This is a research study of SP-102, an experimental medication designed to relieve pain in patients with moderate to severe sciatica (pain in the lower back, hips, buttocks and legs). SP-102, placebo (a medication that looks like SP-102 but does not contain any active ingredient), or an active comparator (dexamethasone sodium phosphate) is given once by the participant's healthcare professional. If a participant meets qualifications, each participant will have the option of receiving one supplemental open-label injection of SP-102, greater than four weeks and up to twenty weeks after their first injection.

The purpose of the study is to measure how well a single injection of the experimental medication, SP-102, relieves pain versus placebo. The study will also measure how well SP-102 relieves pain versus an active comparator medication (dexamethasone sodium phosphate). The study will also investigate the side effects of SP-102.

This is a double-blind, randomized, active comparator (dexamethasone sodium phosphate) and placebo-controlled, multicenter trial in participants with moderate-to-severe lumbosacral radicular pain evaluating the safety and efficacy of a single SP-102 TF injection compared to a single placebo IM injection or a single dexamethasone sodium phosphate TF injection (active comparator), followed by an open-label safety extension, evaluating an optional SP-102 TF injection, if indicated and qualified for, administered once between > 4 to 20 weeks later.

Inclusion Criteria:

Main Inclusion Criteria:

• Able and willing to read, write, and understand the English language and provide English language written informed consent prior to beginning any study procedures.
• Age 18 to 75 years (inclusive) at the Screening Visit.
• A diagnosis of lumbosacral radicular pain (sciatica) present for at least 6 weeks and not more than 9 months prior to the Screening Visit.
• Clinical symptoms consistent with the imaging (MRI)
• Agrees to follow study-specific medication requirements.
• If sexually active and a female of child-bearing potential or a male capable of bearing a child, agrees to use an effective method of birth control during the study.
• Has reviewed all study specific materials and has, in the opinion of the Investigator, the abilities to understand and appropriately complete all study procedures.

Day 1 Inclusion:

As calculated by the eDiary system, during the 7 days (D-7 to D-1) immediately prior to the Baseline Visit, the participant:

1. Completed the current, worst, and daily average NPRS scores (in the affected leg, non-affected leg, and lower back) in the eDiary on at least 6 out of the 7 days during the Baseline Period.
2. Meets the NPRS average daily pain score criteria,
3. Has a mean (at Baseline Visit) NPRS worst pain score in the affected leg that is greater than the mean worst pain score in lower back.

Participant continues to demonstrate a clear understanding of how to complete the eDiary.

Participant remains an appropriate candidate for trial participation in the opinion of the Investigator.

Participant continues to meet all the screening inclusion criteria and none of the exclusion criteria. -

Exclusion Criteria:

• Has a body mass index ≥40 kg/m2.
• Has radiologic evidence of a condition that would compromise study outcomes:

Spinal cord tumor (intra- or extradural) or hematoma. Epidural or intrathecal abscess. Systemic infection.

• Has ever had lumbosacral back surgery or plans to undergo spine surgical intervention while in the study.
• Has been diagnosed with insulin dependent diabetes mellitus.
• Presence of any other disorder, condition or circumstance (including secondary gain) that, in the opinion of the Investigator, has the potential to prevent study completion and/or to have a confounding effect on outcome assessments.
• Use of any investigational drug and/or device within 30 days, or is scheduled to receive an investigational drug other than blinded study drug during this study.
• Has any contradiction to performing MRI (such as coronary pacemakers and implantable cardioverter-defibrillators [ICDs], metallic foreign bodies, neuro and spinal cord stimulators).
• Has history of malignancy or evidence of malignancy, within 5 years of Screening Visit.
• Has significant motor impairment
• Has regular use of opioid doses > 30 mg morphine equivalents per day for more than 2 days per week in the 30 days prior to the Screening Visit.
• Involvement in an ongoing worker's compensation claim, disability claim, or litigation related to any pain problem, receiving payments for a settled claim, awaiting pending payment for a settled claim, or any potential secondary gain in the opinion of the Investigator.