STA363 in the Treatment of Lumbar Disc Herniation

Study Overview
=================
Brief Summary
-----------------
The goal of this clinical trial is to establish safety and tolerability of STA363 injected into a herniated intervertebral disc in patients with sciatica due to disc herniation. The main questions the trial aims to answer are: Is the treatment safe and tolerable? Does the volume of the disc and the herniation decrease? Is sciatica reduced? Participants will be given an injection into the herniated disc of either placebo or STA363 (one dose). Researchers will compare safety, tolerability, effects on disc and herniation volume and on symptoms between the group of patients injected with placebo and the group injected with STA363.

Detailed Description
-----------------
The study will include 24 patients, recruited at 4 different sites, suffering from radiculopathy due to lumbar disc herniation (LDH). Patients will be screened for symptoms, disease history and magnetic resonance imaging (MRI) evidence of LDH. Baseline data (e.g. pain recording and MRI data) will be collected, and 1/3 of the patients will then be randomized to intradiscal injection with placebo (Omnipaque with water for injection, 1.5 mL) and 2/3 of the patients will be randomized to STA363 (lactic acid, 120 mg/mL with Omnipaque, 1.5 mL). The injections will be done using fluoroscopic guidance, and the patients will be treated with intravenous antibiotics and sedatives. The first follow-up will be done by phone 1 week after the treatment, while the other follow-ups will be physical visits at month 1, 3 and 6 at the site. In conjunction with the visits, the patient will record daily pain intensity (Numerical Rating Scale) for 7 days using an eDiary, and MRI will be performed. The primary completion time i 6 months with the primary objectives safety and tolerability. Important secondary objectives will be changes of disc volume and pain.

Official Title
-----------------
A Prospective, Randomised, Double-blinded, Placebo-controlled Study Investigating the Safety and Tolerability of STA363 in Patients With Radiculopathy Caused by Lumbar Disc Herniation

Conditions
-----------------
Lumbar Disc Herniation

Intervention / Treatment
-----------------
* Drug: Lactic Acid
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent prior to any study-related procedures Patient has a single subligamentous posteriolateral lumbar disc herniation (protrusion or extrusion) of any lumbar disc below L1/L2 diagnosed by clinical symptoms and/or physical findings and confirmed by MRI Patient has symptoms and/or physical findings consistent with a unilateral radiculopathy affecting one nerve root (L2-L5) Patient has leg pain of the dermatome consistent with the nerve root affected by the herniation The herniated disc is 3 or lower on the Pfirrmann scale (grade 1-5) Patient has experienced symptoms of a herniated disc for at least 6 weeks prior to randomisation without sufficient relief with pain medications and other conservative therapies Ability to understand the written and verbal information about the study Male and female patients 18 years or older but 50 years or younger Women of childbearing potential eligible if using effective contraceptives Patient has a body mass index (BMI) of ≥18 to ≤35 kg/m2 Patients who meet all the following NRS selection criteria for radicular leg pain: Presence of at least 5 pain NRS assessments (entries) for 7 consecutive days NRS daily pain scores between 3-9 Not more than 2 NRS scores of 3 Exclusion criteria: Treatment with any investigational product within 3 months prior to the screening visit Patient has a sequestered lumbar disc herniation or transligamentous/ herniation confirmed by MRI Patient has a bulging disc Patient has experienced symptoms of lumbar disc herniation for more than 6 months Patient has 2 or more symptomatic lumbar disc herniations (presence of non-symptomatic herniations in addition to the symptomatic herniation is allowed) Patient has cauda equina syndrome Previous intradiscal therapeutic intervention of the index disc or has had any lumbar spine surgery Presence of lumbar spine disease and/or clinically significant deformity other than a lumbar disc herniation which, in the opinion of the investigator, will affect evaluation of safety and/or efficacy Untreated, ongoing active infection and/or discitis Current infection or prior history of spinal infection (e.g., discitis, septic arthritis, epidural abscess) or an active systemic infection. Evidence of prior lumbar vertebral body fracture or trauma. Spondylolisthesis or retrolisthesis grade 2 and above or spondylolysis at the index or adjacent level(s). Lumbar spondylitis or other undifferentiated spondyloarthropathy affecting the index disc. Patients previously included in the study. Patients suffering from psychosomatic pain in the opinion of the Investigator. Patients requiring continuous treatment with warfarin or other anticoagulant therapy. Known alcohol and/or drug abuse. Pregnant or lactating females, or intention to become pregnant within the study period. Known allergy or intolerance to the contrast agent Omnipaque®. Known opioid allergy or intolerance. Any other condition that, in the opinion of the Investigator, precludes the patient from taking part in this study. Any specific contraindication for MRI such as claustrophobia, intracranial clips or pacemakers.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>1.5 mL of Omnipaque mixed with water for injection | Drug: Placebo<br>* 1.5 mL of Omnipaque in water for injection will be slowly injected into a symptom-generating herniated lumbar disc<br>|
| Experimental: STA363<br>1.5 mL of STA363 (lactic acid, 120 mg/mL) mixed with Omnipaque | Drug: Lactic Acid<br>* 180 mg of STA363 will be slowly injected into a symptom-generating herniated lumbar disc<br>* Other names: STA363;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | Safety and tolerability will be measured using the following outcomes: Incidence and nature of adverse events (AEs) Changes in physical examination findings blood pressure and heart rate 12-lead electrocardiogram Hematology and clinical chemistry Pain intensity at the injection site during and 15 minutes after injection (numerical rating scale; NRS). NRS is reported on a 0-10 scale where 0 represents No pain and 10 Worst imaginable pain Other aspects of intervertebral disc morphology (IVD) morphology from baseline (e.g., Modic changes) | Baseline and 1 week and 1,3 and 6 months after intervention for all outcomes except changes in IVD morphology (time frame 1, 3 and 6 months after intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disc volume | Volume will be measured by MRI | Baseline and 1,3 and 6 months after intervention | 
| Disc height | Height will be measured by MRI | Baseline and 1,3 and 6 months after intervention | 
| Radicular leg pain | Leg pain will be reported by the patients using an NRS. (minimum value: 0; maximum value: 10) for 7 consecutive days. Lower scores means a better outcome. | Baseline and 1 week and 1,3 and 6 months after intervention | 
| Patient Global Impression of Change (PGIC) | PGIC will be reported by the patients using an electronic device | Baseline and 1 week and 1,3 and 6 months after intervention | 
| Disc intensity | The intensity of the disc will be measured using T2-weighted MRI | Baseline and 1,3 and 6 months after intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lumbar radiculopathy