SKK

Study Contact:

Christiana Booher 434-243-0296

IRB-HSR 19403

Clinic Visit Registration: 21136-Hassanzadeh

Inclusion Criteria

• Did the subject sign the most current IRB-approved written informed consent?
• Is the subject a male or female aged 30 to 70 years (inclusive) at the time of informed consent?
• Does the subject have a contained posterolateral Lumbar Disc Herniation (LDH) at either L4-L5 or L5-S1 (or L5-L6)?
• Subject has symptoms of radiculopathy and/or radicular leg pain in the unilateral leg corresponding to the distribution of the affected nerve root for 6wks or more but 1 yr or less, and still ocurring at time of consent
• Presence of demonstrable nerve root impingement, as assessed by MRI
• Chief complaint of unilateral radiculopathy and/or radicular leg pain corresponding to the ipsilateral leg and distribution of the affected nerve root
• A positive result of Straight Leg Raise (SLR) test (≤70°) only on the ipsilateral leg having chief complaint of radiculopathy that corresponds to the pain and distribution of the affected nerve root
• Inadequate improvement in pain caused by LDH despite 6 weeks or more of conservative treatment*? *Conservative treatment must be pharmacotherapy (e.g., steroids, NSAIDs, or non-opioid analgesics). Physical therapy, chiropractic, acupuncture, spinal injection, epidural injection, ornerve block can be used only in combination with pharmacotherapy
• Conservative treatment ongoing at the time of Informed Consent
• For 7 consecutive days up to the day before randomization, did the subject record at least 5 worst leg pain scores without using any rescue medication OR increasing OR adding restricted concomitant medications? ***[VERIFIED ON SUBJECT’S EDIARY AND/OR ELIGIBILITY REPORT IN TRIAL MANAGER]
• For 7 consecutive days up to the day before randomization, is the average worst leg pain score between 50 and 90 mm? ***[VERIFIED ON SUBJECT’S EDIARY AND/OR ELIGIBILITY REPORT IN TRIAL MANAGER]
• For 7 consecutive days up to the day before randomization, is the range of fluctuation in worst leg pain scores ≤ 25 mm? ***[VERIFIED ON SUBJECT’S EDIARY AND/OR ELIGIBILITY REPORT IN TRIAL MANAGER]
• Subject is willing to comply with the rules of concomitant medications (listed in Section 6.6) and concomitant therapies (listed in Section 6.7) of the protocol
• Subject is willing to comply with the rules of rescue medication (listed in Section 6.6.3) of the protocol
• The Subject scored ≥ 30% on the ODI at the time of randomization [VERIFIED ON TRIALMAX SLATE AND/OR ELIGIBILITY REPORT IN TRIAL MANAGER]

