Institutional Review Board, Hospital for Special Surgery
April 19, 2011
The safety of study participants is our top priority. The trial is approved and periodically reviewed by an Institutional Review Board (IRB), which includes doctors, administrators, ethicists, and members of the general public. The safety of clinical trials is reviewed by the U.S. Food and Drug Administration.
Before enrolling in a clinical trial, the investigator will explain the purpose of the trial, its expected benefits, any possible risks or side effects, and what your role will be. This is the time to ask questions! If you want to join the trial, you must sign the informed consent documents. You can leave a clinical trial at any time without penalty.
For further information, see Understanding Clinical Trials.
The purpose of this study is to test the safety and performance of an investigational drug called Intradiscal rhGDF-5 as an injectable treatment for degenerative disc disease. Degenerative disc disease is a medical condition which causes your disc (the tissue between the vertebrae in your spine) to wear away and cause pain in your lower back. Investigational means that rhGDF-5 has not been approved by the U.S. Food and Drug Administration (FDA).
Intradiscal rhGDF-5 is a “recombinant growth and differentiation factor”. Growth factors help in the growth of tissue and cells. Since rhGDF-5 is a general growth factor, it has the potential to grow the same type of tissues as where it is applied (bone or disc). Based on early testing in animals, direct injection of the study drug into the disc space between the vertebrae may help to regenerate the disc tissue. The rhGDF-5 used in the previous bone studies was in a solid form, and the rhGDF-5 that will be used in this study is in a liquid form, which is injected into your disc.
In the procedure you will undergo, an injection of either rhGDF-5 or a placebo (same fluid without the active ingredient) will be administered into the disc, which is the space between two vertebrae (bones in your spine).
Approximately 45 subjects will be enrolled into the study at up to 15 research sites. Enrollment for this study is now open at the Hospital for Special Surgery. If you agree to participate and meet the study requirements, you will be randomly assigned by chance to receive either the placebo or rhGDF-5 (at a dose of 1.0 mg or 2.0 mg). Random assignment will continue for up to 45 subjects unless there is a safety concern. There is a 2 out of 3 chance that you will receive the study drug (rhGDF-5 at either 1.0 mg or 2.0 mg) and a 1 out of 3 chance that you will receive the placebo. Approximately 30 subjects total will participate in the active study drug arm of the study and 15 subjects will be in the placebo arm of the study. Once you reach the 6-month follow up visit, your study drug will be un-blinded to determine whether you received the study drug (rhGDF-5) or the placebo. If you received the placebo, your current health status will be re-evaluated to check that there have been no significant changes that may contraindicate study treatment with rhGDF-05. If no significant changes have occurred, you will be offered the opportunity to receive the study drug (at 1.0 mg) and start the study again, beginning at visit 2.
If you are enrolled into the study, your participation is expected to last 36 months (or 42 months if you received placebo and decide to receive the study drug after your 6-month follow-up visit). You will have at least 7 visits to the research center (or 11), including the study visit(s) when you receive either the study drug or the placebo.
Inclusion - Candidates must meet ALL of the following:
1. Persistent low back pain with at least 3 months of non-surgical therapy at one symptomatic lumbar level (L3/L4 to L5/S1) as confirmed using a standardized provocative discography protocol. The required discography protocol will be provided by the sponsor. Subjects with multilevel disease must have a provocative discogram confirming that only one level is symptomatic at least two weeks prior to administration. Historical provocative discograms may be used for diagnostic purposes, with an expiry of 12 calendar months from the date performed. If the study treatment is not performed within those 12 calendar months, a new discogram will be required.
2. Oswestry Disability Index (ODI) for low back pain of 30 or greater
3. Low Back Pain score greater than or equal to 4 cm as measured by Visual Analog Scale (VAS) at Visit 1 Baseline
4. Male or Female 18 years of age or older
5. A signed IRB-approved Informed Consent Form (ICF)
6. Able to meet the protocol follow-up schedule and activities
7. Females of childbearing potential must have a negative urine pregnancy test at screening (Baseline Visit) and on the day of first administration prior to injection, and on the day of the second administration prior to injection, if participating in the open access arm of the study.
Exclusion - Candidates will be excluded if they meet ANY of the following:
1. Persons unable to have a discogram, CT or MRI (Magnetic Resonance Imaging)
2. Abnormal neurological exam at baseline (e.g., chronic radiculopathy)
3. Active radicular pain due to anatomical compression such as stenosis or disc herniation
4. Extravasation of contrast agent during the discogram, into the epidural space (does not include leak of contrast agent along the needle track or leakage to the outer annular ring at the posterior longitudinal ligament vicinity)
5. Suspected symptomatic facet joints and/or severe facet joint degeneration at the index level or adjacent segments
6. Suspected symptomatic sacro-iliac joint
7. MRI findings demonstrate any of the following:
Suspected disc appears normal
>50% decrease in disc height
Modic II and III changes, (Modic Type I is acceptable) and/or
Presence of suspected symptomatic osteophytes or significant suspected symptomatic facet arthrosis
8. Any prior lumbar spinal surgeries at suspected symptomatic level; prior surgery at the adjacent levels is acceptable except for fusion or arthroplasty surgery
9. Presence of spondylolisthesis (anterolisthesis or retrolisthesis)
10. Symptomatic disc degeneration at more than 1 lumbar level. (Multi-level disc degeneration based on MRI findings is acceptable, but only the symptomatic level may be treated.)
11. Evidence of active infection
12. Immunosuppressive therapy within 3 months
13. Long-term steroid (greater than 6 months) use. Inhaled steroids are acceptable.
14. Previous exposure to any bone morphogenetic protein (including rhGDF-5)
15. Tumor in the spine
16. Persons with any form of cancer (past or present)
17. Non-contained herniated nucleus pulposus
18. Any prior intradiscal therapies (chemonucleolysis, IDET, intradiscal steroid injection) at the same level being treated.
19. Any non-intradiscal steroid injection less than 2 months prior to administration. Does not include isolated joint injections outside the lumbar region
20. Nerve block injection less than 2 months prior to injection (nerve blocks may be performed for diagnostic purposes)
21. Known autoimmune disease
22. Type I Insulin-dependent diabetes mellitus (Type II, non-insulin dependent diabetes mellitus is allowed.)
23. Pregnant or lactating, or wishes to become pregnant within the first 12 months following each study treatment injection
24. Involved in pending litigation of the spine (including all workmen’s compensation cases that are unresolved)
25. Demonstrates signs of non-organic pain (e.g., Waddell’s Signs)
26. Based on clinical history, physical examination and subject presentation, subject has, or is suspected to have, a history of alcohol and/or drug abuse that would preclude subject from providing adequate consent and/or complying with study requirements
28. Morbid Obesity, defined as Body Mass Index (BMI) greater than 40
29. Life expectancy less than 2 years
30. Enrolled in another interventional clinical study
31. Any significant psychological disturbance, past or present, that could impair the consent process or ability to complete subject self-report questionnaires
Josh D. Back
Gregory E. Lutz