Corticosteroid Lumbar Epidural Analgesia for Radicular Pain 2 (CLEAR 2)

Corticosteroid Lumbar Epidural Analgesia for Radicular Pain (C.L.E.A.R) 2 - A Randomized, Double-blind, Active Comparator and Placebo-controlled, Multicenter, Safety and Efficacy Trial of SP-102

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Lumbosacral Radicular Pain
• Intervention / Treatment: Drug: SP-102; Drug: Placebo; Drug: Dexamethasone Sodium Phosphate 10 MG/ML

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 755
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Senior Director Clinical Operations; Phone Number: 1-650-386-6709; Email: clinicaltrials@semnurpharma.com
• Study Contact Backup: Name: Dmitri Lissin, Study Director, MD; Phone Number: 1-650-422-7515

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Comparator	Drug: Placebo; One injection
Experimental: SP-102	Drug: SP-102; One Injection
Active Comparator: dexamethasone sodium phosphate	Drug: Dexamethasone Sodium Phosphate 10 MG/ML; One injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline to W4 in the mean NPRS average daily pain score.	The Numeric Pain Rating Scale (NPRS) is a self-reported scale assessing average pain intensity over the past 24 hours in the affected leg. Possible scores range from 0-10 (0 is no pain, 10 is worst pain imaginable) Change from baseline (mean of the scores recorded on the 7 days [D-7 to D-1] immediately prior to the P1 Injection Day) in mean NPRS average daily pain score in the affected leg over 4 weeks (i.e., W1, W2, W3, W4) for SP-102 versus placebo.	Day 1 to week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in ODI total score	The Oswestry disability index (ODI) is a validated, self-reported instrument that evaluates degree of disability (0-100, 0=No disability, 100=Maximum disability). Comparison is between SP-102 and placebo.	Day 1 to Week 4
Patient Global Impression of Change	The PGIC scores range from 1 (very much improved) through 7 (very much worse) as assessed by the participant.	Day 1 to week 4
Mean change in BPI-Pain Interference (BPI-PI) score from P1 Baseline (D1) to P1 W4 for SP-102 versus placebo.	Participants rate their worst, least, average, and current pain intensity on a 0-10 numeric rating scale as it affects their daily functioning (0=does not interfere and 10=completely interferes).	Day 1 to week 4
Proportion of participants with a ≥ 30% improvement from P1 D1 to W4 in mean NPRS average daily pain score in the affected leg for SP-102 versus placebo.	The Numeric Pain Rating Scale (NPRS) is a self-reported scale assessing average pain intensity over the past 24 hours in the affected leg. Possible scores range from 0-10 (0 is no pain, 10 is worst pain imaginable) Change from baseline (mean of the scores recorded on the 7 days [D-7 to D-1] immediately prior to the P1 Injection Day) in mean NPRS average daily pain score in the affected leg over 4 weeks (i.e., W1, W2, W3, W4) for SP-102 versus placebo.	Day 1 to week 4
Proportion of participants with a ≥ 50% improvement from P1 D1 to W4 in mean NPRS average daily pain score in the affected leg for SP-102 versus placebo.	The Numeric Pain Rating Scale (NPRS) is a self-reported scale assessing average pain intensity over the past 24 hours in the affected leg. Possible scores range from 0-10 (0 is no pain, 10 is worst pain imaginable) Change from baseline (mean of the scores recorded on the 7 days [D-7 to D-1] immediately prior to the P1 Injection Day) in mean NPRS average daily pain score in the affected leg over 4 weeks (i.e., W1, W2, W3, W4) for SP-102 versus placebo.	Day 1 to week 4

Collaborators and Investigators

• Sponsor: Semnur Pharmaceuticals, Inc.
• Collaborators: Cromos Pharma LLC; Syngene

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: May 6, 2026
• First Submitted That Met QC Criteria: May 6, 2026
• First Posted (Actual): May 12, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Sciatica; Leg Pain; Lumbosacral Radicular Pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Mononeuropathies; Sciatic Neuropathy; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Sciatica; dexamethasone 21-phosphate
• Other Study ID Numbers: SP-102-05

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No