Lumbar disc herniation MedDRA version: 17.1 Level: PT Classification code 10050296 Term: Intervertebral disc protrusion System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: SI-6603 for Injection
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Condoliase
CAS Number: 9024-13-9
Current Sponsor code: SI-6603
Other descriptive n
Sponsors
Seikagaku Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients who have given their written informed consent to participate in a clinical study based on voluntary agreement after a thorough explanation of the patient´s participation is provided to them. Patients must have adequate reading and writing abilities such that they can comprehend and answer the questions on the patient-completed assessments and Informed Consent Form (ICF). 2. Patients with lumbar disc herniation (L1-L2, L2-L3, L3-L4, L4-L5, or L5-S1) "protrusion type" or "extrusion type" in the posterior lateral or central location as assessed by MRI and clinical symptoms corresponding to the level of the impaired nerve root; if the sixth lumbar vertebra (L6) is present, patients with impaired L5 or S1 nerve root and corresponding clinical symptoms 3. Patients with positive FNS /=30 mm) during the past 24 hours at the time of informed consent. 7. Male or female patients 30 to 70 years of age at the time of informed consent 8. Female patients are not pregnant and do not plan to become pregnant during the study. Females of childbearing potential must provide a negative serum pregnancy test during the Screening period, must be using reliable contraception, and must continue to use reliable contraception until end of study (reliable methods of contraception are defined in exclusion criterion #6 below). Non-childbearing potential is defined as postmenopausal for at least 2 years or surgical sterilization or hysterectomy at least 3 months before study start. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 800 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: 1. Patients who have 2 lumbar disc herniations as assessed by MRI 2. Patients with a contraindication to receiving an MRI 3. Patients in whom a rupture into the posterior longitudinal ligament as assessed by MRI shows sequestration (free fragment) type lumbar disc herniation. Transligamentous extrusion type of disc herniation is allowed. 4. Patients who previously received SI-6603 administration at any time 5. Patients who are pregnant, breast-feeding or women of childbearing potential with positive pregnancy tests. Female patients with posthysterectomy and/or bilateral tubal ligation or postmenopausal who have not menstruated within past 2 years do not need to take the pregnancy tests. 6. Sexually active female patients of childbearing potential who are not willing to use adequate contraceptive measures to avoid pregnancy until end of the study. Sexually active male patients who are not willing to use adequate contraceptive measures until end of the study. Adequate methods of birth control include the following: -- Hormonal contraception (female patients) or use of at least one acceptable double-barrier method Acceptable double-barrier methods include the following: ------diaphragm plus a spermicidal agent -------condoms (male or female) plus a spermicidal agent - Vasectomy, intrauterine device, and/or exclusive sexual partner for whom one of the above acceptable methods applies 7. Patients who have undergone lumbar operation, lumbar percutaneous nucleotomy or lumbar intradiscal therapies (e.g., chemonucleolysis or intradiscal electrothermal treatment) under any of the following conditions: - At the affected level of lumbar disc herniation - Within the last 2 years at any lumbar spine level other than affected level - With symptoms not completely improved by the above procedure at any lumbar spine level other than affected level 8. Patients with the following medical conditions or diseases: -Vertebral body angle formed by flexion >/=5° -Neurological disorders including cauda equina syndrome that is severe or that demonstrates rapid progression. -Spondylosis deformans, spondylolisthesis (translation of vertebral body >/=3 mm), spinal deformity, spinal canal stenosis (except for complication of lumbar disc herniation), spinal tumor, ankylosing spondylitis, diskitis, or clinically significant disorders of the lumbar spine other than disc herniation. - Osteophyte at lumbar spine (Nathan's classification >/=3rd degree) - Cancer: patients who have cancer or a past history of any cancer within 5 years prior to the time of informed consent, with the exception of basal cell or squamous cell carcinoma of the skin curatively treated or localized gynecologic cancer treated by total hysterectomy. - Human immunodeficiency virus (HIV) infection or a clinically significant infection - A clinically significant disorder such as cerebrovascular disease, pulmonary infarction, ischemic heart disease, cardiac dysrhythmia, myocardial infarction, or congestive heart failure - Chronic diseases such as osteoporosis, rheumatoid arthritis, uncontrolled diabetes mellitus, uncontrolled pulmonary disease (asthma), or uncontrolled hypertension - Patients who have evidence of major psychiatric disease, mental disorder, drug dependency, alcohol dependency, or substance use disorders. - Patients who have a tendency to bleed. 9. Patients with medical conditions and/or diseases that the Investigator believes could affect the study results or the safe conduct of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary study objective is to evaluate the safety of a single-dose intervertebral disc injection of SI-6603 at a dose of 1.25 U in patients with lumbar disc herniation, for a 13-week follow-up period.;Secondary Objective: The secondary study objective is to evaluate the efficacy of a single-dose intervertebral disc injection of SI-6603 at a dose of 1.25 U in patients with lumbar disc herniation, for a 13-week follow-up period.;Primary end point(s): The following safety endpoints will be assessed: - Occurrences of AEs - Stability evaluation of vertebral bodies by X-ray at the times specified in the schedule of events ---Translation of vertebral body ---Vertebral body angle formed by flexion - Changes from baseline in disc height (disc index) assessed by X-ray at the times specified in the schedule of events - Changes of disc degeneration, vertebral body endplates, and adjacent bone marrow assessed by MRI at the times specified in the schedule of events -----Modic classification -----Pfirrmann classification - Clinically significant change in vital signs at the times specified in the schedule of events - Clinically significant change in clinical laboratory tests at the times specified in the schedule of events - Serum anti-SI-6603 IgE antibody and IgG antibody titer at the times specified in the schedule of events - Occurrence of post-treatment lumbar surgery other than surgery for lumbar disc herniation at the same level of the investigational drug administration;Timepoint(s) of evaluation of this end point: End of trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The following secondary efficacy endpoints will be assessed at the times specified in the schedule of events and overall time-course, and changes from baseline will be analyzed: - Worst leg pain during the past 24 hours assessed by VAS. - Worst back pain during the past 24 hours assessed by VAS. Functional disability measured by the Oswestry Disability Index (ODI). - Change of neurological status from baseline determined by neurological examinations: -----Femoral Nerve Stretching (FNS) test for patients with lumbar disc herniation L1-L2, L2-L3, or L3-L4 or -----Straight Leg Raising (SLR) test [for patients with lumbar disc herniation L4-L5 or L5-S1, and -----Sensation, muscle strength, and deep tendon reflex. - Occurrence of post-treatment surgery for lumbar disc herniation at the same level of administration of the investigational drug up to Week 13 including patients who discontinued from the study.;Timepoint(s) of evaluation of this end point: End of trial | — |
Countries
Germany, Italy, Spain, United States
Contacts
Public ContactClinical Development Department
Seikagaku Corporation
Outcome results
None listed