Early Lumbar Disc Degeneration
Conditions
Brief summary
Study to show the safety, tolerability and preliminary effectiveness of Intradiscal rhGDF-5 in subjects with early lumbar disc degeneration.
Interventions
The API is recombinant human growth and differentiation factor-5 (rhGDF-5), a recombinant version of human GDF-5. GDF-5 is a member of the transforming growth factor-b (TGF-b) superfamily and the bone morphogenetic protein (BMP) subfamily, and is known to influence the growth and differentiation of various tissues, including the intervertebral disc. In vitro experiments have shown that rhGDF-5 can stimulate gene expression and synthesis of the extracellular matrix proteins type II collagen and aggrecan. In vivo experiments in rabbit models of disc degeneration have shown that intradiscal injections of rhGDF-5 can stimulate an increase in disc height and hydration.
Sponsors
Janssen-Cilag Pty Ltd
DePuy Spine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Persistent low back pain with at least 3 months of non-surgical therapy at one or two suspected symptomatic lumbar levels (L3/L4 to L5/S1) a. The recruiting physician will use their standard clinical and radiological practice to determine the one/two disc level(s) be treated, i.e., but not limited to a combination of MRI, CT and/or Technetium bone scans, functional x-rays, input from a spinal injection program (targeting facet joints and/or epidural space) and discography (a discogram performed within 12 months of the anticipated study treatment date is acceptable, as long as the subject has not had an accident or re-injury). 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
Exclusion criteria
1. Persons unable to have an MRI 2. Abnormal neurological exam at baseline (e.g., chronic radiculopathy) 3. Persons with neurological or radiographic evidence of active radicular pain due to anatomical compression such as stenosis or disc herniation (persons with somatic referred pain are allowed) 4. Suspected symptomatic facet joints and/or severe facet joint degeneration at the index level(s) or adjacent segments 5. Suspected symptomatic sacro-iliac joint
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurological Assessment for Motor Function and Reflexes/Sensory | 12 months | Neurological Assessment for Motor Function and Reflexes/Sensory- Number of patients with Clinically Significant Abnormal results at 12 months. For Motor Function, Clinically Significant Abnormal results are determined by the surgeon investigator and are further classified by grade: 0= No Movement, 1= Flicker/trace of contraction, 2=Active movement when gravity removed, 3= Active movement against gravity, 4= Active Movement against gravity and resistance. For Reflexes/Sensory, Clinically Significant Abnormal results are determined by the surgeon investigator and are based on exams of the Knee, Ankle, L3-L5 Dermatone, and S1 Dermatome. Tension signs are evaluated with a straight leg raise to determine at which point, if any, sciatic pain occurs. |
| Treatment Emergent Adverse Events- Relationship to Study Drug | Through a 12 month period and annual telephone contact at 24 and 36 months for subject health status follow-up. | Number of patients with Treatment Emergent Adverse Events that were designated as related or possibly related to Study Drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Function Assessed by Oswestry Disability Index Change at 12 Months From Baseline | 12 months | The Oswestry Disability Index (ODI) is a 10-category (Pain Intensity, Personal Care, Lifting, Walking, Sitting, Standing, Sleeping, Sex Life, Social Life, Traveling) disability measurement scale with a graded response from 0 to 5, with 0 being the best score (no impairment) to 5 being the worst score (significant impairment). ODI score for a subject is calculated by adding the scores and converting the score to a 100 point scale. |
| Change in Pain Visual Analog Scale (VAS) at 12 Months From Baseline. | 12 months | The Visual Analog Scale (VAS) pain score asks the subject to place a vertical mark on a horizontal line (that is approximately 10 cm long) with 'No Pain' (score of 0 = 0 cm) listed on the left and 'Very severe pain' (score of 10=10cm) labeled on the right. The subject is instructed to indicate the amount of pain they feel in their back. |
| Change in Physical Component Summary of Quality of Life Measure Assessed by Short-Form 36 at 12 Months From Baseline. | 12 Months | The 36-item Short Form Health Survey (SF-36) is a patient reported outcome survey that evaluates functional health and well-being. The survey is converted into two summary measures (the Physical Component - PCS and Mental Component- MCS) that are scored from 0 to 100 (where 100 indicates the highest level of health). |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intradiscal rhGDF-5 (1.0mg) The API is recombinant human growth and differentiation factor-5 (rhGDF-5), a recombinant version of human GDF-5. GDF-5 is a member of the transforming growth factor-b (TGF-b) superfamily and the bone morphogenetic protein (BMP) subfamily, and is known to influence the growth and differentiation of various tissues, including the intervertebral disc. | 14 |
| Intradiscal rhGDF-5 (2.0mg) The API is recombinant human growth and differentiation factor-5 (rhGDF-5), a recombinant version of human GDF-5. GDF-5 is a member of the transforming growth factor-b (TGF-b) superfamily and the bone morphogenetic protein (BMP) subfamily, and is known to influence the growth and differentiation of various tissues, including the intervertebral disc. | 26 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Intradiscal rhGDF-5 (1.0mg) | Intradiscal rhGDF-5 (2.0mg) | Total |
|---|---|---|---|
| Age, Continuous | 44.2 years STANDARD_DEVIATION 10.85 | 48.3 years STANDARD_DEVIATION 10.37 | 46.9 years STANDARD_DEVIATION 10.59 |
| Region of Enrollment Australia | 14 participants | 26 participants | 40 participants |
| Sex: Female, Male Female | 8 Participants | 11 Participants | 19 Participants |
| Sex: Female, Male Male | 6 Participants | 15 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 14 | 18 / 26 |
| serious Total, serious adverse events | 1 / 14 | 4 / 26 |
Outcome results
Primary
Neurological Assessment for Motor Function and Reflexes/Sensory
Neurological Assessment for Motor Function and Reflexes/Sensory- Number of patients with Clinically Significant Abnormal results at 12 months. For Motor Function, Clinically Significant Abnormal results are determined by the surgeon investigator and are further classified by grade: 0= No Movement, 1= Flicker/trace of contraction, 2=Active movement when gravity removed, 3= Active movement against gravity, 4= Active Movement against gravity and resistance. For Reflexes/Sensory, Clinically Significant Abnormal results are determined by the surgeon investigator and are based on exams of the Knee, Ankle, L3-L5 Dermatone, and S1 Dermatome. Tension signs are evaluated with a straight leg raise to determine at which point, if any, sciatic pain occurs.
