Study of Safety, Tolerability, Preliminary Efficacy of Intra-articular LNA043 Injections in Patients With Articular Cartilage Lesions and Knee Osteoarthritis.
Condition: Osteoarthritis
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Intervention: LNA043; Placebo
Intervention description: LNA043 intra-articular injection; Placebo intra-articular injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A total of 142 participants were randomized, but only 141 received treatment. One participant in Part B was discontinued due to poor veins that were not adequate for blood samples.
Masking: Double (Participant, Investigator)
Enrollment: 142.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Articular cartilage; partial thickness cartilage lesion; knee cartilage; regeneration; osteoarthritis; adult

Summary:

      The purpose of this two-part study is to assess the efficacy, safety and tolerability of
      multiple intra-articular (i.a.) injections of LNA043, in regenerating the articular surface
      in patients with cartilage lesions of the knee (Part A) and knee osteoarthritis (Part B).
    

Eligibility criteria:

        Inclusion criteria Part A

          -  Patient was ≥18 and ≤55 years old at time of screening.

          -  Patient had a body mass index (BMI) <30 kg/m2 at screening,

          -  Patient had 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 had an onset of pain and impairment of function between two (2) months and two
             (2) years before screening.

          -  Patient had a grade 2 or 3 OA of the knee with Joint Space Width (JSW) 2-4 mm
             evaluated with X-Ray at screening

        Inclusion criteria Part B

          -  Patient was ≥18 and ≤75 years old at time of screening.

          -  Patient had 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 must have had 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.

          -  Patient had a K&L grade 2 or 3 OA of the knee with JSW 2.00-4.00 mm (X=0.225) fixed
             position evaluated with X-Ray by the Central Reader at 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 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 had 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 had 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 had patellofemoral dysplasia Dejour Grade B-D based on X-ray evaluation
             performed within 9 months from screening

          -  Patient had 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 had 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.