Exclusion Criteria

• Body mass index(BMI) ≥35
• Receiving compensation according to the Workers’ Compensation Act
• Currently has dominant low back pain compared to radicular leg pain
• Has any clinically significant disorders such as: • Uncontrolled pulmonary disease • Asthma • Chronic obstructive pulmonary disease (COPD) • Uncontrolled hypertension • Type I Diabetes • Uncontrolled Type II Diabetes • Any other serious heart, liver, kidney, or blood disease or immunodeficiency
• Has LDHs with clear impingement to the nerve root at 2 or more levels with symptoms corresponding to the distribution of the affected nerve root
• Has any of the following history, diagnosis, sign, or symptom of any disorder that would interfere with the pain efficacy assessments • Chronic pain disorders • Fibromyalgia • Restless leg syndrome • Peripheral neuropathy caused by certain disorders (e.g. diabetes) • Parkinson’s disease • Complex regional pain syndrome • Osteoarthritis (unless symptoms are only in the upper extremities) • Osteoporosis • Spondyloarthritis • Ankylosing spondylitis • Rheumatoid arthritis • Gout
• Has cancer or a past history of any cancer within 5 years prior to the time of informed consent? ***NOTE: basal cell or squamous cell carcinoma of the skin curatively treated or localized gynecologic cancer treated by total hysterectomy are permitted.
• History or signs of coronary artery disease with or without angina pectoris or myocardial infarction within the last 6 months
• Takes (on average) more than 2 doses per week of immediate release opioids
• Use of cannabis for relief of pain
• History of substance abuse or dependency within the last 5 years. ***NOTE: This includes alcohol, opioids, cannabis (even where legal), and prescribed Central Nervous System (CNS) stimulants or depressants
• A contraindication to receive MRIs? (e.g., pacemaker or other metallic implants not compatible with MRI)
• A rupture into the posterior longitudinal ligament for the LDH in the disc to be treated.(i.e., (those with transligamentous extrusion or sequestration [free fragment]-type LDH)
• A presence of isolated central herniation for the LDH in the disc to be treated
• A presence of anterolateral herniation for the LDH in the disc to be treated
• A presence of extraforaminal herniation for the LDH in the disc to be treated
• Clinical symptoms of radiculopathy (sciatica, weakness, or sensory loss) caused by LDH on the contralateral leg
• Has received a block procedure for the treatment of LDH in the past 35 days prior to RANDOMIZATION? (e.g., spinal injection, epidural injection, or nerve block)
• Has received oral or injectable corticosteroids in the past 35 days prior to RANDOMIZATION? NOTE: Inhaled, nasal, or topical steroids used over small areas of skin (e.g., < 100 cm2)
• Has taken opioids by any route of administration within 10 days prior to RANDOMIZATION
• Has used cannabis by any route of administration within 10 days prior to RANDOMIZATION
• Has received local anesthesia to the back, buttock, or posterior/lateral aspects of the affected leg within 10 days prior to RANDOMIZATION **NOTE: If the local anesthesia was part of a block procedure, Exclusion Criterion # 5 applies
• Currently has low back pain caused by disorders other than LDH
• Low back pain continued for more than 3 months at the time of the onset of the current radicular leg pain
• Subject’s average low back pain greater than the average leg pain for 7 consecutive days up to the day before RANDOMIZATION? ***[VERIFIED ON SUBJECT’S EDIARY AND/OR ELIGIBILITY REPORT IN TRIAL MANAGER]
• Pregnant or breast-feeding
• Subject is of childbearing potential with a positive SERUM pregnancy test ***NOTE: Pregnancy tests will not be required for female subjects who have undergone a hysterectomy and/or bilateral tubal ligation, or who are postmenopausal (have not menstruated within the past 2 years
• Subject is of childbearing potential with a positive URINE pregnancy test ***NOTE: Pregnancy tests will not be required for female subjects who have undergone a hysterectomy and/or bilateral tubal ligation, or who are postmenopausal (have not menstruated within the past 2 years)
• Subject is a sexually active female of childbearing potential with a male partner who is NOT willing to use adequate contraceptive measures to avoid pregnancy until the end of the study? ***NOTE: Female subjects who have undergone hysterectomy and/or bilateral tubal ligation, or are postmenopausal (have not menstruated within past 2 years) do not need to practice birth control.
• Subject is a sexually active male with a female partner who is NOT willing to use adequate contraceptive measures to avoid pregnancy until Week 13
• Has had a lumbar operation, lumbar percutaneous nucleotomy, or lumbar intradiscal therapy at any level of the lumbar spine
• Has an X-ray image finding of vertebral body angle formed by flexion ≥ 5° and/or spondylolisthesis (vertebral body translation ≥ 3mm) in the disc to be treated
