Up to 84% of adults of low back pain sometime in their lives and over 1 in 4 of the US adult reports recent history of (in the last 3 months) low back pain. Low back pain is costly: Total US healthcare expenditure for low back pain in 1998 were estimated at $ 90 billion.
Ref: AHRQ Publication No. 16-EHC004-EF February 2016.
This is a Phase I, first in human, randomized, double blind, vehicle and placebo-controlled, parallel group, multi-center study in subjects with single level, symptomatic lumbar intervertebral disc degeneration (>6 months) and unresponsive to conservative therapy for at least 3 months. The study will compare single intradiscal injections of high and low dose IDCT with two control groups (saline, Sodium Hyaluronate).
7 study visits will be completed by all subjects; screening, day 1 (injection day), week 4, week 12, week 26, week 72 and week 104. The subject will be assessed for safety and efficacy utilizing VAS and ODI questionnaires alongside radiographic evaluations. The study will have a 1 year follow-up and a 1 year extension period (total 2 years).
The subject must have:
1. Diagnosis of early to moderate degenerative disc disease (DDD), Modified Pfirrmann Grade 3-7.
2. Chronic low back pain for at least 6 months prior to screening; unresponsive to at least 3 months of conservative care.
2. Low back pain of 40 to 90 mm on the VAS and ODI score of 30 to 90.
The subject is excluded if he/she has:
1. Symptomatic involvement of more than one lumbar disc.
2. Other persistent pain/nerve issues including, for example, radiculopathy, leg pain, cauda equine syndrome, etc.
3. Fracture of the spine, previous lumbar spine surgery or previous treatment of the target disc.
4. Evidence of dynamic instability on lumbar flexion extension radiographs.
5. Grade 2 or higher spondylolisthesis at the target disc, lumbar spondylitis or other undifferentiated spondyloarthropathy, or Type III Modic changes around the target disc.
6. Clinical suspicion of a full thickness annular tear at the target disc or other abnormal disc morphology.
7. Clinical suspicion of facet pain as primary pain generator.
8. Subjects who test positive for communicable disease, have significant systemic disease, or are prone to infection.
9. Patient who are deemed unsuitable for clinical study participation by the investigator.
IDCT is a mixture of allogeneic progenitor cells known as diskogenic cells and a viscous delivery vehicle. The cells are frozen to cryogenic temperature until immediately prior to dosing, when they are thawed, mixed with the viscous vehicle, and delivered into the subject. The vehicle is composed of sodium hyaluronic solution and experience.
The active ingredient of IDCT is a live cell population known as diskogenic cells which are human progenitor cells generated from adult intervertebral disk tissue. The diskogenic cells are created through a multistep process that results in significant proliferation and phenotypic changes to the cells. At the completion of the manufacturing process, the diskogenic cells are subjected to extensive testing prior to use, including identity, purity, potency and safety evaluations.
Since 2007, the diskogenic cells have been generated successfully from 23 donors. In the animal studies no test article related toxicity or safety concerns have been identified at human doses as well as higher than human doses. Diskogenic cells are multipotent for mesenchymal lineages including having a strong chondrogenic potential. Endogenously, the cells generate proteoglycan and collagen which are the extracellular matrix molecule that make up the intervertebral disk. New matrix generation is one the proposed mechanism of action for IDCT. These cells are hypo-immunogenic.
Diskogenic cells lacked expression of costimulatory molecules CD40, CDE AT and CD 86 required for effective T cell induction. IDCTs have MHC class I positive (ABC) and MHC II negative (HLA-DR/DP/DQ). In addition to this it generates an anti-inflammatory local milieu. Therefore it has dual mechanism of action that includes matrix formation and anti-inflammatory signaling that is likely to cause improvement to human degenerative disk disease upon delivery. The cells do not have the propensity to form tumors and are hypo-immunogenic.