscopy performed within 9 months before screening visit and confirmed by screening 3T MRI.
• Patient has an onset of pain and impairment of function between two (2) months and two (2) years before screening.
• Patient reports a KOOS (sports and recreational activities subscale) score of ≤ 60 at both screening and Day 1.

Inclusion criteria Part B

• Patient is ≥18 and ≤75 years old at time of screening.
• Patient has a body mass index (BMI) ≤ 35 kg/m2 at screening
• Diagnosis of femorotibial osteoarthritis (OA) in the target knee by standard American College of Rheumatology (ACR) criteria at study start (clinical AND radiographic criteria)
• Patient has a Kellgren & Lawrence (K&L) grade 2 or 3 OA of the knee with Joint Space Width (JSW) 2-4 mm evaluated with X-Ray at screening.
• 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 more than 50% of the days during the last 3 months from screening.

Exclusion criteria Part A & B

• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 15 days after stopping of investigational drug.
• Patient has had surgical treatment of the target knee using mosaicplasty, microfracture, meniscectomy >50% (Note: prior diagnostic arthroscopy with debridement and lavage, <50% meniscectomy, lateral release, patellar realignment, medial patellofemoral ligament reconstruction are acceptable if performed at least 2 months prior to screening; anteriorcruciate ligament reconstrucion is acceptable if performed 12 months prior to screening, or less if restoration of joint function is evident, and agreed by the sponsor).
• Patient has an unstable target knee joint or insufficiently reconstructed ligaments based on medical history and physical examination by the investigator.
• Prohibited medication updated with reference to dosing (formerly screening).

Exclusion Criteria Part A only

• Regular smokers (> 5 cigarettes/day). Urine cotinine levels will be measured during screening for all patients. Regular smokers will be defined as any patient who reports tobacco use of > 5 cigarettes/day and/or who has a urine cotinine ≥ 500 ng/mL.
• Patient has radiologically apparent degenerative joint disease in the target knee as determined by Kellgren and Lawrence grade ≥2 based on X-ray evaluation performed within 9 months from screening.
• Patient has patellofemoral dysplasia Dejour Grade B-D based on X-ray evaluation performed within 9 months from screening
• Patient has malalignment (valgus- or varus-deformity) in the target knee ≥ 5° based on X-ray evaluation performed within 9 months from screening. In suspected cases, the mechanical axis must be established radiographically through complete leg imaging during standing and in postero-anterior (PA) projection.

Exclusion Criteria Part B only

• Regular smokers (> 10 cigarettes/day).
• Clinical signs of inflammation (i.e., redness) in the target knee.
• History of knee replacement (unilateral or total) in either knee.
• Presence of severe hip OA conditioning lower limb function according to PI's evaluation.
• Nephrotic syndrome and/or significant proteinuria
• History of coagulopathy or medical condition requiring anticoagulation which would preclude knee injection
• Patient has malalignment (valgus- or varus-deformity) in the target knee ≥ 7.5° based on X-ray evaluation. In suspected cases, the mechanical axis must be established radiographically through complete leg imaging during standing and in postero-anterior (PA) projection.