• Has any of the following spinal related disorders: • Spondylosis deformans • Degenerative spondylolisthesis • Spinal deformity • Scoliosis: Cobb angle >10° • Lordosis [L1-S1]: Cobb angle <35° • Spinal tumor • Diskitis • Vertebral fracture adjacent to the disc to be treated • Bony stenosis with nerve root impingement at L3-L4, L4-L5, or L5-S1 • Severe lumbar degenerative disc disease (in the disc to be treated)
• Does the subject have any of the following spinal related disorders associated with low back pain that would interfere with safety or efficacy evaluations: • Spinal canal stenosis • Spondyloarthritis • Ankylosing spondylitis • Vertebral fracture in the lumbar spine • Significant degenerative disease of the facet joints • Any other disorders of the lumbar spine associated with low back pain that would interfere with safety or efficacy evaluations
• Osteophytes in the lumbar spine (Nathan’s classification ≥3rd degree)
• A history of psychosis or psychotic disorder (including schizophrenia and bipolar I disorder)
• A history of any nonpsychotic psychiatric disorders (including known personality disorders) that have been sufficiently severe to cause functional impairment within 6 months prior to screening
• Consumes more than an average of 2 units of alcohol per day? ***NOTE: 1 unit = 12 oz. of beer, 5 oz. of non-fortified wine, or 1.5 oz. of 80-proof liquor
• Has taken extended or controlled release opioids in the past 6 months
• Does not agree or is the subject unlikely to remain free of prohibited medications during the course of the trial
• Tested positive at screening for drugs of abuse? **NOTE: A positive result for benzodiazepine may be permissible if, in the investigator’s opinion, is the result of appropriate use of a prescribed medication. **NOTE: Positive urine drug tests are considered conclusive and may not be repeated
• Tested positive at RANDOMIZATION for drugs of abuse?**NOTE: A positive result for benzodiazepine may be permissible if, in the investigator’s opinion, is the result of appropriate use of a prescribed medication. **NOTE: Positive urine drug tests are considered conclusive and may not be repeated
• Tested positive on the blood alcohol test at screening? ***NOTE: A positive blood alcohol test cannot be repeated
• A history of any neurologic disorders (including cauda equina) that are severe or that demonstrate rapid progression
• Has experienced a seizure in the past 5 years
• Is currently taking anticonvulsant medications for any reason other than neuropathic pain
• Has motor weakness graded less than 4 on the Medical Research Council Scale
• A history of human immunodeficiency virus (HIV) or a current, active, clinically significant systemic infection requiring treatment with antibiotics, antivirals, or antifungals
• Has clinically evident: • cerebrovascular disease • pulmonary infarction • congestive heart failure • arrhythmia (excluding normal sinus rate variations and atrial or ventricular ectopy ≤2/min).
• Has difficulty receiving injections of investigational product
• Has a tendency to bleed or have any bleeding disorders such as (but not limited to): • hemophilia • aplastic anemia • cirrhosis of the liver • leukemia • thrombocytopenia • vitamin K deficiency
• Is using medication for the purpose of anticoagulation (including heparin and warfarin) which cannot be reversed preoperatively
• Has medical conditions and/or diseases that the investigator believes could affect the study results or interfere with safe conduct of the study
• Has an Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5x upper limit of normal (ULN)
• Total bilirubin ≥1.5 x ULN? ***NOTE: isolated Gilbert’s syndrome is permitted
• Serum creatinine ≥1.5 x ULN
• Tested positive for hepatitis C virus antibodies or hepatitis B surface antigen?***NOTE: Subjects who have been successfully treated for hepatitis C and currently have undetectable HCV RNA are eligible for study participation
• Difficulties securing an investigational product injection route by the investigator for anatomical reasons
• Currently hospitalized or has a planned hospitalization during the life of the study
• Has a planned move that may result in difficulty visiting the clinical site(s) during the life of the study
• Previously participated in a clinical study of SI-6603
• Is involved in personal injury litigation due to a lumbar-related injury
• Has participated in another interventional clinical study within 120 days prior to the time of informed consent or expected to participate in another study during the period of this study

Study Summary

• Screening Visit: Consent, inclusion/exclusion
• Surgery: Randomization/ Treatment
• Follow-Ups: Visits 3-9
• Discontinuation visit: Visit 10

Payment

$100 per visit (10 total visits)

Covered Expenses

All research related procedures for this study (MRI, labs, etc) will be paid for by the sponsor