Study on Safety, Tolerability and Prelimenary Efficacy of LNA043 in Patients Undergoing Autologous Chondrocyte Implantation
Condition: Knee Cartilage Lesion
Intervention: LNA043; placebo to LNA043
Intervention description: LNA043 Single dose; placebo to LNA043 single dose
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: cartilage lesion, ACI

Summary:

      The purpose of this study was to assess safety, tolerability, pharmacokinetics and
      preliminary efficacy of a single intra-articular (i.a.) administration of LNA043 in
      regenerating the articular cartilage of the knee, in a standardized clinical scenario of
      acute cartilage defect. The study aimed at characterizing the mechanism of action of LNA043
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent must be obtained before any assessment is performed

          -  Patient is ≥18 and≤ 50 years old at time of screening

          -  Patient has a body mass index (BMI) <30 kg/m2 at screening

          -  Patient has a localized articular cartilage defect of the knee and is scheduled for an
             ACI procedure

          -  Able to communicate well with the investigator, to understand and comply with the
             requirements of the study.

        Exclusion Criteria:

          -  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 6 months from screening

          -  Patient has unstable knee joint or insufficiently reconstructed ligaments, based on
             medical history and physical examination by the investigator.

          -  Patient scheduled for a concomitant articular surgical procedure (e.g., anterior
             cruciate ligament reconstruction) other than debridement or partial meniscectomy

          -  Patient has malalignment (valgus- or varus-deformity) in the target knee ≥ 5° based on
             based on X-ray evaluation performed within 6 months from screening.at screeningmedical
             history. In suspected cases, the mechanical axis must be established radiographically
             through complete leg imaging during standing and in postero-anterior projection.

          -  Patient has a known autoimmune disease, inflammatory arthropathy (including but not
             limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, CPPD,
             gout), active acute or chronic infection of the joint, recent Lyme disease to the
             knee, systemic cartilage disorder, or a known systemic connective tissue disease.

          -  Patient has had surgical treatment of the target knee using autologous osteochondral
             transplantation/mosaicplasty within 12 months prior to screening (Note: prior
             diagnostic arthroscopy with debridement and lavage, meniscal surgery, microfracture,
             anterior cruciate ligament reconstruction, and extra-articular surgery e.g.,
             high-tibial osteotomy are acceptable).

          -  Patient is unable to undergo magnetic resonance imaging (MRI) or presents absolute
             contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker,
             defibrillator).

          -  Patient taking medications prohibited by the protocol: corticosteroids by any route
             (except topical) from 4 weeks prior to screening; nonsteroidal anti-inflammatories or
             aspirin (greater than 100 mg per day) within 2 weeks prior to screening; paracetamol
             greater than 3000 mg per day within 2 weeks prior to screening; glucosamine or
             chondroitin sulfate within 2 weeks prior to screening; any local treatment i.a. into
             the knee within 3 months from screening.

          -  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 (use of tobacco/nicotine products in the previous 3 months > 5
             cigarettes/day). Urine cotinine levels will be measured during screening for all
             subjects. Regular smokers will be defined as any subject who reports tobacco use of >
             5 cigarettes/day and/or who has a urine cotinine ≥ 500 ng/mL.