Atri ONE Mechanism of Action

Pharmacology: Pharmacodynamics: When this product is injected into the joint cavity of a surgically induced rabbit osteoarthritis model, it increases the articular thickness of the knee joint and inhibits inflammatory edema around the joint, reduces the area of cartilage damage, inhibits the increase in the elongation angle of the knee joint, and inhibits the increase in the Makin score of the femur and tibia articular cartilage. In addition, it also inhibits the increase in joint thickness through reduction and inhibition of the thickness of articular cartilage and the number of chondrocytes, and has an anti-inflammatory effect by inhibiting IL-1β and TNF-α activity, which are inflammatory cytokines.
Pharmacokinetics: Absorption: The maximum plasma concentration (Cmax) of this product after intra-articular injection in non-fasting rats was reached at an hour after injection, and the median of the maximum plasma concentration reached at 9.88 hours. The maximum plasma concentration (Cmax) after subcutaneous injection in non-fasting rats was reached at an hour after injection, and the median of the maximum plasma concentration reached at 452 hours.
Distribution: After 2,400 hours of intra-articular injection, it was confirmed that 73.98% of the dose remained in most joint cavities. It was distributed in all tissues, and the concentration in all tissues, except for the injection site, decreased over time. It was also distributed in all tissues after subcutaneous injection and the concentration in all tissues decreased over time, but it was confirmed that it was removed more slowly than intra-articular injection.
Metabolism: After subcutaneous injection of this product, it was confirmed that various metabolites with a molecular weight of 21,100 Da or less were present in plasma, and it was also confirmed that metabolites with a molecular weight of 6,100 Da or less were mainly excreted in urine, which is the main excretion route.
Excretion: After intra-articular injection, 26.9% and 5.1% of this product was observed in urine and feces, respectively, and 68.8% of the injected dose was observed at the injection site. After subcutaneous injection, 19.9% and 3.7% were observed in urine and feces, and 74.6% of the injected dose was observed in all tissues.
Toxicology: Preclinical Safety data: Clinical Trial Information: Double-blind, Placebo-controlled Clinical Trial (YY_YYD302_001/2a): A multicenter, randomized, placebo-controlled, double-blind trial was conducted to compare and evaluate the safety and efficacy of the three groups in patients with osteoarthritis of the knee joint after receiving a single dose of this product and placebo. As a result of comparing the changes in pain score (WBP-100 mm VAS: pain assessment during weight bearing) at 12 weeks after injection of this product (2 mL: 12 subjects, 3 mL: 12 subjects) and placebo (3 mL: 6 subjects), the group receiving this product (2 mL), the group receiving this product (3 mL), and the group receiving the placebo (3 mL) showed a statistically significant decrease of -34.20±24.10 mm, -23.10±21.79 mm, and -29.00±33.15 mm, respectively.
Double-blind, Active-controlled Clinical Trial (YY_YYD302_003): A multicenter, randomized, active-controlled, double-blind trial was conducted to compare and evaluate the safety and efficacy in patients with osteoarthritis of the knee joint between the two groups after receiving a single injection of this product and the active comparator (Synovian). As a result of comparing (PP group) the pain score (WBP-100 mm VAS: pain assessment during weight bearing) at 12 weeks after injection of this product (95 subjects) and the active comparator (88 subjects), the WBP-100 mm VAS was decreased by an average of 31.76±18.93 mm for this product and an average of 29.74±20.54 mm for the active comparator compared to the baseline, statistically demonstrating non-inferiority between the two groups.
Re-injection Clinical Trial (YY_YYD302_003): A multicenter, randomized, active-controlled, double-blind trial was included in the clinical trial and conducted to confirm the safety and efficacy of this product for up to 6 months after a single injection in patients with osteoarthritis of the knee and to further evaluate the safety and efficacy of re-injection. WBP-100 mm VAS decreased by an average of 39.06±13.15 mm compared to the baseline at 12 weeks after a single dose (80 subjects, PP group), and decreased by 37.72±16.83 mm at 24 weeks.WBP-100 mm VAS at 36 weeks for subjects who were re-injected at 24 weeks (47 subjects) decreased by an average of 5.45±13.14 mm compared to the baseline (24 weeks). Safety and efficacy for long-term use other than the period revealed through clinical studies have not been confirmed.
Toxicity Test: Single Toxicity: When a single dose was injected intraperitoneally and intra-articularly to rats and beagle dogs up to the maximum feasible dose (MFD), the lethal dose exceeded the MFD in both genders, and no deaths were found.
Repeat Toxicity: This product was injected intra-articularly to rats at doses of 30, 60, and 120 μL/head/day, 8 times repeatedly at 4-week intervals, and to beagle dogs at doses of 2, 4, and 6 mL/head/day, 8 times repeatedly at 16-week and 40-week intervals. No toxicologically significant changes were observed at any dose.
Genotoxicity: Mutagenicity and chromosomal aberration were not found in the genotoxicity test of the reverse mutation test using bacteria, the chromosomal aberration test using CHL cells, and the micronucleus test using ICR mouse.
Antigenicity: It did not show antigenicity in the active systemic anaphylactic shock (ASA) response test and allogeneic passive cutaneous anaphylaxis (PCA) response test using Hartley guinea pigs.