A Prospective, Randomized, Double-Blinded, Sham-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of IDCT in Subjects With Single-Level, Symptomatic Mild to Moderate Lumbar Intervertebral Disc Degeneration
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 162
- 试验地点
- 29
- 主要终点
- Visual Analogue Scale (VAS) for low back pain
研究概览
简要总结
This is a Phase III, randomized, double-blinded, Sham-controlled, multi-center study in subjects with single-level, symptomatic lumbar (L3- S1) intervertebral disc degeneration. The study will have a 52-week primary period followed by 52 week Follow-up Period (total of 104 weeks).
The study protocol will be approved by the Institutional Review Board (IRB) or Independent Ethics Committee (IEC), and the study will be conducted in accordance with Good Clinical Practice (GCP). All subjects will provide written informed consent prior to Screening.
Approximately 162 subjects will be enrolled in the study. Up to 45 days prior to treatment, subjects will be screened for study inclusion, which includes obtaining baseline MRI and X-ray imaging. Imaging results for subjects initially eligible for study participation will be sent to a central imaging vendor for review and confirmation of eligibility, including the number of levels with degeneration. Subjects meeting all inclusion/exclusion criteria will be assigned to the corresponding treatment arm group and subsequently randomized to IDCT or Sham.
Randomization will occur approximately 7 to 14 days prior to the scheduled treatment administration date.
Overall, 162 subjects will be enrolled and randomized to IDCT or Sham in a 2:1 ratio.
- IDCT (n=108)
- Sham (n=54)
详细描述
Adult subjects with a diagnosis of single-level, mild to moderate, symptomatic lumbar (L3-S1) intervertebral disc degeneration that give consent and meet all the inclusion criteria and none of the exclusion criteria will be enrolled in this study. The disease, single-level disc will be known as the 'target disc' and will be either L3/L4, L4/L5, or L5/S1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
All parties in this trial will be blinded with the exception of the unblinded injecting sub-investigator and their team.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a diagnosis of mild to moderate, symptomatic, single-level degenerative disc disease (DDD) from L3-S
- •Has a target disc that meets Modified Pfirrmann Grade 3-7, as determined by a central radiologist.
- •Is ≥18 and ≤75 years of age, skeletally mature, and has a body mass index (BMI) ≥18 kg/m2 and ≤38 kg/m2 at Screening.
- •Has been experiencing chronic low back pain for at least 6 months prior to Screening.
- •Has had low back pain that is unresponsive to at least 3 months of conservative care (nonoperative treatment) to include at least one non-pharmacological intervention which may include physical therapy, acupuncture, chiropractic manipulation, massage, and at home medically supervised exercise program and two pharmacological interventions which may include NSAIDs, acetaminophen, duloxetine, and/or injectable therapy.
- •Has pre-treatment low back pain score of 45 to 90 on VAS (Visual Analogue Scale) for low back pain at Screening and Day
- •Has pre-treatment ODI score of 35 to 90 at Screening and Day
- •Is willing to voluntarily sign the informed consent form and agrees to the release of previous medical history for purposes of this study (i.e., HIPAA authorization) at Screening.
- •Is physically and mentally able to comply with the protocol, able to understand and complete the required forms, and willing and able to adhere to the requirements of the protocol in the opinion of the Investigator.
- •Female-born subjects of childbearing potential must agree to and comply with using highly effective methods of birth control for the duration of the study (e.g., oral contraceptive, implant, injectable, indwelling intrauterine device, sexual abstinence, condoms, or a vasectomized partner).-
排除标准
- •Physical/ Medical History Exclusion Criteria
- •Has low back pain that in the Investigator's opinion is predominately myofascial in nature.
- •Has constant, unchanging low back pain that is not improved in any spinal position.
- •Has radiculopathy resulting from nerve compression.
- •Has non-radicular unilateral or bilateral leg pain with intensity greater than 50% of the intensity of the low-back pain, as measured by VAS.
- •Leg pain that is of radicular origin, i.e., due to stimulation of nerve roots or dorsal root ganglion of a spinal nerve by compressive forces.
- •Has frequent leg pain that extends below the knee.
- •Has severe unilateral or bilateral osteoarthritis of the knee or hip.
- •Severe spinal arthritis
- •Has cauda equina syndrome.
- •Has had previous lumbar spine surgery.
- •Has had previous disc invasive treatment procedures (i.e., intradiscal electrothermal therapy, intradiscal radiofrequency thermocoagulation) or intradiscal injections (i.e., injection of corticosteroids, methylene blue, dextrose, or glucosamine and chondroitin sulfate) or diagnostic discography at L3-S1 within the 3 months prior to Screening.
- •Subjects who have had basivertebral nerve ablation at L3-S
- •Has clinical suspicion of facet pain as the primary pain generator.
- •Has current infection at the planned procedure site, active systemic infection, or current or prior history of lumbar spinal infection (i.e., discitis, septic arthritis, epidural abscess).
- •Has a history of fibromyalgia.
- •Has tested positive for Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human Immunodeficiency Virus (HIV).
- •Has presence of an active malignancy or tumor, or a prior history of malignancy within the last five years (except for basal cell carcinoma of the skin).
- •Has presence or prior history of a spinal malignancy.
- •Has significant systemic disease, such as unstable angina or autoimmune disease, such as rheumatoid arthritis. Has a history of congenital or acquired coagulopathy or thrombocytopenia.
