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

Inclusion criteria

- 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.

Exclusion criteria

- 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.

- 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 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.

- Patients with patellofeoral dysplasia Dejour and patients with malalignment, X-ray
requirement not limited to 9 months.

- 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.

Prohibited medication updated with reference to dosing (formerly screening).