Intradiscal rhGDF-6 for the Treatment of Lumbar Disc Degeneration

Official title

A Phase I/II, Open-label, Single Administration Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Efficacy of Intradiscal rhGDF-6 for the Treatment of Lumbar Disc Degeneration

Overview

The goal of this clinical trial is to find out if a new medicine can help people who have long-lasting back pain caused by damaged spinal discs. The study will also check if the medicine is safe to use. The main questions this study aims to answer are: Is the medicine safe, and what amount works best? Can it reduce long-term back pain? Researchers will test a medicine called CBT005, which contains a healing protein, by injecting it into the spinal discs. They will watch closely to see how people respond to the treatment. Participants will: Receive one study injection into the spinal disc Visit the clinic in person during the first 12 months for checkups Receive phone calls at 24 and 36 months to see how they are doing Still be able to get other pain treatments in the future, including surgery, if needed

Interventions

• Biological High Dose
  High Dose: 4 mg dose of Growth differentiation factor 6
• Biological Low Dose
  Low dose: 2mg dose of Growth differentiation factor 6

Primary outcome measures

• Neurological Status [Time frame: From enrollment through to 12 months]
• Oswestry Disability Index (ODI) [Time frame: Enrollment through to 12 months]

Secondary outcome measures (2)

• Visual Analog Scale [Time frame: From enrollment through to 12 months]
• EQ5D-5L [Time frame: From enrollment through to 12 months]

Eligibility criteria

Inclusion criteria

• Persistent low back pain, with at least 3 months of non-surgical therapy, at one symptomatic disc or two symptomatic lumbar disc levels (from L2 to S1).
• MRI scans show Pfirrmann disc degeneration grade 2 to 4 or High Intensity Zone (HIZ) signal change with or without Modic endplate changes.
• Symptoms are a fair bit or a lot bothersome, which require medication or other types of treatments or very disrupting (in response to question\*).
• Preoperative Oswestry Disability Index (ODI) score greater than or equal to 30%
• Visual Analog Score for back pain ≥40 mm.
• Any gender, 18 years of age or older
• Clinician diagnosed discogenic pain
• A signed HREC-approved Informed Consent Form
• Able to meet the protocol follow-up schedule and activities
• Females of childbearing potential must have a negative urine/serum pregnancy test at screening (Baseline Visit) and on the day of administration prior to injection \*Question defined in full protocol

Exclusion criteria

• People unable to have an MRI
• Abnormal neurological exam at baseline (e.g., chronic radiculopathy)
• Active radicular pain due to anatomical compression such as stenosis or disc herniation
• Symptomatic facet joints and/or severe facet degeneration at the index level or adjacent segments
• Symptomatic Sacro-iliac joint
• MRI findings demonstrate any of the following: Suspected disc appears normal or >50% decrease in disc height or Presence of symptomatic osteophytes
• Any prior lumbar spinal surgeries at suspected symptomatic level; prior surgery at the adjacent levels is acceptable including fusion or arthroplasty, provided the said adjacent level is not independently symptomatic.
• Presence of spondylolisthesis (anterolisthesis, retrolisthesis is acceptable)
• Symptomatic disc degeneration at more than 2 lumbar levels (multi-level disc degeneration based on MRI findings is acceptable with up to two symptomatic level. Only the symptomatic levels will be treated)
• Evidence of active infection
• Immunosuppressive therapy within 3 months prior to investigational product administration
• Either continuous or cumulative use of more than 2 months use in the past 6 months of an oral or systemic steroid. Inhaled steroids are acceptable
• Tumor in the spine
• People with any current and previous cancer. An exemption to this is previous BCCs which have been successfully removed.
• Non-contained herniated nucleus pulposus
• Any prior intradiscal therapies (chemonucleolysis, IDET, intradiscal steroid injection) at the same level being treated, other than rhGDF-6.
• Any non-intradiscal steroid injection less than 2 months prior to administration. Does not include isolated joint injections outside the lumbar region.
• Nerve block injection less than 2 months prior to injection of study medication.
• Known autoimmune disease
• Type 1 Insulin-dependent diabetes mellitus (Type II, non-insulin dependent diabetes mellitus is allowed)
• Pregnant or lactating, or wishes to become pregnant within the first 12 months of the study
• Involved in pending litigation of the spine (including workers compensation cases)
• Demonstrates signs of non-organic pain (e.g., Waddell's Signs)
• Based on clinical history, physical examination and participant presentation, participant has, or is suspected to have, a history of alcohol and/or drug abuse that would preclude participants from providing adequate consent and/or complying with study requirements
• Prisoner
• Morbid Obesity, defined as Body Mass Index (BMI) ≥40
• Life expectancy less than 2 years
• Any significant psychological disturbance past or present, that could impair the consent process or ability to complete participant self-report questionnaires
• Any reason not cited above that, in the opinion of the Principal Investigator, would pose a risk to either the participant or to the integrity of the clinical trial

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 1 center

• Spine & Scoliosis Service — Kogarah

Publications

• Wei A, Williams LA, Bhargav D, Shen B, Kishen T, Duffy N, Diwan AD. BMP13 prevents the effects of annular injury in an ovine model. Int J Biol Sci. 2009 Jun 3;5(5):388-96. doi: 10.7150/ijbs.5.388. PMID 19521550
• Miyazaki S, Diwan AD, Kato K, Cheng K, Bae WC, Sun Y, Yamada J, Muehleman C, Lenz ME, Inoue N, Sah RL, Kawakami M, Masuda K. ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model. Eur Spine J. 2018 Apr;27(4):739-751. do PMID 29460012

Identifiers

NCT: NCT07668466 · 001-CBT-005 Intradiscal rhGDF6

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