The Phase 3 C.L.E.A.R.
Clinical Research Study
was conducted with 400 randomized lumbosacral radicular pain/sciatica patients at 40 sites across 25 states in the U.S. and is the largest double-blind randomized controlled Phase 3 epidural steroid injection clinical trial in sciatica. The purpose of the study was to evaluate SP-102 (SEMDEXA™) for the relief of sciatica. SP-102 (SEMDEXA™) is a novel, non-opioid injectable gel formulation intended for the treatment of lumbar radicular pain, commonly known as sciatica.
C.L.E.A.R. (Corticosteroid Lumbar Epidural Analgesia for Radiculopathy)Trial Objectives:
- Primary Objective:
Evaluate the analgesic effect on average daily leg pain (as measured by the NRPS in the affected leg) following a single TF injection of SP-102 (SEMDEXA™) compared to an intramuscular injection of placebo over 4 weeks.
- Secondary Objectives:
Evaluate the degree of disability over time as measured by the ODI
Characterize the change of the subject’s radiculopathy symptoms and overall condition using PainDETECT, BPI-SF, CGIC, and PGIC.
Evaluate the safety of single and repeat SP-102 (SEMDEXA™) TF injections.
The Phase 3 CLEAR trial summary results, which results reflect achievement of primary and majority of secondary endpoints, are as follows:
• For the intent-to-treat (ITT) population, the primary endpoint of change in average daily NPRS pain in the affected leg over 4 weeks following the initial injection of SP-102 demonstrated least square (LS) mean treatment difference (standard error [SE]) of -0.52 (0.163) units [95% confidence interval [CI]: -0.84, -0.20] compared to placebo (P=0.002). The change from baseline to Week 4 in the mean daily average NPRS pain score (standard deviation [SD]) in the affected leg was -1.81 (1.896) for SP-102 versus -1.29 (1.814) in the placebo group. The calculated standardized effect size (Cohen’s D calculated as the group mean difference divided by the pooled standard deviation) associated with the ITT population is 0.28. A statistically significant difference in the mean daily average NPRS pain change between SP-102 and placebo was observed at Week 1 with a mean change from baseline of -1.49 (1.519) for SP-102 and -1.02 (1.472) for placebo (P=0.002), which was maintained through Week 4. These highly significant differences between SP-102 and placebo were also observed following sensitivity analyses for fixed effects.
• Additional analyses were performed with the modified ITT population, i.e., the population with fluroscopically confirmed needle placement. The primary endpoint group mean difference, associated standardized effect size (Cohen’s D), and statistical significance were improved for the mITT population (i.e., -1.08 (0.171), Cohen’s D = 0.68, P<0.001), which was also observed at Week 1 and improved through Week 4. Similarly, the mITT population was observed to have improved and mostly highly statistically significant outcomes for SP-102 over placebo for the secondary efficacy endpoints. In contrast to the ITT population, the mITT population was observed to have statistically significant PainDETECT (a tool to detect neuropathic pain components) for SP-102 over placebo (P=0.037) as well as number of subjects experiencing a 50% reduction in pain in the affected leg (P<0.001).
• For the mITT population, the time to repeat injection (50th quantile [95% CI]) was 99 (78, 129) days for SP-102 versus 57 (49, 67) days for placebo.
• Likewise for the ITT population, most of the secondary endpoints at 4 weeks also demonstrated statistically significant results. For the key secondary endpoint of mean change in in Oswestry Disability Index (ODI) from baseline, the LS mean treatment difference (SE) for SP-102 was -3.38 (1.388) units [95% CI: -6.11, -0.65] compared to placebo (P=0.015). SP-102 treatment resulted in a -8.88 point reduction from baseline, which exceeds the minimal clinically important difference of -8 established in a reported pain study.
• Additional secondary endpoints with statistically significant results for the ITT population include worst pain in affected leg at Week 4 (P=0.004) and over 4 weeks (P=0.001), current pain in the affected leg (P=0.009), average pain in lower back (P=0.035), Brief Pain Inventory-Short Form (BPI-SF) for pain severity (P=0.003) and pain interference (P=0.049), Patient Global Impression of Change (PGIC) (P<0.001) and Clinical Global Impression of Change (CGIC) (P<0.001), proportion of patients achieving a response of 30% (P=0.002).
• The time to repeat injection (50th quantile [95% CI]) for the ITT population was 84 (71, 100) days for SP-102 versus 58 (50, 69) days for placebo (P=0.001).
Results of the Phase 3 C.L.E.A.R. Study
This is the largest prospective, R, DB, placebo-controlled study testing the effect and safety of a corticosteroid:
- Data from the C.L.E.A.R. Trial showed that SP-102 (SEMDEXA™) (dexamethasone viscous gel) is a safe and effective ESI in the treatment of lumbosacral radiculopathy
- SP-102 (SEMDEXA™) showed meaningful pain relief with significantly large differences relative to placebo (p <0.001) for the primary and almost all secondary pain and QOL endpoints over the 4-week primary analysis period
Mean Change From Baseline in NPRS Average Pain Score (Standard Error) in the Affected Leg (ITT Population)
Primary and Secondary Outcomes: NPRS Average Leg Pain In Affected Leg, ODI Total Score, Mean Daily NPRS (worst, current, and lower back), PainDetect, BPI-SF (Change from Baseline to 4 Weeks; ITT Population)
Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change (CGIC) – ITT Population
Responder Analysis (Change from Baseline in Mean NPRS, Average Daily Pain in Affected Leg)1 – ITT Population