Time frame: 12 months
Population: Safety Population~The Neurological Assessment at 12 months was only conducted on 13 subjects from the 1.0mg group (out of 14 total subjects) and 25 subjects from the 2.0 mg group (out of 26 total).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intradiscal rhGDF-5 (1.0mg) | Neurological Assessment for Motor Function and Reflexes/Sensory | 0 participants |
| Intradiscal rhGDF-5 (2.0mg) | Neurological Assessment for Motor Function and Reflexes/Sensory | 2 participants |
Primary
Treatment Emergent Adverse Events- Relationship to Study Drug
Number of patients with Treatment Emergent Adverse Events that were designated as related or possibly related to Study Drug.
Time frame: Through a 12 month period and annual telephone contact at 24 and 36 months for subject health status follow-up.
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intradiscal rhGDF-5 (1.0mg) | Treatment Emergent Adverse Events- Relationship to Study Drug | 2 participants |
| Intradiscal rhGDF-5 (2.0mg) | Treatment Emergent Adverse Events- Relationship to Study Drug | 1 participants |
Secondary
Change in Function Assessed by Oswestry Disability Index Change at 12 Months From Baseline
The Oswestry Disability Index (ODI) is a 10-category (Pain Intensity, Personal Care, Lifting, Walking, Sitting, Standing, Sleeping, Sex Life, Social Life, Traveling) disability measurement scale with a graded response from 0 to 5, with 0 being the best score (no impairment) to 5 being the worst score (significant impairment). ODI score for a subject is calculated by adding the scores and converting the score to a 100 point scale.
Time frame: 12 months
Population: FAS Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intradiscal rhGDF-5 (1.0mg) | Change in Function Assessed by Oswestry Disability Index Change at 12 Months From Baseline | -13.0 units on a scale | Standard Deviation 14.63 |
| Intradiscal rhGDF-5 (2.0mg) | Change in Function Assessed by Oswestry Disability Index Change at 12 Months From Baseline | -18.1 units on a scale | Standard Deviation 13.69 |
Secondary
Change in Pain Visual Analog Scale (VAS) at 12 Months From Baseline.
The Visual Analog Scale (VAS) pain score asks the subject to place a vertical mark on a horizontal line (that is approximately 10 cm long) with 'No Pain' (score of 0 = 0 cm) listed on the left and 'Very severe pain' (score of 10=10cm) labeled on the right. The subject is instructed to indicate the amount of pain they feel in their back.
Time frame: 12 months
Population: FAS Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intradiscal rhGDF-5 (1.0mg) | Change in Pain Visual Analog Scale (VAS) at 12 Months From Baseline. | -2.66 units on a scale | Standard Deviation 3.448 |
| Intradiscal rhGDF-5 (2.0mg) | Change in Pain Visual Analog Scale (VAS) at 12 Months From Baseline. | -3.80 units on a scale | Standard Deviation 2.651 |
Secondary
Change in Physical Component Summary of Quality of Life Measure Assessed by Short-Form 36 at 12 Months From Baseline.
The 36-item Short Form Health Survey (SF-36) is a patient reported outcome survey that evaluates functional health and well-being. The survey is converted into two summary measures (the Physical Component - PCS and Mental Component- MCS) that are scored from 0 to 100 (where 100 indicates the highest level of health).
Time frame: 12 Months
Population: FAS Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intradiscal rhGDF-5 (1.0mg) | Change in Physical Component Summary of Quality of Life Measure Assessed by Short-Form 36 at 12 Months From Baseline. | 11.18 units on a scale | Standard Deviation 13.206 |
| Intradiscal rhGDF-5 (2.0mg) | Change in Physical Component Summary of Quality of Life Measure Assessed by Short-Form 36 at 12 Months From Baseline. | 10.00 units on a scale | Standard Deviation 9.897 |