One hundred and fourty patients with mild-to-moderate knee osteoarthritis were randomized per-protocol to receive WDTE60N 250 mg once daily (n = 70) or matching placebo (n = 70). The primary outcome was change in 100-mm VAS pain from baseline to Day 90. Secondary outcomes included VAS at interim time points; KOOS subscales (Pain, Symptoms, ADL, Sport/Rec, QoL); serum hsCRP, TNF-α, IL-6, IL-1β at Days 45 and 90; Subject’s and Physician’s Global Assessment (SGA/PGA) at Day 90; and safety. Outcomes were assessed from Day 3 to Day 90. Overall, the results of the study revealed greater VAS pain reduction with WDTE60N versus placebo by Day 90 (mean change 14.41 vs 6.02; p < 0.0001) with separation evident as early as Day 7; KOOS subscales and inflammatory biomarkers also favored WDTE60N; SGA/PGA scores were lower (better) with WDTE60N; and adverse events were few and mild. These findings suggest that a once-daily low dose of WDTE60N can meaningfully reduce pain and improve function and inflammation markers over 3 months in knee OA.