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.
DRUGVehicle control
Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection
Sponsors
Janssen Korea, Ltd., Korea
DePuy Spine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
DOUBLE (Subject, Investigator)
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 suspected symptomatic lumbar level (L3/L4 to L5/S1) as confirmed using a standardized discography protocol. The required discography protocol will be provided by the sponsor. Subjects with multilevel disease must have a provocative discogram confirming that only 1 level is symptomatic at least 2 weeks prior to administration, with an expiry of 12 months from the date performed. 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 a discogram, CT, or MRI 2. Abnormal neurological exam at baseline (e.g., chronic radiculopathy) 3. Active radicular pain due to anatomical compression such as stenosis or disc herniation (radicular pain is defined as pain below the knee) 4. Extravasation of contrast agent during the discogram into the epidural space (does not include leakage 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
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 Definitely Related to Study Drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Function Assessed by Oswestry Disability Index Change at 12 Months From Baseline. | 12 month | 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). |
| Change in Mental Component Summary Quality of Life Measure Assessed by Short Form SF-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
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intradiscal rhGDF-5 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. | 22 |
| Vehicle Control Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection
Vehicle control: Excipients in Intradiscal rhGDF-5, to include Trehalose, Glycine, HCl, and Water for Injection | 9 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Intradiscal rhGDF-5 | Vehicle Control | Total |
|---|---|---|---|
| Age, Continuous | 41.4 years STANDARD_DEVIATION 11.78 | 40.6 years STANDARD_DEVIATION 15.63 | 41.2 years STANDARD_DEVIATION 12.74 |
| Region of Enrollment Korea, Republic of | 22 participants | 9 participants | 31 participants |
| Sex: Female, Male Female | 10 Participants | 3 Participants | 13 Participants |
| Sex: Female, Male Male | 12 Participants | 6 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 22 | 5 / 9 |
| serious Total, serious adverse events | 5 / 22 | 2 / 9 |
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~For the Neurological Assessment at 12 months, only 21 subjects from the rhGDF-5 group completed the assessment (out of 22 total subjects) and 5 subjects from the Control group completed the assessment (out of 9 subjects total).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intradiscal rhGDF-5 1.0mg | Neurological Assessment for Motor Function and Reflexes/Sensory | 0 participants |
| Vehicle Control | Neurological Assessment for Motor Function and Reflexes/Sensory | 0 participants |
Primary
Treatment Emergent Adverse Events- Relationship to Study Drug
Number of patients with Treatment Emergent Adverse Events that were designated as Definitely 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 | 0 participants |
| Vehicle Control | Treatment Emergent Adverse Events- Relationship to Study Drug | 0 participants |
Primary
Treatment Emergent Adverse Events- Relationship to Study Drug
Number of patients with Treatment Emergent Adverse Events that were designated as Possibly or Probably Related to Study Drug.
Time frame: 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 | 0 participants |
| Vehicle Control | 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 month
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. | -13.5 units on a scale | Standard Deviation 13.86 |
| Vehicle Control | Change in Function Assessed by Oswestry Disability Index Change at 12 Months From Baseline. | -10.4 units on a scale | Standard Deviation 8.98 |
Secondary
Change in Mental Component Summary Quality of Life Measure Assessed by Short Form SF-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~Only 21 subjects from the rhGDF-5 group (out of 22 subjects total) completed the MCS, SF-36.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intradiscal rhGDF-5 1.0mg | Change in Mental Component Summary Quality of Life Measure Assessed by Short Form SF-36 at 12 Months From Baseline. | 4.03 units on a scale | Standard Deviation 14.05 |
| Vehicle Control | Change in Mental Component Summary Quality of Life Measure Assessed by Short Form SF-36 at 12 Months From Baseline. | 4.34 units on a scale | Standard Deviation 10.727 |
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. | -2.49 units on a scale | Standard Deviation 2.211 |
| Vehicle Control | Change in Pain Visual Analog Scale (VAS) at 12 Months From Baseline. | -1.42 units on a scale | Standard Deviation 3.177 |
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~Only 21 subjects from the rhGDF-5 group (out of 22 total subjects) completed the baseline PCS, SF-36.
| 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 | 2.52 units on a scale | Standard Deviation 7.354 |
| Vehicle Control | Change in Physical Component Summary of Quality of Life Measure Assessed by Short Form 36 at 12 Months From Baseline | 3.24 units on a scale | Standard Deviation 9.879 |