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
This was a non-confirmatory, patient and investigator blinded, randomized, placebo-controlled, parallel group, single dose study in patients with cartilage lesions undergoing autologous cartilage implantation (ACI). Participants were treated only on one occasion (Day 1) with a single i.a. injection that was performed under arthroscopic visualization and followed up for 28 weeks. Originally approximately 22 patients were planned to be enrolled in two cohorts (LNA043 20 mg and LNA043 40 mg). The study was terminated before any patient was randomized into the LNA043 40 mg cohort
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
14
LNA043 Single dose
placebo to LNA043 single dose
Novartis Investigative Site
Vienna, Austria
Novartis Investigative Site
Vienna, Austria
Change From Baseline in GAG Content
Sodium MRI-based measurements of change from baseline in glycosaminoglycan (GAG) content were assessed from both defective sites and a nearby healthy cartilage region (as a reference tissue). Specifically, the ratio of normalized sodium signal in the surgically created defect (SCD or donor site) to healthy non-weight bearing region (HNWB), i.e. SCD/HNWB and the defect to be treated (DTBT or main lesion) to healthy weight bearing region (HWB), i.e. DTBT/HWB was of major interest
Time frame: Baseline, Week 4
Bi-layer Collagen Organization Based on MRI Measurements
MRI T2 maps were generated and zonal T2 ratios (superficial layer T2 / deep layer T2) were calculated to assess the collagen fiber organization in the surgically created defect (SCD) and defect to be treated (DTBT) cartilage regions.
Time frame: Week 4
Change From Baseline in International Cartilage Repair Society (ICRS) Scoring
Extent of the repair tissue at the donor site before surgery. Each criterion was evaluated based on the visual analog scale and graded from 0 (best) to 100 (worst).
Time frame: Week 4
Percentage of Donor Site Refilling Based on MRI Measurements.
Extent of filling of the donor site over a longer term. Percentage change from baseline in refilling of cartilage defect based on 7T MRI for donor Region.
Time frame: Baseline, Week 4, Week 12 and Week 28
Change From Baseline in GAG Content
Sodium MRI-based measurements of change from baseline in glycosaminoglycan (GAG) content was assessed from both defective sites and a nearby healthy cartilage region (as a reference tissue). Specifically, the ratio of normalized sodium signal in the surgically created defect (SCD or donor site) to healthy non-weight bearing region (HNWB), i.e. SCD/HNWB was of major interest
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Time frame: Baseline, Week 12 and Week 28
Bi-layer Collagen Organization Based on MRI Measurements
MRI T2 maps were generated and zonal T2 ratios (superficial layer T2 / deep layer T2) were calculated to assess the collagen fiber organization in the SCD cartilage region.
Time frame: Week 12 and Week 28
PK Profile of LNA043 and of AngPTL3 in Serum Cmax
Local and systemic pharmacokinetics (PK) of LNA043 following a single i.a. administration
Time frame: 4 weeks
PK Profile of LNA043 and of AngPTL3 in Serum AUC
Local and systemic pharmacokinetics (PK) of LNA043 following a single i.a. administration
Time frame: 4 weeks
Number of Participants With Anti-LNA043 Antibodies in Serum
Potential immunogenicity of LNA043
Time frame: Baseline, Week 1, Week 4, Week 12 and Week 28