Introduction. Previous phase 1 and 2b studies in patients with degenerative disc disease (DDD) show that STA363 dose-dependently reduces disc height and dehydrates the nucleus pulposus (NP), suggesting a chemonucleolytic effect of STA363 in the treatment of symptomatic lumbar disc herniation (LDH). The present study was conducted to establish safety and tolerability in LDH patients, and to assess the effects on disc volume, height and water content (intensity of NP via T2-weighted MRI).
Methods. In a placebo-controlled, randomized, double-blind, parallel design phase 1b study on 25 patients with LDH, STA363 (S-lactic acid (120 mg/mL) in Omnipaque, 1.5 mL, 17 patients) or placebo (1.5 mL of Omnipaque, 8 patients) was injected into the symptom-generating herniated lumbar disc (Pfirrmann grade ≤3). The patients were followed for up to 6 months with double echo MRI at baseline, 1, 3 and 6 months. The primary objective was to assess safety and tolerability with secondary/exploratory objectives including disc volume, midsagittal disc height and NP water content (T2-time, msec). The analysis of disc height and volume (calculated from sagittal disc heights) was done by experienced radiologists and T2 times were quantified by image analysis experts, all blinded to the treatment allocation. Further, appearance of, or changes in existing Modic changes were evaluated by the radiologists.
Results. Seventeen men and 8 women were included with a mean age of 38±7 years and a mean BMI of 26±4 kg/cm2). Three injected discs were at L3/4, 13 at L4/5 and 9 at L5/S1. Twentyfour discs were Pfirrmann grade 3 and 1 was grade 2. Safety and tolerability were similar to that previously established in DDD patients. Baseline disc volume (mL) in the placebo and STA363 groups was 14.4±3.0 (mean±SD) and 12.6±2.9, respectively. The change at 1, 3 and 6 months was -0.20±0.40, -0.34±0.45 and -0.39±0.54, respectively (placebo), and -0.86±0.98, -1.40±1.15 and -1.53±1.55, respectively (STA363). Baseline disc height (mm) in the placebo and STA363 groups was 11.4±1.3 and 11.1±1.7, respectively. The change at 1, 3 and 6 months was -0.28±0.31, -0.33±0.43 and -0.17±0.37, respectively (placebo), and -0.58±0.92, -1.13±1.06 and -1.27±1.14, respectively (STA363). Changes in disc height and volume were correlated in the STA363 (p=0.03) but not in the placebo group (p>0.05). Mean baseline T2 times (msec) were 72.1±8.2 (placebo) and 83.3±19.3 (STA363). The change at 1, 3 and 6 months was -3.1±4.5, -3.3±6.6 and -4.9±6.3, respectively (placebo), and -7.4±13.0, -10.9±15.5 and -12.1±16.0, respectively (STA363). Existing Modic changes (n=4 (placebo) and n=7 (STA363)) did not change, nor did the prevalence of Modic changes increase.
Discussion. STA363 produces a reduction in disc volume, which is similar to that of other chemonucleolytics with established pain reduction used clinically. Volume decrease is seen after 1 month and seems to stabilize between 3 and 6 months. STA363 does not appear to induce Modic changes. The effects of STA363 on symptoms in LDH patients will be addressed in future studies powered for that purpose.