Acute cartilage injuries MedDRA version: 20.0 Level: PT Classification code 10031161 Term: Osteoarthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Code: LNA043
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: TBD
Current Sponsor code: LNA043
Concen
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Written informed consent must be obtained before any assessment is performed • Patient is =18 and= 45 50 years old at time of screening • Patient has a body mass index (BMI) =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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. 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 childbearing 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: as above; Main Objective: • To assess the efficacy of a single LNA043 i.a. injection in regenerating hyaline cartilage tissue at the donor sites of patients undergoing autologous chondrocyte implantation (ACI) • To assess safety and tolerability of a single LNA043 i.a. injection in patients undergoing ACI ; Secondary Objective: • To assess extent and quality of the repair tissue at the donor site before surgery • To assess over a longer term the extent and quality of filling of the donor site • To evaluate local and systemic pharmacokinetics (PK) of LNA043 following a single i.a. administration • To assess the potential immunogenicity of LNA043 ; Primary end point(s): • Cartilage glycosaminoglycan (GAG) content and bi-layer collagen organization based on 7Tesla MRI at Week 4 • Safety at week 28 (Adverse Events, ECGs, Vital signs, Hematology, blood chemistry, urinalysis, Physical examination) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: as above; Secondary end point(s): • International Cartilage Repair Society (ICRS) II histology scoring system at Week 4 • Percentage (%) of donor sites filling based on 7Tesla MRI at Week 4 • Percentage (%) of donor site filling based on 7Tesla MRI at Week 12 and 28 • Cartilage GAG content and bi-layer collagen organization estimated using 7Tesla MRI at Week 12 and 28 • Serum PK profile of LNA043 i.e., Cmax and AUC • Concentration of LNA043 in synovial fluid at Week 4 • Presence and characterisation of anti-LNA043 antibodies in serum at Day 1 (predose), Day 8, 29, 85, 197 | — |
Countries
Austria
Contacts
Public ContactDrug Regulatory Affairs
Novartis Pharma GmbH
Outcome results
None listed