- •31. Is currently taking anticoagulant, antiplatelet, or thrombolytic medications (except for aspirin or nonsteroidal anti-inflammatory drugs [NSAIDS]) and at the Investigator's medical discernment and discretion is unable to withhold medications for the time required per site standard or care, prior to the IDCT injection or is taking antineoplastic medications.
- •32. Is at higher risk for post-surgical infection (e.g., taking immunosuppressants), has a severe infection or a history of serious infection.
- •33. Has concomitant conditions requiring daily oral steroid usage for more than 30 days in the preceding 90 days before Screening.
- •34. Is taking opioids greater than 20 MME per day on an intermittent (as needed) basis OR is taking 20 MME or greater daily for more than 3 months prior to Screening
- •35. Has a history of unexplained, easy, or persistent bruising or bleeding, bleeding from the gums, or bleeding problems experienced in previous surgical procedures.
- •36. Has a history of hypersensitivity or anaphylactic reaction to bovine products, sodium hyaluronate/ hyaluronan/ hyaluronic acid, gentamicin, amphotericin b, dimethyl sulfoxide (DMSO), crustaceous/ shellfish, or porcine products.
- •37. Has an uncontrolled psychiatric condition or substance/alcohol abuse that would potentially interfere with the subject's participation in the study within 2 years prior to Screening in the opinion of the Investigator.
- •38. Has positive serum pregnancy test or nursing at time of Screening or has plans to become pregnant within the planned length of the study (2 years).
- •39. Has a body habitus that precludes adequate fluoroscopic visualization for the procedure or the procedure is physically impossible.
- •40. Has or requires an implantable electronic defibrillator, pacemaker, or has other contraindication to MRI scanning or cannot tolerate MRI scanning. Subjects who are expected to require a defibrillator or pacemaker, as determined by the Investigator should be excluded.
- •41. Has participated in another clinical study within the 6 months prior to Screening.
- •42. Has been a recipient or plans to be a recipient during trial participation of stem cell product to treat the lumbar spine.
- •43. Has participated in a prior IDCT clinical study.
- •44. Has pending litigation against a health care professional, except where required by the insurer as a condition of coverage.
- •45. A person who would not be available for the entire planned length of the trial.
- •46. Has active or pending worker's compensation claims.
- •In the Investigators opinion, the subject is not suitable for participation in the clinical trial.
- •Imaging Exclusion Criteria:
- •48. Three discs (L3-S1) that have a Modified Pfirrmann Grade 4-
- •49. Has evidence of prior lumbar vertebral body fracture at L3-S
- •50. Has scoliosis with curvature > 10 degrees.
- •51. Has congenital spinal irregularities such as segmentation.
- •52. Has an acute fracture of the spine at the time of enrollment in the study. Clinically compromised vertebral bodies within L3-S1 due to current or past trauma, e.g., sustained pathological fracture or multiple fractures of vertebrae.
- •53. Has evidence of dynamic instability on lumbar flexion extension per screening radiographs as indicated by >4.5 mm of translational motion at L3-S1; >15° of angular motion at L3/-L4; >20° of angular motion at L4-L/5; or >25° angular motion at L5/-S
- •54. Has Grade 2 or higher spondylolisthesis at L3-S1, as assessed by Meyerding classification.
- •55. Has lumbar spondylitis or other undifferentiated spondyloarthropathy.
- •56. Has Modic Type III Changes at L3-S
- •57. Has radiographic evidence or suspicion of a full thickness annular tear at L3-S
- •58. Has evidence of abnormal disc morphology defined as an extrusion or sequestration according to Fardon classification at L3- S
- •59. Has herniation > 3 mm in AP dimension that is associated with nerve root compression.
研究组 & 干预措施
Sham (n=54);
Needle insertion up to the annulus of a single target disc.
干预措施: Sham (No Treatment) (Other)
IDCT (n=108); Intradiscal injection of IDCT in a single target disc
1 mL intradiscal injection of 9,000,000 cells/mL
干预措施: IDCT (rebonuputemcel) (Biological)
结局指标
主要结局
Visual Analogue Scale (VAS) for low back pain
时间窗: Week 52
VAS is a sliding visual scale of 0 being "no pain" and 100 being "worst pain Imaginable' to assess changesfrom baseline in low back pain compared to Sham
Oswestry Disability Index (ODI)
时间窗: Week 52
ODI is a 10-item questionnaire used to measure functional disability in people with low back pain. It is a self-administered tool that assesses how back pain affects daily activities like walking, sleeping, and personal hygiene, with scores ranging from 0% (no disability) to 100% (maximum disability).
Adverse Events
时间窗: Day 1 to Week 52 in each treatment group.
Incidence of grade 2 (moderate) or greater AEs and SAEs
Adverse events of special interest
时间窗: Day 1 to Week 52 in each treatment group
Incidence of Adverse Events of Special Interest (AESI) to include any symptomatic injury of the target disc including annular tear, disc herniation/extrusion/prolapse as well as discitis.
次要结局
- Visual Analogue Scale (VAS)(Week 4, 12 and 26, 78 and 104)
- Oswestry Disability Index (ODI)(Week 4, 12 and 26, 78 and 105)
- EQ-5D(Enrollment through Week 104)
- Disc Volume(Day 1 to Week 104)
- Pain Medication Use(Enrollment to Week 104)
- Concomitant Therapy(Enrollment to Week 104)
- Treatment Failure Rate(Enrollment to week 104)
- Adverse Events(Enrollment to Week 104)
- Adverse Events of Special Interest (AESI)(Enrollment to Week 104)